Published online Sep 26, 2026. doi: 10.5494/wjh.121043
Revised: April 29, 2026
Accepted: May 18, 2026
Published online: September 26, 2026
Processing time: 192 Days and 13.8 Hours
Hypertension is a chronic medical condition characterized by persistently elevated arterial blood pressure (BP) and represents one of the leading global risk factors for cardiovascular morbidity and mortality. Prognostic markers are de
Core Tip: The present review provides an updated and comprehensive overview of the fundamental role of various prognostic markers, including C-reactive protein, neutrophil-to-lymphocyte ratio, microalbuminuria, N-terminal pro-B-type natriuretic peptide, carotid intima-media thickness, glomerular filtration rate, triglycerides, body mass index, total cholesterol, fasting plasma glucose, right atrial pressure, and mixed venous oxygen saturation, involved in the pathogenesis of hypertension.
- Citation: Rafaqat S. Role of prognostic markers in the pathogenesis of hypertension. World J Hypertens 2026; 12(1): 121043
- URL: https://www.wjgnet.com/2220-3168/full/v12/i1/121043.htm
- DOI: https://dx.doi.org/10.5494/wjh.121043
Hypertension (high blood pressure [BP]) is the main risk factor for adult mortality and cardiovascular disease, with a prevalence of 31.1% globally[1]. The most common avoidable cause of cardiovascular death and disease burden worldwide is hypertension[2,3]. One aspect that determines arterial pressure in resistive arteries is the arterial capacity. Patients with hypertension have a reduction in artery diameter due to structural, mechanical, and functional alterations. Systolic BP (SBP), pulse pressure, and artery stiffness are all increased by these modifications[4,5]. Hypertension is classified into several kinds based on its causes, severity, and the specific patterns of BP readings in the body. It is generally divided into two main categories: Primary (essential) hypertension and secondary hypertension. Pulmonary hypertension (PH), portal hypertension, and gestational hypertension/preeclampsia are examples of specialized hypertension. Pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH) are distinct forms of PH sharing similar symptoms such as shortness of breath, fatigue, and chest pain, which are due to elevated BP in the lung vessels. CTEPH is caused by organized, chronic blood clots blocking pulmonary arteries, while PAH involves the narrowing of small arteries.
Due to the significant impact of urbanization and lifestyle modifications on its underlying risk factors, the prevalence of hypertension will be significantly greater in emerging nations in the future years. Furthermore, there is a severe underutilization of healthcare services in poor nations for the routine screening of patients with hypertension. Hypertension is one of the leading causes of cardiovascular disease, which accounts for around one-third of all fatalities worldwide. The development, progression, and complications of atherosclerosis in the form of cardiovascular illnesses are mostly caused by high BP, which starts a series of events in the arterial wall that include oxidative stress, inflammation, and endothelial dysfunction. To lessen the economic and social cost of sickness, both developed and developing countries must address this health issue with diverse and complex approaches[6].
Prognostic markers are defined as clinical, biochemical, histopathological, or molecular parameters that provide information regarding disease progression and clinical outcomes. Prognostic markers in hypertension play a crucial role in predicting cardiovascular risk and the development of target organ damage. Several clinical, biochemical, and metabolic indicators have been identified as important predictors of adverse outcomes. These include increased BP variability, elevated SBP and diastolic BP (DBP) levels, higher body mass index (BMI), and elevated fasting blood glucose. Evidence of target organ damage, such as left ventricular (LV) hypertrophy and microalbuminuria (MAU), also serves as a strong prognostic indicator in patients with hypertension. In addition, inflammatory markers, particularly an increased neutrophil-to-lymphocyte ratio (NLR), along with hormonal alterations such as reduced testosterone levels, have been associated with worse cardiovascular outcomes. Components of metabolic syndrome, including dyslipidemia and insulin resistance, further contribute to the overall cardiovascular risk profile in individuals with hypertension[7,8]. Prognostic markers provide information regarding disease progression and clinical outcomes. In the context of hypertension, prognostic markers are crucial for cardiovascular risk stratification, early detection of target organ damage, and prediction of adverse events such as stroke and myocardial infarction. The present review provides an updated and comprehensive overview of the fundamental role of various prognostic markers involved in the pathogenesis and progression of hypertension. Although numerous prognostic indicators have been reported in the literature, this review specifically focuses on selected markers, including C-reactive protein (CRP), NLR, MAU, N-terminal pro-B-type natriuretic peptide (NT-proBNP), carotid intima-media thickness (CIMT), glomerular filtration rate (GFR), triglycerides (TG), BMI, total cholesterol (TC), fasting plasma glucose (FPG), right atrial pressure (RAP), and mixed venous oxygen saturation (SvO2). Table 1 explains the circulating levels of prognostic markers in patients with hypertension, whereas Table 2 reports the pathogenesis of these prognostic markers in patients with hypertension.
| Prognostic markers | Circulating levels |
| CRP | ↑ |
| NLR | ↑ |
| MAU | ↨ |
| NT-proBNP | ↑ |
| CIMT | ↑ |
| GFR | ↓ |
| TG | ↑ |
| BMI | ↑ |
| TC | ↑ |
| FPG | ↑ |
| RAP | ↑ |
| SvO2 | ↓ |
| Prognostic markers | Pathogenesis in hypertension |
| CRP | CRP is an acute-phase protein produced by the liver in response to inflammatory cytokines |
| CRP is one of the inflammatory indicators that are linked to hypertension | |
| In hypertension, CRP serves not only as a marker of inflammation but also contributes directly to vascular dysfunction | |
| CRP levels are linked to arterial stiffness, atherosclerosis, end-organ damage, and cardiovascular events in people with hypertension | |
| A direct and active role of CRP in the development of arterial stiffness, endothelial dysfunction, and high blood pressure | |
| Additionally, CRP has been linked to cardiac remodeling in response to pressure overload and vascular remodeling in reaction to injury | |
| One of the arterial alterations seen in animal models of hypertension is vessel wall inflammation | |
| The intricate processes that result in endothelial dysfunction, elevated peripheral vascular resistance, and major artery stiffness in hypertension are mediated by CRP | |
| There is no direct correlation between circulating CRP levels and hypertension or its consequences | |
| Nevertheless, increased CRP may suggest a causative pathway by which cumulative hemodynamic and non-hemodynamic effects cause cardiovascular illness, and inflammation is a component of the intricate pathophysiology connecting hypertension to vascular disease | |
| Reduced endothelium-dependent relaxation is associated with elevated CRP levels | |
| This endothelial dysfunction may worsen and eventually result in arterial wall lesions and atherosclerotic plaques | |
| Thus, CRP has been shown to have a causative role in the pathophysiology of hypertension and to be a validated risk assessment tool for coronary heart disease and stroke | |
| Vascular and cardiac remodeling in hypertension are significantly influenced by inflammation | |
| There was a substantial positive correlation between hypertension in the elderly and CRP, a measure of systemic inflammation | |
| Individuals with raised CRP had a much greater percentage of hypertension, coronary heart disease, and arthritis than those with normal CRP | |
| The development of hypertension may be postponed by early CRP detection and treatment | |
| The risk of hypertension and vascular damage are predicted by hs-CRP levels | |
| CRP directly causes endothelial dysfunction, which hinders blood vessel relaxation and raises blood pressure | |
| CRP contributes to the structural alterations in cardiac muscle (left ventricular hypertrophy) and blood vessels (vascular remodeling) brought on by pressure overload | |
| It is intimately associated with inflammation brought on by angiotensin II, which increases vascular resistance | |
| hs-CRP indicates the degree of subclinical inflammation | |
| Its effects are primarily driven through endothelial impairment, inflammation, oxidative stress, and neurohormonal activation, making it a valuable biomarker | |
| NLR | NLR is a simple marker of systemic inflammation derived from the balance between neutrophils (reflecting active inflammation) and lymphocytes (reflecting regulatory or protective immune responses), and it plays an important role in the pathogenesis of hypertension |
| A low-grade inflammatory marker | |
| This is reflected in NLR, which is calculated from ordinary blood counts; higher levels indicate more vascular inflammation | |
| An increased risk of hypertension is closely correlated with higher NLR scores | |
| Additionally, there is a favorable link between it and elevated systolic and diastolic blood pressure | |
| Elevated NLR is associated with the onset of left ventricular diastolic dysfunction in hypertensive patients and is greater in non-dipper patients (those whose blood pressure does not drop at night) than in dippers | |
| Compared to people with managed hypertension or normotension, patients with resistant hypertension have noticeably higher NLR levels | |
| Additionally, greater NLR levels were linked to higher degrees of diastolic dysfunction | |
| An elevated NLR indicates increased neutrophil-mediated inflammatory activity, which promotes endothelial dysfunction through the release of reactive oxygen species and proteolytic enzymes, leading to reduced nitric oxide availability and increased vascular stiffness | |
| At the same time, a relative reduction in lymphocytes reflects impaired immune regulation and heightened physiological stress, further amplifying inflammation | |
| This imbalance contributes to chronic low-grade vascular inflammation, enhanced vasoconstriction, and structural remodeling of blood vessels, ultimately resulting in sustained elevation of blood pressure and progression of hypertension | |
| MAU | MAU is associated with systemic low-grade inflammation and oxidative stress, indicating widespread vascular injury beyond the kidneys |
| In cases of essential hypertension, microalbuminuria is a powerful, independent predictor of cardiovascular death and morbidity | |
| It is linked to an increased risk of heart problems such left ventricular hypertrophy and shows early, frequently reversible, renal impairment | |
| Its presence indicates an early glomerular barrier collapse, frequently brought on by high blood pressure, which results in albumin leakage | |
| Greater blood pressure levels, poor blood pressure regulation (such as a non-dipping pattern), and a greater incidence of target-organ damage are all closely associated with it | |
| Individuals with microalbuminuria had a lower rate of creatinine clearance than individuals with normal UAE | |
| Microalbuminuria exhibit a range of biochemical and hormonal abnormalities with pathogenic potential, leading to a higher incidence of cardiovascular events and a higher decline in renal function in hypertensive patients compared to patients with normal UAE | |
| Microalbuminuria and LV mass were strongly positively correlated | |
| In individuals with hypertension, hypertensive retinopathy, regional wall motion abnormalities, and neurological deficiency have been identified as sensitive surrogate indicators for microalbuminuria | |
| Altogether, these mechanisms reflect generalized endothelial damage, increased vascular stiffness, and progressive target organ involvement, contributing to the development and worsening of hypertension | |
| NT-proBNP | Elevated NT-proBNP levels strongly suggest structural alterations such as left atrial enlargement or LV hypertrophy, as well as subclinical LV dysfunction |
| Chronic, high-level stimulation suggests a compensatory mechanism for prolonged, high wall stress (hypertension), even though it is typically released to cause vasodilation and natriuresis to drop blood pressure | |
| This implies that the pathophysiology of early-stage hypertension may entail reduced circulating BNP, which would lead to decreased vasodilation and natriuresis | |
| Serum log-NT-pro-BNP levels and endothelial dysfunction as assessed by vascular reactivity index values were shown to be negatively correlated in hypertensive individuals | |
| Higher NT-proBNP was linked to: Higher left ventricular mass index, left atrial volume index, lateral e′ velocity, E/e′ ratio, peak global longitudinal systolic strain, systolic strain rate, early diastolic strain rate | |
| CIMT | Hypertension-related structural vascular damage is indicated by elevated CIMT |
| It corresponds with other signs such as left ventricular hypertrophy and frequently signals more widespread, systemic damage | |
| Future cardiovascular events, such as myocardial infarction and stroke, can be strongly and independently predicted by elevated CIMT | |
| Thus, a thicker intima, media, or both may be the cause of an elevated CIMT | |
| While hypertrophy of the media layer is mostly associated with hypertension unrelated to atherosclerosis, processes involved in intimal thickening are considered to resemble those in the etiology and evolution of atherosclerotic plaques | |
| An elevated CIMT is believed to primarily indicate intimal rather than medial thickening since the elastic carotid artery has a comparatively small media in comparison to muscular arteries, even if thickening of the intima and media can occur through different pathways | |
| Increased IMT is strongly associated with hypertension, indicating that artery wall thickening is a result of elevated blood pressure | |
| Hypertension had greater rates of aberrant common carotid artery intima-media thickness and carotid plaques | |
| GFR | Reduced afferent arteriole resistance in early hypertension can raise glomerular capillary pressure, which results in hyperfiltration (high GFR) |
| Long-term high blood pressure eventually damages glomeruli structurally, which lowers GFR. The excretion of sodium depends on GFR | |
| In order to maintain equilibrium, salt is retained if GFR does not rise in tandem with factors like angiotensin II, which raises blood pressure | |
| In addition to being a result of renal failure, hypertension also contributes to cardiovascular problems because pressure damages the kidneys (lower GFR) | |
| In early hypertension, increased systemic and intraglomerular pressure may initially maintain or even elevate GFR (hyperfiltration), but this comes at the cost of damage to the delicate glomerular capillaries | |
| Over time, sustained high pressure, along with activation of the renin-angiotensin-aldosterone system, leads to endothelial injury, inflammation, and fibrosis within the kidneys, causing a gradual decline in GFR | |
| Reduced GFR results in impaired sodium and fluid excretion, leading to volume expansion and further elevation of blood pressure | |
| Additionally, declining kidney function exacerbates vascular stiffness and hormonal dysregulation, creating a vicious cycle in which hypertension worsens renal damage, and renal impairment further sustains and aggravates hypertension | |
| TG | Elevated triglycerides cause oxidative stress and hinder endothelial-dependent vasodilation, which prevents blood vessels from fully relaxing |
| Increased blood viscosity, or thickness, caused by elevated triglycerides impairs blood flow and raises the strain on artery walls | |
| A major sign of insulin resistance, the underlying cause of both metabolic syndrome and high blood pressure, is elevated triglycerides, particularly when combined with low HDL cholesterol | |
| Peripheral vascular resistance rises when lipid levels are elevated because they cause or worsen arterial wall thickening and constriction | |
| TGs are linked to left ventricular mass in hypertensive individuals | |
| The TG and creatinine levels were positively correlated with the SBP, whereas the cholesterol level was positively correlated with the pulse pressure | |
| TG contribute to the development of hypertension primarily through their role in metabolic dysfunction and vascular injury | |
| Elevated triglyceride levels are associated with increased production of atherogenic lipoproteins, which promote endothelial dysfunction by reducing nitric oxide availability and increasing oxidative stress | |
| This leads to impaired vasodilation and increased vascular resistance. High TG levels are also linked to insulin resistance, which enhances sympathetic nervous system activity and renal sodium retention, both of which raise blood pressure | |
| In addition, triglyceride-rich particles can trigger low-grade inflammation and contribute to arterial stiffness and atherosclerosis | |
| Together, these mechanisms result in increased vascular tone, reduced arterial compliance, and sustained elevation of blood pressure in hypertension | |
| BMI | Increased visceral fat from an elevated BMI induces insulin resistance, activates the sympathetic nervous system, and causes the kidneys to retain salt, all of which raise blood pressure |
| For every unit increase in BMI, systolic blood pressure rises by about 2.0 mmHg for males and 1.4 mmHg for women | |
| Losing weight can dramatically lower systolic and diastolic blood pressure, which frequently eliminates the need for antihypertensive drugs | |
| BMI contributes to hypertension through multiple interrelated metabolic and hemodynamic mechanisms associated with excess adiposity | |
| Increased BMI reflects higher fat accumulation, which promotes insulin resistance and leads to activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system, resulting in vasoconstriction, sodium retention, and elevated blood pressure | |
| Adipose tissue also acts as an active endocrine organ, releasing inflammatory cytokines and adipokines that induce endothelial dysfunction by reducing nitric oxide availability and increasing oxidative stress | |
| Additionally, increased body mass raises cardiac output and blood volume, placing greater strain on the vascular system | |
| These combined effects lead to increased vascular resistance, arterial stiffness, and sustained elevation of blood pressure in individuals with higher BMI | |
| TC | Total cholesterol contributes to hypertension primarily through its role in vascular dysfunction and atherosclerosis |
| Atherosclerosis, which is brought on by cholesterol deposits (plaques), limits blood flow and decreases arterial flexibility, hence raising systolic blood pressure | |
| Although it is not the main cause of high blood pressure, elevated cholesterol plays a major role | |
| When combined, they significantly raise the risk of renal problems, heart attacks, and strokes | |
| Research indicates a favorable correlation between elevated systolic and diastolic blood pressure and both total and LDL (“bad”) cholesterol | |
| Arterial stiffness mediates about half of the increase in SBP that causes TC | |
| Cholesterol is a contributing factor to hypertension | |
| Blood pressure rises as a result of blood vessel blockage and stiffness brought on by cholesterol accumulation | |
| Elevated total cholesterol, particularly due to increased LDL, leads to lipid deposition within the arterial wall, promoting plaque formation and arterial narrowing | |
| This process impairs endothelial function by reducing nitric oxide availability and increasing oxidative stress, resulting in decreased vasodilation and increased vascular resistance | |
| Additionally, cholesterol accumulation induces low-grade inflammation and vascular stiffness, which further elevates blood pressure | |
| Over time, these changes reduce arterial compliance and increase systemic vascular resistance, contributing to the development and persistence of hypertension | |
| FPG | FPG contributes to hypertension through mechanisms linked to hyperglycemia and insulin resistance |
| Even in the prediabetes range, elevated FPG levels are independently linked to a higher risk of hypertension | |
| Because high blood sugar makes blood cells “sticky”, they accumulate on the walls of blood arteries, narrowing them and making the heart work harder | |
| Although it is still a major determinant for both, the association between FPG and blood pressure is frequently more noticeable in men | |
| Elevated fasting glucose impairs endothelial function by reducing nitric oxide availability and increasing oxidative stress, leading to diminished vasodilation and increased vascular resistance | |
| Insulin resistance further activates the sympathetic nervous system and the renin-angiotensin-aldosterone system, promoting vasoconstriction and sodium retention | |
| Chronic hyperglycemia also induces low-grade inflammation and glycation of vascular proteins, which stiffen arterial walls and reduce their elasticity | |
| Together, these effects result in increased vascular tone, arterial stiffness, and sustained elevation of blood pressure in hypertension | |
| RAP | RAP reflects central venous pressure and right heart filling status, and it becomes relevant in hypertension particularly when there is associated cardiac dysfunction or volume overload |
| Increased severity of pulmonary arterial hypertension, decreased exercise capacity, and mortality are all strongly correlated with elevated RAP | |
| The RV finds it difficult to empty when pulmonary pressure increases, which raises right atrial pressure | |
| Advanced illness and remodeling are indicated by elevated RAP and high RA volume (as measured by the RA volume index, or RAVI) | |
| Regardless of RA size or pressure, PAH impairs RA reservoir and passive conduit functions, which probably indicate right ventricular failure and overload | |
| Increasing RAP was linked to decreased exercise capacity, atrial or ventricular arrhythmias and HF hospitalization | |
| In individuals with essential hypertension, RA function deteriorates | |
| RV function alterations are linked to RA function in PAH | |
| Severe RV diastolic stiffness is linked to decreased RV active filling and higher vena cava backflow, despite increased RA stroke effort | |
| A significant drop in afterload, an increase in RV active filling, and a decrease in vena cava backflow were all associated with a decrease in end-diastolic elastance | |
| In individuals with significant RV diastolic stiffness, RA PV loops indicate atrioventricular uncoupling and exhibit increased RA stiffness | |
| Patients with precPH had hypertrophied isolated RA cardiomyocytes without any intrinsic sarcomeric alterations | |
| Interstitial and perivascular fibrosis are associated with decreased capillary density in end-stage precapillary pulmonary hypertension | |
| In chronic hypertension, sustained increased afterload can lead to ventricular remodeling and eventual diastolic dysfunction, which impairs cardiac filling and elevates right-sided filling pressures | |
| Elevated RAP indicates increased venous congestion and reduced right ventricular compliance, often linked with fluid retention and neurohormonal activation such as the renin-angiotensin-aldosterone system | |
| This contributes to further sodium and water retention, worsening volume overload and maintaining high blood pressure | |
| Additionally, elevated RAP is associated with systemic venous congestion and reduced effective forward flow, reflecting advanced hemodynamic compromise in complicated hypertension and its cardiovascular consequences | |
| SvO2 | SvO2 reflects the balance between oxygen delivery and tissue oxygen consumption, and it provides indirect insight into cardiovascular efficiency in hypertension |
| SvO2 is independently correlated with both mean pulmonary artery stroke volume and right atrial area | |
| SvO2 was strongly and inversely linked with both sPAP and PAWP | |
| Nevertheless, there was no significant correlation found between SvO2 and left ventricular end-diastolic pressure | |
| In normal physiology, SvO2 remains stable when cardiac output and tissue oxygen demand are balanced; however, in advanced or complicated hypertension, especially with cardiac dysfunction, reduced cardiac output and impaired tissue perfusion can alter this balance | |
| When oxygen delivery decreases due to reduced stroke volume or increased vascular resistance, tissues extract more oxygen, leading to a fall in SvO2 | |
| Conversely, in severe circulatory inefficiency or impaired oxygen utilization, SvO2 may appear relatively elevated despite poor tissue perfusion | |
| Overall, changes in SvO2 in hypertension reflect underlying, hemodynamic stress, reduced cardiovascular efficiency, impaired systemic perfusion, particularly in advanced disease states with end-organ involvement |
Current evidence supports the role of these biomarkers as indicators of inflammation, metabolic dysfunction, and target organ damage (TOD) in hypertension; however, their causal roles, standardization, and clinical utility remain inadequately defined, highlighting the need for large-scale, longitudinal, and mechanistic studies to translate these markers into effective tools for risk stratification and targeted management.
This review specifically focuses on selected markers, including CRP, NLR, MAU, NT-proBNP, CIMT, GFR, TG, BMI, TC, FPG, RAP, and SvO2 in the pathogenesis of hypertension.
The literature review was conducted using databases such as Science Direct, PubMed, and Google Scholar. The literature search was conducted until March 10, 2026, keywords such as hypertension, prognostic markers, CRP, NLR, MAU, NT-proBNP, and CIMT were employed.
The selection of literature was guided by predefined inclusion and exclusion criteria to ensure the relevance and quality of the studies incorporated into this review.
Peer-reviewed original research articles, systematic reviews, editorials, and meta-analyses published in English and available in full text through recognized databases were considered for inclusion. Although preference was given to more recent publications, no strict time restrictions were applied. The review primarily focused on studies investigating the role of prognostic markers in the pathogenesis of hypertension, particularly those addressing pathogenesis, clinical implications and future perspectives.
Non-peer-reviewed sources, such as commentaries or opinion pieces. Conference abstracts or case reports with insufficient data. Duplicate publications. Studies not directly related to the objectives of this review. The excluded criteria pertain to studies that specifically address different cardiovascular diseases.
An accurate assessment of the severity and prognosis of PAH is necessary for its practical therapy. Recent treatment recommendations recommend employing a variety of prognostic markers to guide management decisions since they are known to be connected with patient prognosis. The right ventricle’s reaction to an increased afterload is the biggest predictor of a patient’s symptoms and survival, even though pulmonary vasculopathy is a characteristic of PAH[9].
Therefore, measurements that capture right ventricular (RV) function offer the best potential to assess PAH severity. Understanding how the tests used in routine clinical practice relate to right heart function in patients with PAH and how to create and improve existing assessments to maximize evaluation of the disease state and progression are two challenges. Future studies on PAH should concentrate on the most effective ways to evaluate right heart function and which measurements, or combinations of measurements, offer the most pertinent data for each patient[9].
The majority of hypertension guidelines use different cut-off values to classify hypertension. Another study looked at the prognostic significance of Grades 1 (140-159 mmHg and/or 90-99 mmHg), 2 (160-179 mmHg and/or 100-109 mmHg), and 3 (≥ 180 mmHg and/or ≥ 110 mmHg). It monitored a sample of 3150 initially untreated patients with hypertension (mean age 50 years, 44% female) who had no prior cardiovascular illness for an average of 10 years. Every patient had diagnostic testing, including ambulatory BP (ABP) monitoring for 24 hours[10].
The average 24-hour BP was 137/87 mmHg, and the average clinic BP was 156/97 mmHg at admission. Grade 1 and Grade 2 event rates did not differ statistically (0.73 vs 0.95 per 100 patient-years, respectively; P = 0.06). In comparison to Grades 1 and 2, it was greater in Grade 3 (1.93 per 100 patient-years; P < 0.01). The excess risk in Grade 3 was no longer significant (hazard ratio [HR]: 1.25, 95% confidence interval [CI]: 0.87-1.78; P = 0.22) after adjustment for 24-hour ambulatory systolic BP (SBP), but the HR was not different between Grade 1 and Grade 2 (P = 0.27) and higher in Grade 3 than in Grade 1 (P < 0.01). The relative risk of cardiovascular events associated with hypertension Grades 1 and 2 did not significantly vary. On the other hand, a higher cardiovascular risk is predicted by Grade 3 (clinic BP ≥ 180/110 mmHg), which is linked to higher levels of 24-hour ambulatory BP[10].
High morbidity and mortality are characteristics of both PAH and CTEPH. To assess the prognostic value of inflammation-based hematologic indices, such as NLR, platelet-to-lymphocyte ratio (PLR), neutrophil-percentage-to-albumin ratio (NPAR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII), was investigated. NPAR and SII were linked to lower overall survival (log-rank P = 0.002 and P = 0.012, respectively), post-discharge mortality (NPAR odds ratio [OR] 1.181, 95%CI: 1.062-1.313; P = 0.002), and in-hospital mortality (OR: 1.129, 95%CI: 1.011-1.261; P = 0.031, P = 0.002; OR: 1.002)[7].
While NLR predicted higher in-hospital mortality, higher LMR was linked to lower in-hospital mortality (OR: 0.291, 95%CI: 0.108-0.790; P = 0.015). The greatest predictors in CTEPH were NLR and LMR, which were associated with increased post-discharge mortality (NLR OR: 1.289, 95%CI: 1.029-1.615; P = 0.027) and poorer survival (log-rank P = 0.007 and P = 0.044). The potential benefit of SII in PAH and the encouraging performance of NPAR in CTEPH are suggested by receiver operating characteristic (ROC) analysis[7].
ABP enhances cardiovascular risk stratification above and beyond conventional risk variables, such as office BP, according to a number of event-based cohort studies. The majority of these investigations were carried out on individuals with essential hypertension who were not receiving therapy at the time of ABP monitoring; other studies were carried out on individuals who were either poorly managed with treatment or in the general population[11].
These studies looked at ABP either as a continuous variable or using operational risk classifications. The observed ABP (systolic, diastolic, and pulse) was directly and independently correlated with cardiovascular risk, whereas the degree of BP decline from day to night was inversely correlated. Additionally, there was a clear correlation between cardiovascular risk and the discrepancy between the office BP prediction and the actual ABP measurement[11].
Two classifications based on arbitrary operational risk categories are white-coat hypertension vs ambulatory hypertension and dippers against nondippers. Regardless of the average ABP value over the course of the 24 hours, a blunted or nonexistent BP decrease from day to night, defined using ABP as a continuous variable or with operational criteria, was equally linked to a poorer result. All things considered, these studies show that ABP monitoring is especially useful for improving cardiovascular risk stratification in individuals with resistant hypertension and untreated office hypertension. ABP-focused intervention research is currently required[11].
Several important prognostic markers have been identified in patients with hypertension, which help in predicting disease progression, target organ damage, and cardiovascular outcomes. These markers can be categorized into hemodynamic, biochemical, inflammatory, metabolic, hormonal, and demographic factors. Hemodynamic parameters play a central role in prognosis. Increased BP variability, higher grades of hypertension, and an elevated resting heart rate are associated with a greater risk of cardiovascular morbidity and mortality. Markers of target organ damage are also significant prognostic indicators. The presence of MAU, LV hypertrophy (LVH), and increased pulse wave velocity (PWV) reflects structural and functional vascular changes and is strongly associated with adverse cardiovascular outcomes. Inflammatory indices have gained increasing attention in recent years. An elevated NLR reflects systemic inflammation and has been linked to increased mortality and functional impairment in hypertensive individuals. Cardiac biomarkers are also valuable in risk stratification of hypertension.
Elevated levels of BNP and NT-proBNP indicate cardiac stress and are associated with an increased risk of heart failure and other cardiovascular complications. Metabolic markers contribute significantly to prognosis. Abnormal metabolic profiles, including elevated fasting glucose, increased TG levels, and reduced high-density lipoprotein (HDL) cholesterol (HDL-C), are associated with a higher cardiovascular risk in patients with hypertension. Hormonal factors also play a role, as reduced testosterone levels have been linked to adverse cardiovascular outcomes and may contribute to the progression of hypertension.
Finally, clinical and demographic factors are important predictors. Obesity, particularly reflected by a high BMI, is a strong predictor of hypertension and related complications. Additionally, advanced age is a well-established risk factor for the development of hypertension and is associated with an increased likelihood of cardiovascular events.
One of the most well-known indicators of cardiovascular illness is CRP, the prototypical acute-phase reactant. In patients who are at intermediate risk, circulating levels of CRP are utilized therapeutically to anticipate the incidence of cardiovascular events and to help choose medications based on more precise risk assessment. CRP levels are linked to arterial stiffness, atherosclerosis, end-organ damage, and cardiovascular events in patients with hypertension. Research indicates that several anti-hypertensive drugs may reduce CRP levels without affecting BP[12].
CRP levels have been demonstrated in several cohorts to predict the onset of hypertension at follow-up in people who are normotensive at baseline. It is debatable whether genetic variability that affects circulating CRP levels independently of behavioral and environmental variables may also be utilized in a similar way to predict changes in BP and the onset of hypertension. CRP actively and directly contributes to the development of endothelial dysfunction, vascular stiffness, and high BP in addition to its function as a biomarker[12].
In several clinical contexts, mild increases in CRP concentration are predictive of myocardial infarction, stroke, and vascular mortality. The predictive value of CRP is complementary to that of BP measurements, despite the absence of specific evidence linking CRP levels to cardiovascular risk in patients with hypertension. Increased CRP levels have been linked to hypertension, according to recent epidemiological data, and there are hints that CRP may be a predictor of future hypertension. One of the arterial alterations seen in animal models of hypertension is vessel wall inflammation. The intricate processes that result in endothelial dysfunction, elevated peripheral vascular resistance, and major artery stiffness in hypertension are mediated by CRP[13].
CRP decreases endothelial nitric oxide bioactivity, increases the tissue uptake of modified low-density lipoprotein (LDL), and increases the expression of local endothelial cell surface adhesion molecules, monocyte chemotactic protein 1, endothelin 1, and plasminogen activator inhibitor-1. A reduction in endothelium-dependent relaxation is associated with elevated CRP levels. This endothelial dysfunction may worsen, resulting in arterial wall lesions and eventually atherosclerotic plaques[14,15].
Elevated CRP is linked to hypertension[16], and it also predicts future risk of hypertension in normotensive individuals[17]. Even in individuals who have not yet received medication, CRP is more closely associated with systolic and pulse pressure (PP) than with DBP. Elevated CRP also coincides with measurements of arterial wave reflection and stiffness[18], which may indicate underlying atherosclerosis[19]. The lack of LV hypertrophy in hypertensive persons is predicted by low CRP and normal BNP levels[20].
Although there is little clinical evidence linking inflammation with incident hypertension (IHT), hypertension is partially an inflammatory illness. To investigate the relationship between IHT and CRP levels, a measure of systemic inflammation. In all predefined subgroups examined, including those with extremely low baseline BP and those without conventional cardiovascular risk factors, CRP was substantially linked to an elevated risk of developing hypertension. When baseline BP was controlled for, and CRP was treated as a continuous variable, similar outcomes were seen. Future hypertension is linked to elevated levels of CRP, indicating that hypertension may be partially an inflammatory condition[17].
One widespread and independent risk factor for cardiovascular disease, particularly coronary artery disease (CAD), is hypertension. Based on the BP readings taken during the first evaluation and diagnosis, primary or essential hypertension can be further categorized. According to the findings of several past studies, the risk of complications does not correlate with the stage of hypertension. Therefore, to lower the related morbidity, it is essential to find a method for evaluating the risk of future cardiovascular problems in patients (both overt hypertensives and pre-hypertensives). The relevance of several inflammatory indicators as risk assessment tools in hypertension is now being investigated by experts worldwide[14].
High-sensitivity CRP (hs-CRP) is the most extensively investigated biomarker. Another study evaluated cardiovascular risk in individuals with essential hypertension by correlating hs-CRP levels with the stage of hypertension among participants. The untreated patient group demonstrated significantly elevated hs-CRP levels compared to the control group. Furthermore, comparative analysis between treated and untreated patients showed a significant reduction in hs-CRP levels following treatment. Collectively, these findings suggest that hs-CRP, as a marker of subclinical inflammation, may serve as a useful indicator for assessing both the risk of adverse cardiovascular outcomes and the therapeutic response in patients with essential hypertension. Thus, untreated individuals with hypertension exhibit markedly higher hs-CRP levels, which decline significantly with appropriate treatment[14].
Another study assessed the association between CRP and resting BP in a multiethnic cohort of men and women from the Multi-Ethnic Study of Atherosclerosis (MESA). Many researchers have found that those with hypertension have higher CRP levels. The incidence of hypertension varies significantly among ethnic groups. There are still important uncertainties about whether the association between CRP and hypertension is consistent across sex and ethnic divisions. CRP levels were measured at the baseline clinical assessment of the MESA participants (n = 6814). An SBP or DBP ≥ 140/90 mmHg or a self-reported history of hypertension and antihypertensive drug usage were considered indicators of hypertension, which was treated as a binary variable (yes/no). Participants with hypertension had a geometric mean CRP of 2.3 ± 0.07 mg/L, whereas those with normotension had a mean of 1.6 ± 0.07 mg/L (P < 0.0001). Regardless of sex, the percentage difference in CRP levels between hypertensives and normotensives was 13% in men and 13% in women[21].
Chinese individuals had the lowest CRP concentration but the most variance in CRP by hypertension status (24%), according to ethnic comparisons. Hispanics showed no discernible variation in CRP by hypertension status, while Caucasians and African Americans had 10% to 15% higher CRP levels. Inflammation and hypertension are independently associated in both men and women. There were clear ethnic group differences, with Chinese individuals showing the highest correlation and Hispanics showing no variation in CRP levels based on the hypertension condition[21].
It has been suggested that hypertension might be partially an inflammatory condition. On the other hand, there is a dearth of clinical evidence about the correlation between inflammation and the likelihood of hypertension. To ascertain the relationship between the likelihood of developing hypertension in patients without hypertension and serum hs-CRP, a measure of systemic inflammation was reported[22].
Prehypertensive people had substantially higher baseline hs-CRP levels than normotensive people. Older age, higher BMI, diabetes mellitus (DM), and SBP and DBP were all linked to the likelihood of developing hypertension in univariate analysis. Patients with IHT had substantially higher levels of hs-CRP. Both SBP and log-transformed hs-CRP were independent predictors of developing hypertension in multivariate analysis after controlling for confounding factors. This shows that there is a slight correlation between baseline hs-CRP levels and a higher chance of developing hypertension. According to these findings, inflammation may play a significant role in the development of hypertension[22].
CRP is recognized as a predictor of adverse cardiovascular outcomes; however, the effects of antihypertensive therapy on CRP levels remain largely uncertain. In the community-based biracial Genetic Epidemiology Network of Arteriopathy cohort, a cross-sectional analysis of CRP levels in individuals with primary hypertension was conducted using single-agent anti-hypertensive treatment[23].
Participants’ median levels of CRP varied: 0.40 mg/dL for those using diuretics, 0.34 mg/dL for those on calcium channel blockers, 0.25 mg/dL for those taking beta blockers, and 0.27 mg/dL for those taking renin-angiotensin-aldosterone system inhibitors. The group taking renin-angiotensin-aldosterone system inhibitors had an average CRP that was 20% lower than the group taking diuretics after multivariable correction, but there were no discernible differences between the other drug classes. CRP and heart rate were significantly correlated. Inflammation may be affected by the antihypertensive drug class, especially in renin-angiotensin-aldosterone system (RAAS) inhibitor users[23].
In the 21st century, hypertension has grown to be a significant health risk factor, particularly for the elderly. The inflammatory marker, such as CRP, is strongly linked to hypertension, and inflammation plays a role in the development of hypertension[24].
The group with increased CRP had considerably greater rates of hypertension, CAD, and joint reactive inflammation. Additionally, there was a significant correlation between elevated CRP and the use of alcohol, LDL cholesterol (LDL-C), and steroids. Elevated CRP was positively associated with hypertension, BMI, and diabetes, whereas statin use was negatively associated with hypertension[24].
Inflammation is important in every stage of the atherosclerotic process. A circulating indicator of inflammation, CRP is a potent independent predictor of cardiovascular events. Inflammation and hypertension are intimately related. Specifically, CRP appears to be associated with arterial stiffness measures, indicating a special relationship between SBP and CRP. Nevertheless, these observational studies are unable to offer any concrete proof of a cause-and-effect relationship[25].
Prospective studies may provide a more robust framework for elucidating the potential causal relationship underlying this association. However, the limited availability of long-term data precludes definitive conclusions. Moreover, there is a lack of prospective, placebo-controlled interventional studies demonstrating that pharmacological reduction of CRP levels can decrease the risk of developing hypertension. Although this remains an intriguing hypothesis, the causal link between inflammation and BP regulation is yet to be clearly established in the absence of such critical evidence[25].
There is new evidence linking atherosclerosis with inflammation. However, recent research has indicated that inflammation may play a part in people with CAD and arterial hypertension (AH). An elevated risk of hypertension has been retrospectively linked to higher levels of CRP, which is a common and readily detectable inflammatory marker for which clinical cut points have been suggested. Nevertheless, there is still much to learn about the connection between the risk of developing hypertension and other inflammatory indicators other than CRP. The development of cardiovascular disease (CVD) and the pathophysiology of hypertension are mainly related to the activation of the renin-angiotensin system (RAS)[26].
Angiotensin II is a proinflammatory mediator in addition to its influence on BP. By lowering vascular inflammation and remodeling, RAS antagonistic action may enhance cardiovascular outcomes beyond BP regulation. Overall, the impact on AH and CVD is not well understood. Another study sought to determine if systemic inflammation and CRP levels are connected to AH. It was discovered that 48% of patients with AH had higher CRP levels. CRP levels are linked to the development of AH in the future, suggesting that AH caused by atherosclerosis is a component of inflammatory disease[26].
hs-CRP can predict cardiovascular events and encourage atherosclerosis. Nevertheless, there is presently no information on how hypertension and hs-CRP together affect cardiovascular risk. A higher but nonsignificantly higher incidence of cardiovascular events and more serious coronary lesions were linked to increasing hs-CRP[27].
In comparison to the reference group with low hs-CRP and normotension, patients with high hs-CRP and normal BP, as well as patients with hypertension with any level of hs-CRP, had more severe coronary lesions when hypertension was included as a stratifying factor. However, only individuals with high hs-CRP and hypertension had a substantially higher risk of cardiovascular events when compared to the reference group. In patients with stable, recently diagnosed CAD, the combination of elevated hs-CRP and hypertension significantly enhanced the cardiovascular risk, suggesting that hs-CRP may be used as a marker for classification in high-risk patients[27].
Growing evidence points to a connection between vascular inflammation and BP. Among 15215 women who were monitored prospectively for a median of 8.1 years, the study looked at the association between BP, CRP and incident first cardiovascular events[28].
Women with BP < 120/75, 120 to 129/75 to 84, 130 to 139/85 to 89, 140 to 159/90 to 94, and ≥ 160/95 mmHg had median CRP values of 0.96 mg/L, 1.42 mg/L, 2.20 mg/L, 2.82 mg/L, and 3.34 mg/L, respectively, according to cross-sectional analyses. Baseline CRP levels were significantly predicted by increasing BP categories. Both rising BP categories and increased CRP levels (≥ 3 mg/L) were independent predictors of future cardiovascular events in prospective studies, and CRP had incremental prognostic significance at all BP levels. When comparing women with BP < 120/75 and CRP < 3 mg/L to those with BP ≥ 160/95 mmHg and CRP ≥ 3 mg/L, the adjusted HR was 8.31 (95%CI: 4.44-15.55; P < 0.0001). Participants were categorized into four groups based on their BP (< 130/85 or ≥ 130/85) and CRP levels (< 3 mg/L or ≥ 3 mg/L). Compared to the low CRP/Low BP reference group (HR: 1.0), the risk-adjusted HRs increased progressively: 1.87 for high CRP/Low BP (P = 0.002), 2.54 for low CRP/high BP (P < 0.0001), and 3.27 for high CRP/high BP (P < 0.0001)[28].
Elevated CRP levels, an indicator of inflammation, independently predict the development of hypertension in older adults. Therefore, it is unclear if younger people have a comparable association. To identify the risk factors for CAD in young people, the Coronary Artery Risk Development in Young People (CARDIA) project was started in 1985-1986. CRP levels over 3 mg/L were linked to a 79% higher incidence of IHT in unadjusted analysis compared to those under 1 mg/L (OR: 1.79, 95%CI: 1.40-2.28)[29].
After adjustment for year 7 BMI (OR: 1.14, 95%CI: 0.86-1.53), as well as for BMI and other potential confounders (OR: 1.13, 95%CI: 0.83-1.52), CRP concentration was not a significant predictor of IHT. Furthermore, no significant association was observed between year 7 CRP levels and longitudinal changes in systolic or DBP after controlling for BMI. These findings were consistent across all racial and sex-specific subgroups. Although CRP appears to be associated with hypertension in younger individuals, this relationship is attenuated after adjustment for BMI, in contrast to observations reported in older populations[29].
Severe and difficult-to-manage hemodynamic instability is commonly associated with systemic conditions such as sepsis and systemic inflammatory response syndrome, both of which are characterized by elevated CRP levels. Ac
Intravenous administration of purified human CRP (3.5 mg CRP/kg body weight) to anesthetized rabbits caused a significant drop in BP while leaving heart rates unaffected. Control animals given bovine serum albumin showed no response. To explore the cellular mechanisms behind this reaction, the study investigated the effect of CRP on cell lines expressing adrenoceptors (CHO-α1A and DU-145). CRP induced dose-dependent Ca2+ signaling. This mobilization was enhanced following maximal adrenoceptor activation by agonists. Researchers hypothesize that CRP prevents adrenoceptor desensitization by interacting with previously uncharacterized surface structures on essential cells[30].
One important hematological measure that reflects systemic inflammation and immunological response is the NLR, which is obtained from a complete blood count[31]. The NLR, which is calculated in complete blood counts by dividing the absolute neutrophil count by the absolute lymphocyte count, has received more attention in recent years. In several clinical diseases, including diabetes, hypertension, metabolic syndrome, obesity, and lifestyle modifications, NLR is a trustworthy biomarker of low-grade inflammation[32,33].
Finding trustworthy prognostic indicators is essential for managing hypertension successfully. One possible inflammatory indicator associated with cardiovascular outcomes is NLR. To examine the relationship between NLR and cardiovascular and all-cause mortality in hypertensive individuals was examined[34]. A significant correlation between NLR and cardiovascular and all-cause mortality was shown using restricted cubic spline analysis. Higher (> 3.5) and lower (≤ 3.5) NLR groups were created by stratifying the participants. A greater NLR was associated with a substantially greater risk of cardiovascular death and all-cause death, according to weighted Cox proportional hazards models[34].
Interestingly, the relationship between NLR and cardiovascular and all-cause mortality was largely mediated by estimated GFR (eGFR) by 5.4% and 4.7%, respectively. Furthermore, the 3-year, 5-year, and 10-year survival areas under the curve (AUC) were 0.68, 0.65, and 0.64, respectively, for all-cause mortality and 0.68, 0.70, and 0.69 for cardiovascular mortality, respectively. In those with hypertension, elevated NLR alone increases the risk of cardiovascular and all-cause death[34].
In recent decades, the NLR has gained considerable attention as a novel inflammatory biomarker. NLR has been widely utilized as a prognostic indicator in malignancies, mortality, and various chronic diseases. Moreover, hy
Hypertension was defined as SBP ≥ 140 mmHg, DBP ≥ 90 mmHg, a prior clinical diagnosis of hypertension, or the use of antihypertensive medication. Accordingly, the association between the NLR and the prevalence of hypertension in the Taiwanese population was evaluated. After adjustment for potential confounders, Cox regression analysis demonstrated that individuals in the highest NLR group had a greater likelihood of being hypertensive[35].
After adjustment for relevant covariates, older individuals in the highest tertile of NLR exhibited a significantly greater likelihood of hypertension compared to those in the lowest tertile. Subgroup analyses stratified by age, BMI, and sex demonstrated a significant association between elevated NLR and hypertension, particularly among males aged over 60 years. In contrast, BMI-stratified groups did not show significant differences following adjustment. Overall, these findings indicate a strong association between NLR and IHT, especially in older adults and male individuals within the Taiwanese population[35].
One of the biggest risk factors for CVD, including ischemic heart disease and stroke (which are consequences of hypertension), is hypertension. Inflammatory indicators such as CRP, interleukins, and tumor necrosis factor-alpha have been linked to a poor outcome in people with hypertension in CVD studies because they impair endothelial function and promote atherosclerosis. The NLR, which is a simple, accessible, and reasonably priced hematological test, has attracted more attention recently[36].
The NLR, reflecting the balance between inflammatory and immune responses, is derived from circulating neutrophil and lymphocyte counts. Neutrophils play a central role in acute inflammation, whereas lymphocytes are critical for the regulation of adaptive immune responses. To date, the NLR has not been extensively evaluated in patients with newly diagnosed hypertension, and its association with hypertension staging remains largely unexplored, representing an area of significant research interest[36].
LV hypertrophy was present in 56% of cases compared with 4% of controls. The case group demonstrated higher mean percentages of neutrophils, lymphocytes, and NLR than the control group. A statistically significant increase in mean NLR was observed with increasing BP in both stage 1 and stage 2 hypertension, with stage 2 hypertension exhibiting significantly higher NLR values than stage 1. NLR was found to be positively and significantly correlated with hypertension severity, indicating that increases in NLR are associated with higher systolic and DBP. Overall, the findings suggest that NLR rises in parallel with the severity of hypertension. This supports a potential role of neutrophils and lymphocytes in inflammatory processes that may contribute to the development and progression of hypertension[36].
Effective strategies for the prevention and management of cardiovascular disease are essential in the context of hypertension. The NLR has been proposed as a potential biomarker of hypertensive disease. Evidence suggests that, compared with controlled hypertension, elevated NLR levels in patients with hypertension are associated with increased mortality risk and resistant hypertension. In a cohort of 42 patients (including 11 with comorbid conditions; 26 females and 16 males), mean NLR values varied across BP categories, with values of 2.06 in elevated BP, 2.87 in stage 1 hypertension, 2.50 in stage 2 hypertension, and 2.20 in hypertensive crisis. Among patients with comorbidities, the mean NLR was higher (4.20; range 0.89-7.52) compared with those with essential hypertension (3.31; range 0.62-6.01). Age-stratified analysis showed mean NLR values of 3.94 in individuals under 40 years, 3.52 in those aged 40-60 years, and 2.24 in those over 60 years. The mean NLR was 2.87 in stage 1 hypertension, with comparatively lower values observed in subsequent stages. Additionally, the mean NLR was 2.97 in patients with hypertension with comorbidities and 4.20 in those with pulmonary pathology. Male patients and individuals under 40 years exhibited higher NLR values than their respective counterparts. Overall, the findings demonstrate significant variation in NLR across age groups, sex, hypertension stages, and the presence of comorbid conditions[37].
Heart structural and functional alterations, such as LV hypertrophy and LV systolic and diastolic dysfunction, are linked to hypertension. A new inflammatory biomarker linked to cardiovascular conditions is the NLR. To assess NLR in children with recently diagnosed essential hypertension, and the connection between cardiac alterations and BP was examined. LV ejection fraction and fractional shortening were used to measure LV systolic function, whereas LV mass index (LVMI) was used to quantify LVH[38].
Doppler and echocardiography were used to measure LV diastolic function using the E/E′ ratio. While there was no change in LV systolic performance between the two groups, the youngsters with hypertension had considerably greater LVMI and E/E′ ratios than the controls. Compared to the control group, the hypertension group had a much greater NLR. Additionally, in the hypertension group, there was a positive correlation between NLR and both SBP and DBP. Additionally, the hypertension group showed a significantly favorable connection between NLR and the E/E′ ratio. NLR did not, however, correlate with LVH or LV systolic function markers in children with hypertension. NLR is strongly correlated with office BP levels and is higher in children with hypertension. Additionally, NLR may be useful in evaluating LV diastolic function in children with hypertension[38].
One significant risk factor for cardiovascular disorders is hypertension. ABP monitoring shows the BP’s diurnal variations and is used to identify and monitor individuals with hypertension. Reduced BP variability is linked to an increased risk of cardiovascular events and hypertensive TOD. Additionally linked to inflammation and elevated cardiovascular risk are the NLR and PLR. To find out how NLR and PLR relate to hypertensive and normotensive patients’ non-dipper status was examined. In comparison to Group 2 (P = 0.001), Group 3 (0.002), and Group 4 (P = 0.023), Group 1’s values were substantially higher. Group 1’s PLR values were substantially greater than Group 2’s in patients with hypertension (P = 0.002)[39].
BP fluctuation between day and night was connected with NLR and PLR, according to Pearson correlation analysis (r = -0.188, P = 0.000 for NLR and r = -0.182, P = 0.000 for PLR). NLR (P = 0.040), PLR (P = 0.021), age (P = 0.006), and hypertension (P = 0.000) were all independent predictors of BP fluctuation, according to regression analysis. In conclusion, NLR and PLR are readily available and reasonably priced indicators of non-dipper status, particularly in hypertensive individuals[39].
It is well established that target organ hypertensive damage and essential hypertension are facilitated by low-grade inflammation. A straightforward and accurate measure of inflammation, the NLR may also help predict hypertension. As NLR quintiles increased, the HRs of hypertension incidence were assessed. The multivariable-adjusted HRs (95%CI) of hypertension were 1.08 (0.92-1.26), 0.97 (0.83-1.14), 1.10 (0.94-1.28), and 1.23 (1.06-1.43), respectively, when compared to individuals with the lowest NLR levels (P for trend < 0.01). Neutrophil and white blood cell counts showed similar outcomes, while lymphocyte numbers did not. Liu et al’s study[40] is the first to demonstrate a substantial correlation between raised NLR levels and a higher risk of hypertension.
In many cardiovascular conditions, a high NLR is a reliable biomarker and independent predictor of persistent vascular inflammation. A comparison of the effects of metoprolol and nebivolol on NLR in individuals with mild to severe hypertension was reported. BMI, BP, blood sugar, total leucocyte count, and lipid profile were also measured both before and after therapy. Both medications considerably reduced baseline BP: Nebivolol 20.5/10.5 and metoprolol 22.5/11.2 (P < 0.001)[41].
Compared to metoprolol, nebivolol decreased total leukocyte count (P = 0.005), neutrophil count (P = 0.003), and lymphocyte count (P = 0.004) in relation to inflammation. Similarly, the NLR ratio was considerably lowered by nebivolol but not by metoprolol (P = 0.07). Compared to metoprolol, nebivolol improved blood sugar and lipid profiles, the differences were not statistically significant. In individuals with hypertension, nebivolol significantly lowers NLR, a measure of subclinical inflammation[41].
Over a billion individuals worldwide suffer from systemic hypertension, the most prevalent cardiovascular illness that kills people by damaging their target organs. A mechanical change in heart function brought on by hypertension may be the cause of LV dysfunction. More significantly, it may be the primary reason for congestive heart failure. Finally, there are two types of LV dysfunction: Systolic and diastolic. Endothelial dysfunction is believed to be linked to LV failure, and a number of substrates, such as the NLR, are surrogate measures of this TOD. The participants’ mean BMI was 29.5 ± 4.9 kg/m2, whereas the control group’s was 27.2 ± 5.0 kg/m2 (P = 0.001). The patients and controls had mean SBP of 149.0 ± 22.5 mmHg and 115.0 ± 11.3 mmHg, respectively (P < 0.001), and mean DBP of 93.0 ± 13.6 mmHg and 70.6 ± 9.1 mmHg, respectively (P < 0.001)[42].
The cases’ mean NLR was 1.35 ± 0.8, whereas the controls’ was 1.23 ± 0.6 (P = 0.272). Those with normal LV function had a considerably lower mean NLR (1.35 ± 0.66 vs 1.43) than those with varying degrees of systolic dysfunction. 2.43 ± 1.11 vs 1.34 ± 0.56 vs ± 0.78 (P = 0.009). As NLR tertiles increased, the fractional wall shortening and LV ejection fraction declined, and the difference between tertiles was statistically significant (P = 0.004 and 0.009). The participants with significant LV systolic dysfunction and those with LV systolic dysfunction had the greatest NLR. Even in the absence of obvious signs of heart failure, NLR is linked to LV systolic dysfunction in hypertensive individuals[42].
One of the main risk factors for atherothrombosis, a serious health issue, is hypertension. The development of atherothrombosis that results in cardiovascular events is mostly influenced by neutrophils and platelets. Currently, two novel systemic inflammation-based indices predictive of cardiovascular risk have been identified: The NLR and the platelet-to-lymphocyte ratio (PLR), both of which are readily computed from a full blood count. The connection between hy
One independent predictor of significant cardiovascular events in hypertension is either concentric or eccentric LV hypertrophy. In cardiovascular illness, a high NLR is linked to poor prognosis and increased mortality. The purpose of this study was to examine the relationships between NLR and various geometric patterns of the LV in individuals with recently diagnosed hypertension. Every group had comparable baseline demographic traits. Compared to the normal geometry and concentric remodeling groups, the eccentric hypertrophy and concentric hypertrophy groups had increased NLR and PLR (P < 0.05, for all)[44].
NLR and LVMI had a strong positive correlation (r = 0.508, P < 0.001). NLR (β = 5.440, P < 0.001), SBP (β = 0.284, P < 0.001), ejection fraction (β = -0.201, P < 0.001), E/A (β = -2.270, P = 0.24), and HDL-C (β = -0.245, P < 0.001) were shown to be independently correlated with LVMI. NLR and PLR were much greater in patients with newly diagnosed hy
The data about variations in the NLR level between patients with dipper and non-dipper hypertension and between patients with and without hypertension were thoroughly examined. NLR levels were significantly higher in the hypertension group than in the control group. Furthermore, the non-dipper group’s NLR levels were greater than those of the dipper group. NLR levels were greater in patients with hypertension than in normotensive individuals[45].
Numerous cardiovascular disorders cause an increase in the NLR. Another study determined if individuals with hypertension and hyperhomocysteinemia (HTH) have elevated NLR. The number of individuals with HTH was up to two times greater in the fourth quartile compared to the first, and there were significant, graded increases in homocysteine (HCY) when participants were categorized based on the NLR quartiles. Participants with hypertension in the HTH group had a substantially greater NLR than those with hypertension in the non-HTH and normotension groups. NLR predicted HTH in an unconditional multiple logistic regression analysis without regard to age, sex, BMI, drinking, smoking, TG, or creatinine (Cr). According to the current investigation, the NLR value rose in the HTH group and had a positive correlation with HCY but not with BP[46].
Over a billion individuals worldwide suffer from hypertension, which is frequently linked to poor outcomes. Since it has been linked to poor outcomes in cardiovascular diseases, the NLR has emerged as a relevant marker. NLR may independently predict outcomes in people with hypertension, and elevated NLR is linked to a higher risk of cardiovascular and all-cause death[47].
One important indicator of cardiovascular events in people with PH is LV hypertrophy. Age, sex, SBP, Cr clearance (Ccr), and NLR were found to be independent risk factors for LVH using multivariate analysis. With 75.3% sensitivity and 59.2% specificity, a combined ROC model exhibited an area under the ROC curve of 0.711 (95%CI: 0.68-0.74). In patients with PH, LVH was independently predicted by age, sex, SBP, SCr, and NLR. The combination diagnostic methodology helps with prompt clinical intervention by offering insightful information for early LVH screening[48].
A new metric for cardiovascular research is the NLR. Higher NLR readings have been linked to poorer clinical outcomes in several cardiovascular conditions, including atherosclerotic heart disease, heart failure, and heart valve disease. The connection between NLR and diastolic dysfunction is unknown, even though NLR has been linked to nearly every cardiovascular condition. Another study assessed the correlation between diastolic dysfunction and NLR. The diastolic dysfunction group had a mean NLR value of 2.07 ± 0.82, whereas the control group had a mean of 1.69 ± 0.60 (P = 0.020). NLR levels were substantially greater in individuals with diastolic dysfunction. Patients with diastolic dysfunction did not vary substantially from controls in any of the other hematologic markers. Compared to those without diastolic dysfunction, patients with diastolic dysfunction exhibited greater NLR levels. Additionally, greater NLR levels were linked to higher degrees of diastolic dysfunction[49].
MAU, or excess urine albumin excretion (UAE) below the proteinuric threshold, has long been identified as a sign of kidney illness and greater cardiovascular risk in both forms of DM. A correlation between MAU and other cardiovascular risk factors, TOD, and the risk of cardiovascular disease in both the general population and certain clinical situations, such as essential hypertension, has been shown by subsequent clinical data. The usefulness of MAU in treating essential hypertension. The reported prevalence of MAU in these participants varies from around 4% to 46% across several studies[50].
These variations may be attributed to the significant intraindividual heterogeneity in UAE, age and ethnicity, variations in assessment methods, and varied definitions of MAU. The majority of research has revealed a direct and ongoing correlation between the UAE and LV mass and BP. On the other hand, it is still unclear if the correlation between the UAE and other variables, including age, sex, smoking, ethnicity, insulin resistance, lipids, and obesity, is caused by confounders, especially BP. The risk of developing cardiovascular disease in the future has been linked to MAU, according to several prospective studies. Notably, in several of these investigations, the incidence of significant cardiovascular events gradually increased with UAE beginning below the traditional MAU criteria[50].
Therefore, MAU may be seen as a marker that combines and reflects the long-term level of activity of multiple other adverse influences on the cardiovascular system, in addition to being a direct risk factor for progressive renal injury. UAE is decreased by antihypertensive therapy, and this impact can be seen within a few days of starting medication. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists appear to be more effective than other antihypertensive medications in lowering UAE. A novel and promising method for managing UAE in patients with hypertension is dual blockage of the RAS using an ACE inhibitor and an angiotensin II receptor antagonist. According to the most recent European hypertension guidelines, determining MAU is advised in the initial work-up of subjects with essential hypertension, despite the possibility that periodic evaluation of this straightforward, low-cost, and predictive marker may be beneficial and economical[50].
UAE can be higher than normal in certain individuals with essential hypertension. Compared to patients with normal UAE, patients with hypertension with MAU have increased BP, especially at night, as well as higher serum levels of uric acid, TG, and cholesterol. By contrast, individuals with MAU had lower levels of HDL-C than those with normal UAE. Compared to individuals with normal UAE, those with MAU showed higher rates of insulin resistance and larger carotid arteries. Following a 7-year follow-up, it found that 54 (21.3%) patients with MAU experienced 12 cardiovascular events, while 87 patients with normal UAE experienced just two (P < 0.0002)[51].
UAE, cholesterol, and DBP were found to be independent predictors of the cardiovascular outcome using stepwise logistic regression analysis. Individuals with MAU had a lower rate of Ccr than individuals with normal UAE. In summary, hypertensive individuals with MAU exhibit a range of biochemical and hormonal abnormalities with pathogenic potential, leading to a higher incidence of cardiovascular events and a higher decline in renal function in patients with hypertension compared to patients with normal UAE[51].
Uncontrolled BP is closely associated with end-organ damage, such as CAD, congestive heart failure, LV hypertrophy, stroke, and peripheral vascular disease. Hypertension is a significant public health concern. As an early indicator of cardiovascular impairment, MAU is prevalent in established hypertension. Early detection of high-risk people using UAE screening allows for prompt actions to lower cardiovascular risk. To find out how often MAU occurs in patients with essential hypertension who are not diabetics, analyze its relationship to LVMI, and look for relationships with the length of hypertension[52].
Thirty-two percent of individuals had MAU, with a frequency of 90.6% among patients with LVH. MAU was substantially correlated with the duration of hypertension. MAU and LV mass were strongly positively correlated. Patients with MAU had substantially higher urinary Cr levels. MAU showed a significant positive connection with the albumin-to- Cr ratio (ACR)[52].
To assess the prevalence of MAU in tertiary care hospital patients with essential hypertension was assessed. MAU in individuals with essential hypertension was quantitatively detected using the Ichroma Fluorescence Immunoassay technique. The age group with the highest prevalence of MAU was 71-80 years old, where all 100 patients had the condition. This was followed by the age groups of 61-70 years old (65.21%), 51-60 years old (12.96%), and 41-50 years old (1.78%). In contrast, no patient in the age group of 31-40 years old had MAU. In conclusion, the incidence of MAU in hypertension increases with age. To treat TOD, it is crucial to assess patients with hypertension, particularly those who are becoming older, for this useful marker[53].
In individuals with DM, albuminuria is linked to a higher risk of cardiovascular disease and damage to target organs. The threshold at which MAU raises risk in nondiabetic patients with hypertension is unknown, although there is evidence that those with MAU levels below the standard suggested screening criteria may be at higher risk for cardiovascular disease. The general and low-risk sample had MAU(C) prevalences of 11% and 9.5%, respectively, whereas MAU(L) prevalences were 11.1% and 10%. Cardiovascular disease was more common in individuals with albuminuria (both MAU[C] and MAU[L]) (24%) than in those without it (14%). The proportion of people with hy
Among individuals with hypertension, MAU is an independent risk factor for catastrophic cardiovascular and cerebrovascular consequences. From January 2013 to January 2014, 100 randomly chosen patients with hypertension participated in an observational study to determine the percentage of MAU and the existence of different TOD in these individuals. Among participants, MAU occurred 36% of the time. Males had a somewhat higher frequency (38.2% vs 33.3%) than females. With the length and intensity of hypertension, the frequency of MAU increased linearly[55].
Smokers were more likely than non-smokers to have it. MAU was linked to diastolic dysfunction (42%) and Grade 2 hypertensive retinopathy (60.7%). Patients who tested positive for MA often had TOD. The percentage of patients with MAU was trending upward as hypertensive participants' ages and length of hypertension experience increased. In individuals with hypertension, hypertensive retinopathy, regional wall motion abnormalities, and neurological deficiency have been identified as sensitive surrogate indicators for MAU[55].
Patients with established essential hypertension often have MAU, which is a predictor of an increased risk of cardiovascular and renal failure. It has been demonstrated that the various cardiovascular risk factors frequently observed in individuals with hypertension are correlated with the existence of MAU. This finding suggests that the greatest indicator of a patient’s elevated worldwide cardiovascular risk may be the identification of higher UAE. A decrease in the amount of albumin in the urine coincides with BP management. Independent of their ability to lower BP, agents that inhibit the RAS have demonstrated the ability to reduce UAE. It is unclear if a reduction in UAE in individuals with hypertension is linked to a better prognosis for their kidneys and heart[56].
In response to volume overload and ventricular wall distension, cardiac tissue produces NPs, including the BNP hormone and the inactive NT-proBNP, which may be increased following myocardial ischemia, hypoxia, and fibrosis[57]. NP production appears to be supported by intricate neurohormonal and inflammatory signaling; endothelin-1 and angiotensin-II are considered powerful regulators[58]. When distended cardiomyocytes experience pressure or volume overload, they release a 32-residue peptide called BNP[59].
One prevalent condition that raises the risk of cardiovascular disease in the future is hypertension. People with hypertension have greater levels of N-terminal BNP; research on its relationship to the risk of hypertension has been conflicting. After an average follow-up of 9.4 years, 466 individuals developed hypertension. There were no variations by sex, BMI, age, or race, and NT-proBNP was not linked to hypertension. Lower-threshold sensitivity analysis yielded similar results. Regarding NT-proBNP, it was not linked to IHT, and this was not different by sex or race[60].
Another study looked into three hypotheses: (1) NT-proBNP is linked to BP variability; (2) NT-proBNP predicts cardiovascular disease events in individuals with hypertension; and (3) NT-proBNP predicts the efficacy of antihypertensive regimens. With a continuous net reclassification improvement of 22.3% (P < 0.0001), the results demonstrated that NT-proBNP enhances cardiovascular disease risk prediction beyond existing predictors[61].
Additionally, a multivariable regression analysis revealed a 2% increase in baseline NT-proBNP for every 1 mmHg rise in the standard deviation (SD) of SBP (P < 0.0001). At 6 months, atenolol-based therapy increased NT-proBNP by 69.6% (P < 0.0001). Amlodipine-based therapy, on the other hand, decreased NT-proBNP by 36.5% (P < 0.0001). After con
The median and range of NT-proBNP for the entire population were 88 (0-2586) pg/mL. The hypertension group had greater NT-proBNP levels than the normotensive group (median 123, range 0-2184 pg/mL vs median 77, range 0-2586 pg/mL; P < 0.01)[62]. NT-proBNP levels were greater in patients with hypertension than in individuals with normal BP in a population study of dyspnea sufferers. When participants with diastolic dysfunction were removed from the study, this difference disappeared. Thus, hypertension may be a confounding factor that reduces the specificity of NT-proBNP levels for heart failure diagnosis. These results should be included in clinical and epidemiological research that involves individuals with both hypertension and heart failure[62].
One of the main risk factors for several heart problems, including hypertensive heart disease, is hypertension. Numerous anatomical and functional alterations in the heart, including LV hypertrophy, diastolic dysfunction, and ultimately systolic failure, can result from this disorder. Early detection and effective therapy are essential for managing hypertensive heart disease to stop the development of congestive heart failure[63].
The NT-proBNP is one possible diagnostic marker that has drawn interest lately. In reaction to elevated wall stress and volume overload, the myocardium secretes NP, such as BNP and its inactive N-terminal fragment. Increased NT-proBNP levels in individuals with hypertensive cardiac disease may be a reflection of the myocardium’s structural and functional alterations brought on by long-term pressure overload. The diagnostic value of NT-proBNP in hypertensive cardiac disease has been the subject of several investigations[63].
The purpose of another study was to examine the plasma levels of circulating cardiac NP, namely B-type or BNP and atrial NP (ANP), in the general population with an emphasis on the relative variations in the severity of human hypertension. Even though ANP and BNP are well-established human BP regulators, nothing is known regarding their association with hypertension at the community level[64].
Compared to normotensive, BNP1-32 and N-terminal proBNP1-76 (NT-proBNP1-76) were significantly decreased in pre-hypertension (P < 0.05), with BNP1-32 significantly decreased in stage 1 as well (P < 0.05). Although proBNP1-108 remained unchanged, the processed form was significantly increased only in stage 2 hypertension (P < 0.05). ANP1-28 remained unchanged, while NT-ANP1-98 was reduced in pre-hypertension (P < 0.05). The authors demonstrated the existence of an impaired production and/or release of proBNP1-108 along with a concomitant reduction of BNP1-32 and NT-proBNP1-76 in the early stages of hypertension, with a significant elevation only in stage 2 hypertension. Importantly, they simultaneously demonstrated a lack of compensatory ANP elevation in advanced hypertension[64].
NPs have a complicated role in hypertension. Therefore, while genetically elevated NP concentrations are linked to a lower risk of hypertension and overweight people who are likely at high risk of hypertension have lower NP concentrations, a higher blood NP concentration is a reliable indicator of pressure-induced cardiac damage in patients with hypertension. To examine the relationships between prevalent and 5-year IHT in a Danish general population sample, serum NT-proBNP, which is a surrogate measure for active BNP, was assessed[65].
One SD increase in baseline log-transformed NT-proBNP concentrations was linked to a 21% higher risk of prevalent hypertension (PHT) (OR: 1.21 [95%CI: 1.13-1.30]; P < 0.001) and a 14% lower risk of IHT (OR: 0.86 [95%CI: 0.76-0.98]; P = 0.020) in models adjusted for age, sex, lifestyle, anthropometric, lipid, metabolic, and renal risk factors, as well as heart rate and baseline BP (only incident model). While lower serum NT-proBNP concentrations are associated with IHT, higher values are associated with PHT. This implies that the pathophysiology of early-stage hypertension may entail reduced circulating BNP, which would lead to decreased vasodilation and natriuresis[65].
One proven predictive factor for cardiovascular diseases is BNP. It is unclear, nonetheless, whether BNP levels and mortality in individuals with acute severe hypertension are related. Another study was to examine the relationship between BNP levels and long-term mortality in patients in the emergency department (ED) with acute severe hypertension[66].
After being admitted to the ED, patients were divided into tertiles based on their BNP values. Within 3 years, 6.4% of the 3099 patients with acute severe hypertension in the first (lowest), 24.8% in the second, and 44.4% in the third (highest) BNP tertile passed away. Patients in the third tertile of BNP and second tertile of BNP had a significantly higher risk of 3-year all-cause mortality than those in the first tertile of BNP after controlling for clinically significant variables[66].
In the general population without heart failure, endothelial dysfunction is linked to cardiovascular mortality; BNP regulates endothelium homeostasis and remodeling. Hsiao et al[67] study looked at the relationship between endothelial dysfunction and serum levels of NT-proBNP in individuals with hypertension. Eight (8.9%) of the hypertensive patients showed poor vascular responsiveness (vascular reactivity index [VRI] < 1.0), 39 (43.3%) showed moderate vascular reactivity (1.0 ≤ VRI < 2.0), and 43 patients showed excellent vascular reactivity.
Poorer vascular reactivity was shown to be linked with older age (P = 0.012) and higher serum NT-pro-BNP levels. VRI values were negatively correlated with older age and log-transformed blood levels of NT-pro-BNP (log-NT-pro-BNP, r =
As a medical and public health concern, hypertension is becoming more and more significant. The Joint National Committee-7 coined the term “pre-hypertension” for those with SBP of 120-139 mmHg and DBP of 80-89 mmHg due to the lifetime risk of hypertension. People who are at risk of developing hypertension frequently have hyperdynamic circulation years before hypertension manifests itself. Because it plays a crucial role in salt and water balance, which in turn affects BP, BNP is a new and potential cardiovascular risk marker[68].
To determine the levels of plasma BNP in individuals with normotension, pre-hypertension, and newly diagnosed hypertension and to track its correlation with rising BP levels, was assessed. According to the Joint National Committee-7, systolic and DBP readings were taken and categorized into three groups based on normotensive to hypertension. BNP was shown to be considerably elevated in the prehypertensive group and to have a positive and statistically significant connection with both systolic and DBP. The study found a favorable correlation between increasing systolic and DBP readings and BNP. Additionally, it was found that BNP was markedly high in the pre-hypertensive stage and may continue to be elevated in persistent hypertension[68].
In a healthy population, even a small rise in plasma N-terminal-pro BNP levels is linked to an increased cardiovascular risk. For hypertension, sacubitril/valsartan has recently been reimbursed in Japan. It is unclear how it affects hypertension’s plasma NT-proBNP levels. Systolic BP tended to drop (P = 0.091) over a pretreatment period, although plasma NT-pro BNP levels were constant (from 204 [132412] pg/mL to 207 [107386] pg/mL, P = 0.84). Systolic pressure and plasma NT-pro BNP levels both dramatically dropped throughout the course of therapy. Plasma NT-pro BNP levels changed much more throughout the on-treatment period than during the pre-treatment period. After 3 months of sacubitril/valsartan medication, there was a substantial drop in plasma NT-proBNP levels[69].
In asymptomatic people without heart failure, elevated NP levels may indicate subclinical cardiac dysfunction and are linked to a higher risk of negative cardiovascular events. Using speckle-tracking-based analyses, another study investigated the relationship between plasma NT-proBNP and both conventional and advanced echocardiographic measures of systolic and diastolic function, including myocardial strain, in a sample of 313 asymptomatic individuals (51% women, mean age 61 years) with hypertension and diastolic dysfunction[70].
Higher NT-proBNP was linked in univariate analyses to higher LV mass index (P = 0.003), left atrial volume index (P = 0.007), lateral E′ velocity (P < 0.0001), E/E′ ratio (P < 0.0001), peak global longitudinal systolic strain (P = 0.015), systolic strain rate (P = 0.021), and early diastolic strain rate (P < 0.0001). NT-proBNP continued to be linked to diastolic dysfunction metrics in multivariable analysis, such as lateral E′ velocity (P = 0.013) and the E/E′ ratio (P = 0.008). Nevertheless, the echocardiographic measure most closely linked to NT-proBNP was early diastolic strain rate. Elevation of NP levels is mostly linked to subclinical diastolic dysfunction in the context of asymptomatic hypertensive heart disease with intact ejection fraction[70].
One known cardiovascular risk factor is the development of structural atherosclerosis, as determined by CIMT[71,72]. A process of endothelium repair is indicated by elevated CIMT. The process of aging causes a decrease in endothelial repair activity but an increase in the necessity for endothelial repair. Since a healthy endothelium is not necessarily indicated by the lack of CIMT growth, there have been no notable correlations found between the annual progression of CIMT and cardiovascular disease[73]. Structural atherosclerosis also requires angiogenesis[74]. By raising peripheral vascular resistance, the suppression of angiogenesis causes hypertension[75].
Angiogenesis, which lowers peripheral BP, may be indicated by the development of structural atherosclerosis. The development of structural atherosclerosis may be advantageous for the prevention of hypertension since angiogenesis lowers peripheral BP. Nonetheless, structural atherosclerosis and hypertension are significantly positively correlated[76].
Consequently, it appears odd that hypertension and structural atherosclerosis are positively correlated. Another significant factor in preventing hypertension is the advancement of structural atherosclerosis, which is strongly correlated with the condition. Over the past 30 years, CIMT has become a significant surrogate measure of TOD in hypertensive heart disease due to its relative simplicity of detection. Nevertheless, depending on how it is used, CIMT’s predictive value in hypertensive heart disease varies. The predictive value of CIMT in patients with hypertensive cardiac disease is described. It gives a summary of CIMT’s shortcomings and potential topics for further study[77].
Probably the most prevalent public health issue in developed nations is hypertension. The high rate of death and morbidity brought on by hypertension has not really decreased despite quick detection and efficient treatment. One of the most significant and deadly consequences of hypertension is vascular wall alterations. By measuring the intima and media layer thickness, ultrasonography was utilized to evaluate this arterial wall disease. One radiologist measured the diameter of the outer vessels and the IMT of the internal and common carotid arteries[78]. The case group’s CAIMT was higher than the controls’ in every carotid artery. Except the right internal carotid (P = 0.024), it was discovered that there was no difference between the duration of having hypertension and the mean CAIMT in the hypertensive. The mean CAIMT of all carotid arteries in hypertension was found to be higher than that of the controls. Furthermore, in hypertensive individuals, the length of the hypertension might hasten the development of atherosclerosis[78].
Another study investigated the relationship between BP levels and atherosclerosis in a rural Chinese community that had a high prevalence of hypertension, a high incidence of stroke, poor income, and little education. Overall, the mean CIMT was 0.57 mm, with 0.56 mm for women and 0.58 mm for males. Increased CIMT was substantially correlated with both hypertension and SBP. For every 1 mmHg rise in SBP, CIMT increase by 0.42 μm (P < 0.001). Participants with a history of hypertension had a mean CIMT that was 17.42 μm higher than those without a history (P < 0.001). As CIMT dropped by 0.44 μm for every 1 mmHg rise in DBP (P = 0.011), DBP was a protective factor[79].
Another study investigated any potential impact modifiers in individuals with hypertension, as well as the relationship between mean CIMT and the risk of first stroke. The risk of first stroke and first ischemic stroke was positively correlated with each SD rise in mean CIMT. Additionally, when CIMT was divided into quartiles, those in quartiles 2 to 4 (≥ 0.66 mm) had greater odds of first stroke (HR: 1.31, 95%CI: 1.06-1.61) and first hemorrhagic stroke (HR: 2.25, 95%CI: 1.11-4.58) than those in quartile 1 (< 0.66 mm). More notably, those with higher mean arterial pressure (≥ 109.3 [quintile 5] against < 109.3 mmHg, P-interaction = 0.024) or DBP levels (≥ 90.7 [quintile 5] vs < 90.7 mmHg, P-interaction = 0.009) showed a substantially larger connection between CIMT and first stroke. In individuals with hypertension, baseline CIMT was significantly positively correlated with the risk of first stroke. Those with higher diastolic or mean arterial pressure levels showed an even greater correlation[80].
According to reports, structural atherosclerosis is favorably correlated with hypertension as measured by CIMT. However, by lowering peripheral vascular resistance, angiogenesis, which is crucial to the development of structural atherosclerosis that prevents hypertension. These correlations raise a paradox: Traits linked to the development of structural atherosclerosis, which is linked to hypertension, may be able to prevent hypertension[81].
Multifaceted investigations are required to elucidate unique processes underlying the connection between structural atherosclerosis and hypertension. Research on circulating cluster of differentiation 34 (CD34)-positive cells, platelets, human T-cell leukemia virus type 1, single-nucleotide polymorphisms (SNPs) of vascular endothelial growth factor, SNPs in BRACA1-associated protein, and SNPs in aldehyde dehydrogenase 2 has demonstrated that active endothelial repair, which causes structural atherosclerosis, helps prevent hypertension. These correlations suggest that structural atherosclerosis development may serve as an indicator of angiogenesis, which lowers peripheral vascular resistance. There has generally been evidence of a positive correlation between structural atherosclerosis and hypertension. On the other hand, structural atherosclerosis advancement may serve as an indicator of exercise that lowers peripheral vascular resistance, hence preventing hypertension[81].
The IMT of the carotid artery is a crucial marker of cardiovascular risk, particularly in individuals with hypertension. Another study focuses on the relationship between IMT and hypertension, the predictive power of IMT for car
Increased CIMT in people without hypertension may be a sign of other, frequently concurrently clustering variables that support the atherosclerotic process. Another study investigated the concept that, in normotensive people, carotid IMT predicts the emergence of new hypertension. The carotid IMT was 0.75 ± 0.16 mm at baseline. Every tertile of the carotid IMT value had a higher incidence of hypertension (39.6, 70.0, and 134.5/1000 person-years in the first, second, and third tertiles, respectively; P < 0.001 by log-rank test). Carotid IMT, as a continuous variable, was found to be a significant predictor of new-onset hypertension using multivariate Cox-hazard analysis after adjustment. Additionally, the carotid IMT at baseline and annual increases in SBP during the follow-up period were significantly correlated. In people with normotension, carotid IMT is an independent predictor of the development of hypertension. Additionally, the results revealed a strong correlation between elevated carotid IMT and BP[83].
One indicator of subclinical atherosclerosis and cardiovascular risk is CIMT. Novel lipid parameters have lately surfaced, and dyslipidemia is a known risk factor for atherosclerosis. To evaluate the relationship between IMT and new lipid markers in individuals with hypertension was examined. A significant correlation was found with TC, LDL-C, non-HDL-C, non-HDL/HDL, LDL/HDL, and TC/HDL. A significant correlation was found between TC, LDL-C, non-HDL-C, non-HDL/HDL, LDL/HDL, and TC/HDL. Several lipid markers are substantially correlated with carotid IMT, with the highest correlation seen for non-HDL/HDL, LDL/HDL, and TC/HDL[84].
Another study was to look at the relationship between BP and carotid plaques and the common CIMT (CCA-IMT). With a multivariate adjusted HR of 1.78 (95%CI: 1.36-2.32) for aberrant CCA-IMT (maximum CCA-IMT > or = 1.0 mm) and 1.45 (95%CI: 1.19-1.77) for carotid plaques, prehypertensives had much higher maximal CCA-IMT values than normotensives. Comparing low prehypertensives to normotensives, the multivariate adjusted OR (aOR) was 1.64 (95%CI: 1.21-2.21) for aberrant CCA-IMT and 1.30 (95%CI: 1.04-1.63) for carotid plaques. After controlling for other cardiovascular risk factors, subjects with hypertension had greater rates of aberrant CCA-IMT and carotid plaques than normotensives. According to the findings, the prevalence of carotid atherosclerosis is much higher in prehypertensive individuals (even those with modest prehypertension) than in normotensive individuals[85].
Stroke is still a major global problem, particularly for those from lower socioeconomic backgrounds. One major cause of stroke that is gaining more and more attention is atherosclerosis. A classic risk factor for atherosclerosis is BP, which includes PP, systolic, and DBP. Its relationship to CIMT has also been extensively researched. The average CIMT was 567.1 μm (583.5 μm for men and 555.7 μm for women)[86].
In the univariate analysis, CIMT was positively linked with SBP, DBP, PP, and mean arterial pressure (MAP); the highest relationships were seen between PP and MAP. Furthermore, PP was shown to be substantially correlated with CIMT in three multiple linear regression models; for every 1 mmHg rise in PP, CIMT increased by at least 0.41 μm (all P < 0.001). It was shown that PP could be the strongest predictor of CIMT when compared to SBP, DBP, and MAP. Therefore, reducing the prevalence of atherosclerosis, particularly in this low socioeconomic class population in China, requires lowering BP, particularly PP levels[86].
A frequent proxy for atherosclerosis is CIMT. Another study investigated the possibility that the observed association between CIMT, BP, and renal function among high-risk families had a genetic foundation because CIMT is linked to hypertension and MAU. A hypertensive parent was used to identify 603 nondiabetic members of 149 Hispanic American households (HA). CIMT, BP, anthropometrics, and renal function—measured by urine microalbumin, blood urea nitrogen (BUN), serum Cr, and Ccr were all part of the phenotyping. The renal function characteristics, BP, BMI, and CIMT all had significant heritabilities. Significant phenotypic correlations were found within family members, with negative correlations between CIMT, BUN, and Cr and positive correlations between CIMT and SBP, urine microalbumin, and Ccr[87].
These correlations persisted after adjusting for BP but not for urine microalbumin. When CIMT was divided into genetic and environmental associations, there were substantial genetic correlations with SBP, urine microalbumin, Ccr, BUN, and Cr, and significant environmental correlations with BUN, Cr, and Ccr. Adjusting for BP did not affect the genetic and environmental relationships; however, adjusting for urine microalbumin eliminated their significance. In these high-risk Hispanic families, SBP, renal function, and CIMT are significantly influenced by genetics. The genetic determinants of subclinical atherosclerosis are similar to those of SBP and, separately, renal function measurements[87].
To quantify the extra impact of hypertension on the IMT in people with type 2 diabetes was investigated. The three groups’ means differed statistically significantly in terms of age, waist circumference, SBP, FPG, glycated hemoglobin (HbA1c), TC, TG, HDL-C, and LDL-C. The three groups’ mean differences in the IMT of the left and right common carotid arteries were statistically significant. In comparison to the healthy control group, the mean carotid artery IMT in the diabetes group and the diabetes + hypertension group appeared to have increased by 24.81% and 31.69%, res
Another study observed the relationship between healthy teenagers’ CIMT and BP. Increased IMT was defined as the top quartile for each sex. After controlling for age, sex, BMI, waist circumference, fasting glucose level, and total/high-density lipoprotein cholesterol ratio, the OR for elevated IMT per 1 SD rise in SBP and DBP was calculated. Increased IMT had an aOR of 1.70 (P = 0.003) for every 12.4 mmHg SBP and 1.25 (P = 0.125) for every 7.0 mmHg DBP. Increased IMT was linked to both SBP (OR: 2.67; P = 0.003) and DBP (OR: 1.68; P = 0.019) in girls when the analyses were done by sex, but not to either DBP (OR: 0.99; P = 0.972) or SBP (OR: 1.46; P = 0.093) in boys. These findings imply that among see
Among the most prevalent causes of arteriosclerotic disorders are DM and hypertension. An increase in CIMT is linked to the existence and severity of CAD, and IMT is often elevated in arterial disorders. Kanwal et al[90] studied to sonographically compare the CIMT in volunteers with hypertension and DM. The control group’s mean CIMT inside the right carotid artery was 0.53 mm, the DM group’s was 0.69 mm, the hypertension group’s was 0.67 mm, and the DM and hypertensive patients’ was 0.98 mm.
The control group’s mean CIMT of the left carotid artery was 0.56 mm, the DM group’s was 0.7 mm, the hypertension group’s was 0.68 mm, and the DM and hypertensive patients’ mean CIMT was 1.01 mm. The mean CIMT of people with DM and those without DM differed significantly. There were notable differences between the DM or hypertension group and the control group. The mean CIMT in the common carotid artery of the control group and those with both DM and hypertension differed more significantly[90].
Lemne et al[91] examined the relationship between atherosclerotic risk factors and IMT and plaque incidence in the carotid arteries of men with borderline hypertension compared to those of normotensive control participants. It assessed the associations between atherosclerotic risk variables, such as age, smoking, lipoprotein levels, and fasting insulin levels, with IMT and plaque incidence. Overall IMT increased somewhat in the borderline hypertensive group (0.73 mm against 0.69 mm; P = 0.07), with the right carotid artery showing the most increase (0.72 mm vs 0.67 mm; P < 0.05). Plaque was more common in borderline hypertensive individuals (26% against 16%, not significant [NS]), and it was more noticeable on the right side (18% vs 6%; P < 0.05). While age was the sole significant predictor of plaque/nonplaque (F = 6.4; P < 0.05), high-density lipoprotein cholesterol and age were consistently associated with IMT (t = 1.94-3.24 and t = -2.25 to -2.69, respectively; P < 0.05).
Furthermore, regardless of group, the IMT of the left and right carotids differed significantly (F = 4.43; P < 0.05). According to the findings, vascular structural alterations take place even in borderline hypertension, however they appear to be more closely linked to general atherosclerotic risk factors than to BP alone. Furthermore, it is hypothesized that the left and right carotid arteries may develop atherosclerotic lesions differently, highlighting the need to measure and report results from both sides when researching CIMT and plaque incidence[91].
Despite being distinct conditions, hypertension and atherosclerosis are connected because hypertension contributes significantly to the development of atherosclerosis. The purpose of this study was to investigate the relationship between LV hypertrophy and CIMT in hypertensive individuals. Age, the length of hypertension, high SBP and DBP, LV hypertrophy, and LV mass index were all statistically significantly correlated with increased CIMT, but not BMI, low-density lipoproteins, or TC[92].
In adults, high BP is a risk factor for atherosclerosis, but it’s unclear if this also applies to children and young adults. This is crucial for directing the treatment of high BP in kids and teenagers. Another study determined if BP and CIMT, a non-invasive indicator of atherosclerosis, are related in children and young adults. Even after controlling for other cardiovascular risk factors, the largest and best-quality studies revealed an independent positive correlation between BP and CIMT in children and young adults. The quality and design of the included studies differed greatly, and a meta-analysis of the data was not feasible[93].
BP and the kidney have a complicated interaction that can negatively impact one another. A slightly lower GFR may be linked to elevated BP. Another study investigated the connection between 24-hour ABP and an accurate measure of GFR in a large cross-sectional study of the general population[94].
GFR was significantly correlated with office DBP, nighttime BP, and daytime BP. GFR was lowered for values > 80 mmHg for DBP throughout the night. The trend for daytime and office DBP was similar, 90 mmHg was the cutoff point for decreased GFR. Office DBP and GFR showed a substantial linear relationship, while ABP and GFR did not. The relationship between GFR and office or ambulatory SBP was neither linear nor non-linear. In the middle-aged healthy general population, a modest decrease in GFR was linked to an increase in diastolic ABP. This might support the idea that essential hypertension has a renal origin, but it could equally be explained by renal damage brought on by high BP[94].
The eGFR may initially decrease when BP is lowered. It found the relationship between eGFR and the early drop in mean arterial pressure. It categorized patients based on their initial eGFR drop and BP target, and after a year, it evaluated the relationship with yearly eGFR decline. The analysis included 41126 eGFR values from 13266 subjects. eGFR was unchanged up to 10 mmHg of BP reduction. The eGFR then decreased linearly by 3.4% (95%CI: 2.9%-3.9%) for every 10 mmHg drop in mean arterial pressure. Based on 95% of the patients, the observed eGFR fall ranged from 26% following a drop in mean arterial pressure of 0 mmHg to 46% following a drop of 40 mmHg[95].
The eGFR slope decreased by 1.24 (95%CI: 1.09-1.39), 1.20 (95%CI: 0.97-1.43), and 1.14 (95%CI: 0.77-1.50) mL/minute per 1.73 m2 per year during intensive treatment and by 0.95 (95%CI: 0.81-1.09), 1.23 (95%CI: 0.97-1.49), and 1.17 (95-1.69) mL/year during standard treatment. It discovered no correlation between baseline eGFR and yearly eGFR reduction with BP-lowering therapy in individuals at high cardiovascular risk with or without DM. An eGFR drop of up to 20% following BP reduction is acceptable and proposes that the limit may be increased to 46% based on the actual BP reduction[95].
Patients with DM who also have hypertension frequently experience impaired GFR. It is a significant contributor to death, morbidity, and low life quality. The frequency and contributing variables of decreased GF in Ethiopian individuals with DM and hypertension are poorly understood. Therefore, Gela et al’s study[96] was to ascertain the incidence of impaired GFR and related variables among hypertensive diabetic patients at referral hospitals in Ethiopia’s Amhara Regional State in 2020.
GFR was estimated using the equations of collaboration with chronic kidney disease (CKD), diet modification in renal disease, and creatinine clearance. The prevalence of an impaired GFR among diabetic individuals with hypertension was 30.1% (95%CI: 25.1%-35.1%), 36.6% (95%CI: 30.1%-40.8%), and 45.4% (95%CI: 39.9%-50.8%). Patients with hypertension and DM had a significant incidence of impaired GFR. Older age, the length of the illness, proteinuria, and elevated blood glucose levels were independent predictors of decreased GFR[96].
In essential hypertension, the impact of GFR and proteinuria on cardiovascular risk. Elevated cardiovascular morbidity and mortality are linked to changes in renal function caused by essential hypertension. Cardiovascular morbidity and death are independently predicted by signs of impaired renal function, such as MAU, elevated blood Cr concentrations, a decline in estimated Cr clearance or GFR, and overt proteinuria. The importance of proteinuria for the community’s cardiovascular prognosis was established by the Framingham Heart Study. Proteinuria’s potential as a risk factor for essential hypertension was evaluated by the INSIGHT Study[97].
In patients with essential hypertension and one or more associated cardiovascular risk factors, the existence of proteinuria at baseline proved to be a highly powerful predictor of the development of cardiovascular events and mortality. According to recent research, the clustering of cardiovascular risk factors seen in metabolic syndrome, which accelerates the development of atherosclerosis, is linked to mild abnormalities of renal function, including proteinuria, both in the general population and in the hypertensive population. Every patient with hypertension has to have their renal function regularly assessed, and even little changes should be taken into account when classifying their cardiovascular risk[97].
It is necessary to look at the connection between hypertension, the use of antihypertensive drugs, and changes in GFR over time in people with maintained GFR. The 2017 American College of Cardiology/American Heart Association Clinical Practice Guideline classified baseline hypertension status (1987-1989) as normal BP, elevated BP, stage 1 hypertension, stage 2 hypertension without medication, or stage 2 hypertension with medication. To assess the relationship between the slope of eGFR and baseline hypertension status, mixed models with random intercepts and random slopes were used. At baseline, stage 1 hypertension, stage 2 hypertension without medication, and stage 2 hypertension with medication were present in 13.2%, 7.3%, and 19.4% of white people and 15.8%, 14.9%, and 39.9% of African Americans[98].
The annual eGFR decline was higher in those with higher BP than in those with normal BP (whites: Elevated BP, -0.11 mL/minute/1.73 m2; stage 1 hypertension, -0.15 mL/minute/1.73 m2; stage 2 hypertension without medication, -0.36 mL/minute/1.73 m2; stage 2 hypertension with medication, -0.16 mL/minute/1.73 m2; African Americans: Elevated BP, -0.21 mL/minute/1.73 m2; stage 2 hypertension, -0.50 mL/minute/1.73 m2; stage 2 hypertension with medication, -0.16 mL/minute/1. For white people, the 30-year predicted probabilities of developing stage G3a+ CKD with normal BP, elevated BP, stage 1 hypertension, stage 2 hypertension without medication, or stage 2 hypertension with medication were 54.4%, 61.6%, 64.7%, 78.1%, and 70.9%, respectively; for African Americans, the corresponding figures were 55.4%, 62.8%, 60.9%, 76.1%, and 66.6%. In a general population cohort, baseline hypertension status was linked to a quicker deterioration in kidney function during a 30-year follow-up than normotension. Among those taking antihypertensive drugs, this disparity was lessened[98].
Examine the relationship between estimated GFR decline (eGFR-d) and concurrently measured vascular risk markers such as office, ambulatory or central BP, pulse pressure, carotid-femoral PWV, CIMT, and renal resistive indexes (RRIs) in patients with type 2 diabetes and diabetic kidney disease (DKD). In addition to the standard clinical workup, vascular risk indicators were evaluated at baseline. The baseline eGFR was 60.2 ± 26.4 mL/minute/1.73 m2, the urine ACR was 49 ± 108 mg/mmoL, and the mean age was 63.8 ± 10.8 years. 43 ± 39 Cr measurements over a period of 7.0 ± 1.9 years were used to calculate mean eGFR-d. From -5.8 ± 2.3 in the first quartile to +1.4 ± 1.7 in the fourth quartile, the average annual eGFR drop was -1.8 ± 3.0 mL/minute/1.73 m2. The average 24-hour systolic and DBP readings were 126 ± 17 mmHg and 74 ± 9 mmHg, respectively. IMT was 0.77 ± 0.21 mm, PWV was 11.8 ± 2.8 m/s, and RRI was 0.76 ± 0.07. DBP was not linked with eGFR-d, whereas SBP and PP were[99].
Compared to office or central SBP, 24-hour SBP was a more reliable indicator of eGFR-d. PWV and RRI showed a correlation with eGFR reduction in univariate regression models, but not in multivariate models that included 24 SBP and ACR. Individuals with DKD and type 2 diabetes showed a highly varied reduction in eGFR. While PWV and RRI did not predict eGFR reduction, 24-hour SBP contributed value to the regular assessment of ACR[99].
When a patient’s estimated GFR is less than 60 mL/minute/1.73 m2, they are diagnosed with CKD. Dialysis and an increased risk of cardiovascular events are associated with low eGFR. Consequently, it’s critical to stop eGFR from declining. Nevertheless, it is still unclear if antihypertensive medication may enhance eGFR in hypertensive individuals with CKD and stop low eGFR from getting even lower. Another examined the impact of antihypertensive medication on eGFR and examined the findings of the Japan Multicenter Investigation for Cardiovascular Disease B (JMIC-B)[100].
After three years of antihypertensive treatment, eGFR in patients with hypertension with CKD (eGFR < 60) increased substantially from 51.87 ± 6.21 (n = 98) to 57.55 ± 19.00 (P < 0.001). The eGFR dramatically dropped from 91.84 ± 23.27 (n = 682) to 88.95 ± 23.67 (P < 0.001) in individuals without CKD (eGFR ≥ 60). eGFR was considerably higher in individuals with CKD and significantly lower in people without CKD, regardless of the kind of antihypertensive medication taken. It demonstrated that in hypertensive individuals with CKD, antihypertensive medication can enhance eGFR[100].
Although the causes of elevated GFR remain unknown, glomerular hyperfiltration predicts the development of nephropathy in hypertension.
Younger age (P < 0.0001), male sex (P < 0.0001), 24-hour SBP (P = 0.0001), body mass (P < 0.0001), white-coat effect (WCE) (P = 0.02), log-epinephrine (P = 0.01), and coffee consumption (P < 0.01) were all significant predictors of GFR in multivariable linear regression[101].
Obesity (OR, 95%CI: 6.1, 3.8-9.8), male sex (2.9, 1.8-4.9), age < 33 years (2.1, 1.5-3.1), ambulatory hypertension (2.0, 1.4-3.0), WCE > 15 mmHg (1.6, 1.1-2.3), heavy coffee consumption (2.0, 1.1-3.8), and epinephrine > 25 μg/24 hours (1.9, 1.2-3.1) were independent predictors of glomerular hyperfiltration in a logistic model. This study’s discovery is that coffee consumption and hyper-reactivity to stress, as measured by urine epinephrine level and WCE, influence glomerular hyperfiltration in the early stages of hypertension[101].
One of the main causes of end-stage renal disease is hypertension, but it’s unclear if high BP also hastens the slow decline in GFR that occurs in the general population as people age. GFR declined at a mean (SD) rate of 0.95 (2.23) mL/minute/year. Between baseline and follow-up, the proportion of people with hypertension (SBP > 140 mmHg, DBP ≥ 90 mmHg, or antihypertensive medication) increased from 42% to 52%[102].
Higher systolic and DBP were linked to slower GFR decrease rates by 0.10 and 0.20 mL/minute/year/10 mmHg, respectively, in multivariable adjusted linear mixed models with time-varying independent variables evaluated at baseline and follow-up (P < 0.05). For the interaction between BP and antihypertensive medication, the link was more pronounced in those using antihypertensive medication than in others. In the general middle-aged population, increased BP is not linked to a faster reduction in GFR during the medium term. Elevated BP is linked to a paradoxically delayed fall in GFR in people on antihypertensive medication[102].
It is unclear if glomerular hyperfiltration and cardiovascular events are related. It examined 8794 people, with an average age of 52 years, who were recruited in 8 prospective trials to determine if glomerular hyperfiltration is independently linked to the probability of a negative outcome. 89% of them had high BP. In comparison to the group with normal eGFR (1.2 per 100 person-year), crude event rates were much higher for both the high (1.8 per 100 person-year) and low (2.1 per 100 person-year) eGFR groups. Both high eGFR (HR: 1.5, 95%CI: 1.2-2.1) and low eGFR [2.0 (1.5-2.6)] participants had a significantly higher risk of cardiovascular events compared to those with normal eGFR in multivariable Cox models that included age, sex, average 24-hour BP, smoking, diabetes, and cholesterol. The multivariable survival model’s hazard estimates remained unchanged when BMI was included. In a sizable multiethnic group of mostly hypertensive people, glomerular hyperfiltration is a robust and independent predictor of cardiovascular events. A U-shaped correlation between negative outcomes and eGFR[103].
The association between renal hyperfiltration (a higher-than-normal estimated GFR, or eGFR) and the incidence risk of hypertension is not well studied. The 10th eGFR deciles (≥ 115.58 mL/minute/1.73 m2) showed a significant correlation with a lower incidence of hypertension in the multivariable Cox regression analysis when compared to the 5th decile (HR: 0.87, 95%CI: 0.85-0.88, P < 0.001). Additionally, relative to normal eGFR levels (90-120 mL/minute/1.73 m2), an eGFR above 120 mL/minute/1.73 m2 was associated with a decreased risk of hypertension. On the other hand, renal hyperfiltration was not linked to a lower risk of hypertension in the subgroup analysis of those over 70. Renal hyperfiltration was linked to a lower incidence of hypertension and this relationship was especially strong in people under 70. Age was probably a factor in the relationship between renal hyperfiltration and a decreased incidence of hypertension[104].
The metabolic syndrome X, a collection of anomalies in glucose and lipid metabolism, is frequently present in individuals with high BP. Another study investigated the hypothesis that those with the metabolic syndrome’s hallmark dyslipidemia, such as high TG and low HDL-C, would have a lower risk of IHD based on their BP. SBP, DBP, fasting cho
Pietri et al[106] investigated the relationship between plasma TG and LV mass in patients with hypertension due to the conflicting findings regarding the prognostic importance of TGs. After adjusting for age, sex, SBP, smoking, and fasting hyperglycemia, TG were linked to LVMI (b = 0.08, P = 0.009). Even after controlling for LDL-C, BMI, and the ApoB/ApoA1 ratio, this link was still significant (b = 0.07, P = 0.04). TGs were associated with LVMI in males (P = 0.001), but not in women (P = NS), according to sex-stratified analysis. Furthermore, TGs increased the likelihood of presenting LVMI exceeding 115 g/m2 by 7% in males with LVH (OR = 1.07 for every 10 mg/dL rise in TGs, P = 0.01). In conclusion, regardless of other risk variables like LDL-C, TGs are linked to LVMI in hypertensive individuals.
Another study characterizing the SBP, DBP, pulse pressure, glucose, creatine, and lipid profile. The prevalence of hypertension and the connection between it and the lipid profile in Uzbekistan were other objectives. Among them, the hypertension group’s TG level was much greater than the normal group’s. The TG and Cr levels were positively correlated with the SBP, whereas the cholesterol level was positively correlated with the pulse pressure. The SBP and TG levels had a positive connection according to a multivariate analysis (adjusted for age and sex). It found a favorable association between the SBP and TG level in the Uzbek population[107].
The greatest significant risk factor for cardiovascular disease globally is hypertension. Due to the ongoing rise in the prevalence of overweight and obesity, obesity-related hypertension has gained significant attention despite the complicated and multifaceted nature of the pathophysiology of hypertension. Obesity-related hypertension has been linked to several processes, such as elevated insulin resistance, changes in adipose-derived cytokines, an increase in sympathetic nervous system activity, and an elevation of the renin-angiotensin-dosterone system. High TG, a prevalent comorbidity in obesity, may be an independent risk factor for new-onset hypertension, according to emerging data from observational studies (including those that use Mendelian randomization). The processes behind TG-associated hypertension, however, are poorly understood. After summarizing the current clinical data that shows TG have a negative impact on BP, over potential underlying mechanisms based on data from studies on humans and animals, with an emphasis on the roles of endothelial function, white blood cells, or lymphocytes, and pulse rate[108]. The findings indicate that elevated BP, advanced organ damage, and a strong correlation with metabolic syndrome were all connected to the coexistence of elevated serum TG and uric acid levels[109].
One of the risk factors for hypercholesterolemia, which causes atherosclerosis, is the Banjar tribe’s tendency to eat meals that are heavy in fat and carbs but low in fiber. BP rises as a result of atherosclerosis’s constriction, hardening, and stiffening. Another study ascertained how TC and TG levels affected the BP of tribal Banjar patients with hypertension at the Cempaka Health Center in Banjarmasin. The Mann-Whitney test yielded P values of 0.389 for SBP and 0.179 for DBP between the groups with normal and high cholesterol. A sphygmomanometer and a stethoscope were used to monitor BP, and there was no discernible difference between the high-cholesterol group and the normal-cholesterol group in terms of systolic and DBP or TG. The Mann-Whitney test yielded P values = 0389 for SBP and P values = 0179 for DBP between the groups with normal and high cholesterol. A sphygmomanometer and a stethoscope were used to monitor BP, and there was no discernible difference between the high-cholesterol group and the normal-cholesterol group in terms of systolic and DBP or TG. The Mann-Whitney test yielded a P value = 0389 for SBP and a P value = 0179 for DBP between the groups with normal BP and high cholesterol. Systolic and DBP did not significantly differ between the normal cholesterol group and the high-cholesterol group; however, TG levels did significantly affect BP[110].
By influencing low-grade systemic inflammation, insulin resistance may have a role in the pathophysiology of hypertension. In contrast to conventional techniques, the TG-glucose (TyG) index has recently been proposed as a trustworthy substitute biochemical indicator of IR. The average TyG index was 8.58 for the hypertension group and 8.39 for the non-hypertension group. After controlling for variables, it was discovered that those with a higher TyG index appeared to have greater risks of hypertension than those with a median value of 8.41. Similarly, this connection was also seen in persons who were female or who were younger than 65. Furthermore, the TyG index and fat may have an additive interaction on hypertension[111].
High rates of morbidity and death are linked to hypertension. BP monitoring at home or in the clinic is primarily responsible for the treatment’s effectiveness in patients with hypertension. The ratio of HDL-C to TG (THR) is a metabolic and inflammatory indicator. Compared to the well-managed hypertension group (3.07 [0.71%-35.8%]), the THR of the poorly controlled hypertension group (3.9 [1.91%-88.7%]) was substantially greater. THR greater than 3.26% had a sensitivity of 72% and a specificity of 52% for predicting poor BP management (AUC: 0.64, P < 0.01, 95%CI: 59%-70%). Since high THR levels may indicate poor BP regulation in population, patients with hypertension may benefit from tighter BP monitoring[112].
A few prospective studies have identified dyslipidemia as a risk factor for IHT; however, no study has specifically evaluated various lipid measures, such as the lipid ratios, such as TG/HDL-C and TC/HDL-C, as predictors of hypertension among Middle Eastern women with high prevalences of both dyslipidemia and hypertension. In conclusion, even in women without diabetes and central or general obesity, dyslipidemia—specifically, serum TG and TG/HDL-C—may help identify women at risk for hypertension[113].
One of the main risk factors for the burden of disease worldwide, especially in industrialized nations, is a high BMI. Interventions centered on obesity and metabolic syndrome are necessary because BMI interacts with metabolic risk factors, such as high BP, high blood glucose, poor physical activity, and the use of sugar-sweetened drinks[114].
Using an unselected sample of adults evaluated during the longevity check-up 7+ (lookup 7+) research, the current study was conducted to offer a better understanding of the association between various levels of BMI and increasing risk for hypertension. Based on the World Health Organisation’s suggested BMI cutoffs, 2896 individuals (38%) were overweight, and 1135 participants (15%) were obese, with 893 participants (11.8%) in class I, 186 participants (2.5%) in class II, and 56 people (0.7%) in class III. The prevalence of hypertension was 45% among those with a normal BMI, 67% among those who were overweight, 79% among those in obesity classes I and II, and up to 87% among those in obesity class III (P for trend < 0.001). Significantly varied systolic and DBP distributions across BMI levels were persistent after controlling for age. Overall, across all BMI levels, the average systolic and DBP increased noticeably and linearly. In summary, it discovered a gradient of rising BP associated with greater BMI levels. The presence of this gradient even in the fully adjusted studies implies that, irrespective of other clinical risk factors, BMI may directly affect BP[115].
Diabetes mellitus and hypertension are strongly associated with BMI. However, it is still unclear how BMI and hypertension-diabetes comorbidity are related in China’s senior population. DM and hypertension were the secondary outcomes. Chinese recommendations classified BMI into four groups: Underweight (less than 18.5 kg/m2), normal weight (between 18.5 kg/m2 and 23.9 kg/m2), overweight (between 24.0 kg/m2 and 27.9 kg/m2), and obesity (more than 28.0 kg/m2). 5,342 people with hypertension, 6335 with diabetes, and 6414 with hypertension-diabetes comorbidity (all people 65 years of age and above) were included. When compared to the normal weight group (reference), the adjusted HR for the underweight group was 0.747 (95%CI: 0.651-0.857), for the overweight group it was 1.517 (95%CI: 1.309-1.758), and for the obesity group it was 1.620 (95%CI: 1.237-2.121). The adjusted HR was 1.043 (95%CI: 1.029-1.059) when taking BMI into account as a continuous variable. The HR for people with BMI > 24.0 (as opposed to BMI < 24.0) was 1.486 (95%CI: 1.301-1.698) using a multi-model adjustment technique based on the directed acyclic graph[116].
The probability of hypertension-diabetes comorbidity is positively correlated with BMI (range in BMI > 24), according to restricted cubic splines. Similar findings to the primary outcome were found in the association between BMI and secondary outcomes. Additionally, with an adjusted HR of 0.334 (95%CI: 0.235-0.475), other ethnic groups had a considerably lower risk of the main outcome than the Han ethnic group. For the secondary outcomes, similar results were seen. In China’s senior population, a greater BMI is substantially linked to an increased risk of hypertension, diabetes, and hypertension-diabetes comorbidity. Furthermore, Han individuals are significantly more likely than non-Han individuals to have hypertension, diabetes, and hypertension-diabetes comorbidity[116].
The connections between BMI and several chronic illnesses, including asthma and hypertension, have been extensively documented. However, there is still a lack of studies aimed at comprehending the health effects of medical school on students, who face significant academic pressure. Furthermore, 18.1%, 2.7%, and 13.5% of people had prehypertension, hypertension, and inadequate vital capacity index (VCI), respectively. Interestingly, compared to their female peers, male students had a greater frequency of the previously described health problems[117].
SBP, DBP, and VC showed positive correlations with BMI. BMI and VCI, however, showed a negative connection. Subsequent analysis showed that compared to their normal-weight peers, overweight and obese people had a higher risk of high BP [(OR: 2.05, 95%CI: 1.15-3.67) and (OR: 5.44, 95%CI: 2.28-13.02), respectively]. Additionally, underweight participants had a lower risk of poor VCI (OR: 0.19, 95%CI: 0.07-0.52), whereas these groups had a greater risk [(OR: 5.25, 95%CI: 3.04-9.06) and (OR: 15.61, 95%CI: 6.81-35.81), respectively]. BMI showed a significant negative link with VCI and a substantial positive correlation with both VC and BP[117].
Even though both obesity and hypertension are becoming more common in the United States, the relationship between the two conditions throughout life has not been well studied. In 1132 white men from The Johns Hopkins Precursors research, a prospective cohort research, it examined the relationship between BMI in early adulthood, middle age, and later life with the risk of developing hypertension. Young adults who were obese (BMI ≥ 30 kg/m2) had a significant correlation with IHT (HR: 4.17; 95%CI: 2.34-7.42). A higher risk was also indicated by being overweight (BMI 25 to < 30 kg/m2) (HR: 1.58; 95%CI: 1.28-1.96). In comparison to men of normal weight at age 25, men who became overweight or obese at age 45 were at higher risk (HR: 0.91; 95%CI: 0.43-1.92), but not men who were overweight or obese at age 25 and went back to normal weight at age 45[118].
The rate of change in BMI over the life course increased the risk of IHT in a dose-response manner, with the highest risk among men with the greatest increase in BMI, after controlling for time-dependent number of cigarettes smoked, cups of coffee consumed, alcohol intake, physical activity, parental premature hypertension, and baseline BMI. From young adulthood through middle age and into late life, the results highlight the significance of increased weight and weight growth in raising the risk of hypertension[118].
It has been shown that populations with high BMI have higher BP. Heart disease is more common in those who are overweight and have high BP. To assess the relationship between BP and BMI in patients with hypertension, both male and female, who were at least 18 years old, was reported. They had a mean SBP of 141.78 ± 13.00 mmHg, a DBP of 85.21 ± 10.03 mmHg, and a mean BMI of 26.83 ± 5.83 kg/m2. The findings also revealed a significant negative association between the BMI and the SBP level (ρ = -0.212, P = 0.011) and DBP level (ρ = -0.208, P = 0.013) in men, but not in females. There was no significant association between the patients’ BMI and their systolic or DBP levels in females, while there was a substantially weak negative correlation in men[119].
The main risk factors for several serious illnesses include obesity and high BP. The purpose of another study was to investigate the relationship between teenage BP and BMI, a validated measure of obesity. Both male and female patients showed a significant positive connection between BMI and SBP and DBP. Only overweight males showed a significant association with overweight females, according to further analysis based on BMI subgroups. BMI and BP are linearly correlated. Variations in autonomic function and metabolism might be the cause of the observed disparities between the BMI subgroups[120].
Nutrition, drinking, and food consumption are all related to obesity. Examining the relationship between body weight fluctuations, BMI, and the prevalence of hypertension is essential, with a particular emphasis on any sex disparities. With an OR of 1.11 (95%CI: 1.11-1.12) for both sexes, a greater BMI was associated with a higher risk of hypertension. Gaining weight was linked to the development of hypertension, with an OR (95%CI) of 1.08 (1.07-1.08) for women and 1.09 (1.09-1.10) for males. Even among those who were not obese, this connection persisted across all BMI levels, with the impact being more pronounced in men. In the healthy Japanese population, weight fluctuation and BMI both have a role in the development of hypertension, with variations depending on sex. Weight reduction may lower the risk of hypertension for persons with and without obesity, highlighting the need for weight stability through diet and nutrition control, particularly for women[121].
The risk of hypertension increases with a high BMI. The dose-dependent relationship between BMI and hypertension, however, is not well understood. Thus, it examined the dose-response connection between BMI and hypertension risk and examined the prevalence of hypertension in 7568 participants from Jiangsu Province, Eastern China. Systolic and DBP were substantially correlated with BMI. For every 1 kg/m2 rise in BMI, the fully-aOR with a 95%CI for hypertension was 1.17 (1.15-1.19)[122].
Additionally, after controlling for confounders, the OR (95%CI) for hypertension in the group with the highest BMI (obesity) was 4.14 (3.45-4.96) in comparison to the normal group. It revealed a positive and linear dose-response connection between BMI and the risk of hypertension. A significant and linear dose-response connection between BMI and the risk of hypertension was shown. The findings of the investigation support therapeutic measures linked to BMI that lower the incidence of hypertension[122].
Although the prevalence of obesity and hypertension is rising in developing nations, little is known about how BMI affects BP in these groups. Another study looked at the relationship between BMI and BP in three Asian and African groups. While low BMI was common in Ethiopia and Vietnam, ranging from 33% to 43%, overweight/obesity was found to be very frequent among Indonesian women (25%) and men (10%). Men’s mean SBP ranged from 117.15 (15.35) in Ethiopia to 127.33 (17.80) in Indonesia. In Indonesia, the greatest rates of hypertension were found in women (25%) and males (24%). As BMI grew, mean BP levels rose[123].
The OR (95%CI) was 2.47 (1.42-4.29) in Ethiopia, 2.67 (1.75-4.08) in Vietnam, and 7.64 (3.88-15.0) in Indonesia for population groups that were overweight or obese. In all three groups, there was a substantial and positive association between BMI and both SBP and DBP; the correlation coefficient (r) ranged from 0.23 to 0.27, P < 0.01. In communities at the beginning of the epidemiologic shift, high BP is associated with undernutrition[123].
The absolute risk of illness for the rest of a person’s life is indicated by lifetime risk (LTR). Since no prior research has evaluated this risk, authors sought to determine the LTRs for coronary heart disease (CHD) mortality linked to BP and TC levels in an Asian population by a meta-analysis of individual participant data. At the index age of 35, the equivalent LTR was > 1.84%, whereas the 10-year risk of CHD death was < 0.11%[124].
Participants with high TC levels [≥ 5.7 mmol/L (220 mg/dL)] showed a sharp rise in the LTR of CHD at index age 35 years. In men and women with grade 2-3 hypertension and elevated TC, this risk was 7.73%/5.77% (95%CI: 3.53%-10.28%/3.83%-7.25%). The absolute differences in LTRs between the low and high TC groups in the normal and high BP groups were < 0.25% for males and ≤ 0.40% for women[124].
Chen et al[125] study examined the associations between TC, brachial-ankle PWV (BaPWV), and SBP and quantified their individual impacts using 45092 participants from the Kailuan study. According to multivariate linear regression analysis, SBP increased by 0.33 mmHg and 0.044 mmHg for every SD rise in TC and BaPWV, respectively; BaPWV increased by 5.34 cm/s for every SD increase in TC. Arterial stiffness mediated the TC-induced SBP increase in almost half of the population, according to mediation analysis (indirect effect, 0.73; percent mediated, 54.5%).
Additionally, in fewer than half of the males (indirect effect, 0.70; percent mediated, 47.9%), arterial stiffness mediated the TC-induced SBP rise; however, the results were not statistically significant in females. In summary, there is a positive correlation between TC and BaPWV and SBP, but not between TC and BaPWV. Arterial stiffness mediates about half of the increase in SBP that causes TC[125].
Because it raises the risk of cardiovascular disease, brain damage, kidney damage, and other conditions, hypertension is one of the disorders that causes problems worldwide. However, because there are frequently no symptoms, this is sometimes overlooked. Both the development of hypertension and BP management are influenced by lifestyle. Cholesterol is a contributing factor to hypertension. BP rises as a result of blood vessel blockage and stiffness brought on by cholesterol accumulation. Eight evaluations of the literature revealed that most individuals with high cholesterol would also have higher BP. Following this investigation, a correlation was shown between hypertension and cholesterol levels[126].
Coronary heart disease risk is doubled by hypertension. The risk of CHD is only 25% lower when hypertension is treated. In hypertensive individuals, treating hypercholesterolemia lowers residual CHD risk by more than 35%. The National Health and Nutrition Examination Surveys from 1988 to 1994, 1999 to 2004, and 2005 to 2010 were examined to evaluate advancements in the management of concomitant hypertension and hypercholesterolemia. 60.7% to 64.3% of hypertensives were hypercholesterolemic across surveys. Concomitant hypertension and LDL-C [5.0% (95%CI: 3.3%-6.7%) to 30.7% (95%CI, 27.9%-33.4%)], control of LDL-C9.2% (95%CI: 6.6%-11.9%) to 45.4% (95%CI: 42.6%-48.3%)], and non-high-density lipoprotein cholesterol [1.8% (95%CI: 0.4%-3.2%) to 26.9% (95%CI: 24.4%-29.5%)]. According to multivariable logistic regression, statin [10.7 (8.1-14.3)] and antihypertensive [3.32 (2.45-4.50)] medications, age [0.77 (0.69-0.88)/10-year increase], ≥ 2 healthcare visits/year [1.90 (1.26-2.87)], black race [0.59 (0.44-0.80)], Hispanic ethnicity [0.62 (0.43-0.56)], DM [0.54 (0.44-0.56)][127].
Two prevalent comorbidities in the elderly that significantly raise the risk of cardiovascular disease are hypertension and hypercholesterolemia. Although there is no local evidence on the direct association between the two in the older population, the two are frequently seen together. Thirteen (81.25%) of the sixteen responders had BP within the hypertension range, and thirteen (81.25%) had TC values more than 200 mg/dL. The statistical test revealed a strong correlation between BP and cholesterol levels, with a value of P = 0.018 (P < 0.05). BP and cholesterol levels in the elderly were significantly correlated[128].
One major risk factor for cardiovascular disease is hypertension. Finding novel hypertension risk factors is essential[129]. The purpose of another study is to ascertain the predictive significance of HbA1c and FPG in the development of hypertension. Another study looked at 16026 people who had yearly screenings at the People’s Hospital of Yuxi in Yunnan, China, between 2013 and 2016, who did not have diabetes or other cardiovascular risk factors. Based on their FPG and HbA1c readings, the subjects were further separated into four subgroups: Normoglycemia, impaired HbA1c alone, FPG only, and both parameters impaired[129].
According to the study, prediabetes was independently linked to a higher risk of hypertension. Regardless of the group, the examination of various HbA1c and FPG subgroups revealed that FPG was a stronger predictor of hy
To investigate the treatment results of FPG in patients with diabetes with or without hypertension and BP in patients with hypertension with or without diabetes. Patients with hypertension alone showed a substantial decrease in both SBP and DBP (Coef. = -0.00088, P < 0.001; Coef. = -0.00081, P < 0.001). DBP significantly dropped in comorbid individuals (Coef. = -0.00033, P < 0.001)[130].
Comorbid patients’ PP increased significantly (Coef. = 0.00044, P < 0.001). Only in individuals with hypertension did the BP control rate considerably rise (OR = 1.00039, P < 0.001). In patients with diabetes with or without hypertension, FPG control rates significantly increased (OR = 1.00013, P < 0.001; OR = 1.00020, P < 0.001). Compared to patients with hypertension alone, comorbid patients had lower baseline SBP and DBP but higher latest SBP (Coef. = -1.18872, P < 0.001; Coef. = -1.16049, P < 0.001; Coef. = 1.0634, P < 0.001). Compared to patients with either disease alone, comorbid patients had poorer baseline BP and FPG control rates, and the differences were more pronounced at the most recent follow-up (OR = 0.28086, P < 0.001; OR = 0.91012, P = 0.049; OR = 0.04020, P < 0.001; OR = 0.69465, P < 0.001). The management results for FPG and BP have improved[130].
Diabetes mellitus and hypertension have grown to be significant public health concerns, and prior research has demonstrated a link between the two conditions. Nevertheless, specific details regarding this relationship are lacking. The purpose of the study was to investigate the relationships between various BP and fasting blood glucose levels. Sex differences were seen in the distributions of DBP (χ2 = 460.20, P < 0.001) and SBP (χ2 = 710.76, P < 0.001). FBG was favorably correlated with SBP (P30 to P90) and DBP (P20 to P90) in men, according to quantile regression, whereas Lambda-mu-sigma demonstrated that the relationships between BP and FBG got stronger when the FBG levels were around 5.6 mmol/L. FBG was favorably correlated with SBP in females from just P85 to P90. In conclusion, FBG has a sex-dependent positive association with BP[131].
Examining the relationship between fasting blood glucose and new-onset hypertension, as well as any potential synergistic effects of modifying numerous risk variables, was reported. Higher baseline fasting blood glucose levels significantly increased the risk of new-onset hypertension in women, in contrast to lower baseline fasting blood glucose levels. Furthermore, women with greater TC had a significantly larger correlation with the probability of developing new-onset hypertension. Nevertheless, there was no correlation discovered between the risk of new-onset hypertension in males and fasting blood glucose[132].
Blood glucose levels that are higher than usual but below the diagnostic threshold for DM are referred to as pre DM. Another study sought to ascertain the significance of BP and the ankle-brachial index (ABI) between two patient groups as well as the relationship between fasting blood glucose levels and interarm BP difference (IAD), interleg BP difference (ILD), four-limb BP, and ABI. SBP and PP were considerably greater in the impaired fasting glucose (IFG) group compared to the normal fasting glucose (NFG) group[133].
FBG levels and SBP showed a strong positive correlation. The ABI of the IFG group was lower than that of the NFG group. In contrast, there was no discernible difference between the two groups’ IAD and ILD. Additionally, a high frequency of prediabetes was substantially linked with dyslipidemia, metabolic syndrome, and hypertension. Those with normoglycemia had lower BP than those with prediabetes. Hypertension, MetS, and dyslipidemia were linked to prediabetes[133].
Lou et al[134], evaluated the relationship between IHT and the FPG change trajectory in the Chinese population. The probability of hypertension rose with increasing FPG change trajectories (aOR: 1.22, 95%CI: 1.07-1.40), bell-shape trajectories (aOR: 1.15, 95%CI: 1.02-1.30), and other-shape trajectories (aOR: 1.13, 95%CI: 1.02-1.25), which demonstrated greater variability of FPG when baseline potential confounders were present. Furthermore, independent of age or BMI, the growing FPG change trajectory was linked to a greater likelihood of hypertension than the decreasing group; however, this association was only significant in men and those with baseline normal FPG. The largest risk of hypertension is determined by the growing FPG change trajectory, highlighting the need to maintain low and stable FPG levels, particularly in males and those with normal FPG.
A common glycemic disease that often develops into DM is IFG. It has never been thoroughly studied how IFG, BP, and other risk variables relate to death. Males with IFG had substantially higher mean BMI, serum TG and cholesterol levels, systolic, diastolic, and pulse BP than males with NFG (FPG 3.9 mmol/L to 6.0 mmol/L). SBP level affected the relative risk of 8-year cardiovascular mortality linked to IFG after controlling for confounding factors [1.02 (95%CI: 0.62-1.70) when < 140 mmHg and 2.10 (95%CI: 1.16-3.80) between 140 mmHg and 160 mmHg][135].
On the other hand, the glycemic status had a significant impact on the relative risk of 8-year cardiovascular death linked to moderate systolic hypertension (140 mmHg to 159 mmHg) as opposed to normal SBP (< 140 mmHg) 2.97 (95%CI: 1.58-5.55) for men with IFG compared with 1.35 (95%CI: 0.84-2.18) for those with NFG. In conclusion, individuals with IFG who are at risk of cardiovascular and overall mortality can be identified by the presence of mild systolic hypertension, and vice versa, most likely through the metabolic syndrome[135].
There is evidence that abnormal fasting blood glucose, hypertension, and benign prostatic hyperplasia may be related. Another study looked at whether hypertension in elderly individuals with benign prostatic hyperplasia is correlated with abnormal fasting blood glucose. The findings showed that there was no correlation between a higher risk of hypertension and either IFG or high risk of type 2 DM. Similar results were found when patients were classified according to the severity of their hypertension. The nonsignificant trends for high risk of type 2 DM and IFG/high risk of type 2 DM to be associated with hypertension remained after controlling for confounding variables. In contrast to previous research, this study indicates that in older individuals with benign prostatic hyperplasia, there may not be a significant correlation between fasting blood glucose levels and hypertension[136].
Pre-diabetes is a known risk factor for developing overt DM, which is linked to the onset of hypertension and vice versa. It is unclear, therefore, how pre-diabetes and HbA1c in particular function as separate risk factors for the development of hypertension. In a sizable cohort of normotensive individuals, another study sought to assess the relationship between the development of hypertension and FPG and HbA1c levels in the pre-diabetes range. The prediabetic group had a 2.89-fold (95%CI: 2.19-3.83; P < 0.0001) higher risk for hypertension, according to a cumulative hazard function for the development of hypertension. Pre-diabetes was shown to be independently linked to a 1.95-fold (95%CI: 1.43-2.52; P < 0.0001) higher risk for hypertension in a multivariable Cox proportional hazard regression model adjusted to common confounding risk variables for hypertension[137].
While IFG only demonstrated a 2.13-fold (95%CI: 1.46-3.11; P < 0.0001) higher risk for hypertension compared to normoglycemic, and a 2.55-fold (95%CI: 1.85-3.51; P < 0.0001) greater risk for hypertension when both parameters were impaired, impaired HbA1C alone was not observed to be independently related with hypertension. Future development of hypertension is independently linked to FPG in the pre-diabetes range, but not HbA1c. Thus, results emphasize the critical predictive function of IFG and the restricted significance of HbA1c for the development of hypertension[137].
Early adulthood FBG was greater in those with childhood hypertension (mean difference 8.96 mg/dL), and the risk of high FBG (≥ 126 mg/dL) was 4.16 times higher. Individuals who were overweight, had low DBP, had a faster pulse rate, or were African Americans were more affected. Elevated FBG in early adulthood is associated with childhood hy
The purpose of another study was to look at the prevalence of hypertension and how it related to fasting blood glucose levels in Korea. High TG (aHR: 1.292; 95%CI: 1.280-1.303), a history of dyslipidemia (aHR: 1.279; 95%CI: 1.253-1.305), prediabetes (aHR: 1.249; 95%CI: 1.237-1.260), high fasting blood glucose (aHR: 1.836; 95%CI: 1.810-1.862). High blood glucose was found to be an independent risk factor for developing hypertension in real-world Korean data[139].
To evaluate long-term changes in FPG and BP in primary care patients with type 2 DM and concurrent hypertension, and to investigate variables linked to patients’ failure to improve FPG and BP during follow-up. Over one-fourth (27.2% [1467/5398]) of patients did not have any improvement in either BP or FPG during follow-up. Out of every patient, significant increases in FPG (0.12 mmol/L, 0.09 to 0.15; P < 0.001), DBP (0.73 mmHg, 0.54 to 0.92; P < 0.001), and SBP (2.31 mmHg, 95%CI: 2.04 to 2.59; P < 0.001) at follow-up. No improvement in BP and FPG at follow-up was linked to changes in BMI (aOR = 1.045, 1.003 to 1.089; P = 0.037), poor adherence to lifestyle advice (aOR = 1.548, 1.356 to 1.766; P < 0.001), and unwillingness to actively enroll in health-care plans run by the family doctor team (aOR = 1.379, 1.128 to 1.685; P = 0.001)[140]. In an urban Northern Chinese population, elevated FPG and 2hPG levels are independent risk factors for hypertension development, but not HbA1c levels[141]. To investigate whether the occurrence of hypertension in nondiabetic and nonhypertensive first-degree relatives of individuals with type 2 diabetes is correlated with plasma glucose (PG) levels. Regardless of age, sex, obesity, high cholesterol, HDL-C, LDL-C, TG, education, and SBP, the PG levels at baseline were linked to the occurrence of hypertension. Compared to those with normal glucose tolerance, those with impaired glucose tolerance had a 54% higher risk of developing hypertension (HR: 1.54; 95%CI: 1.33-1.77). Additionally, the risk of developing hypertension was 23% (HR: 1.23; 95%CI: 1.01-1.50) higher in those with IFG. Incident hypertension was regularly linked to high PG levels[142].
Optimal management of BP and blood glucose is linked to fewer occurrences of cardiovascular disease. Diabetes and hypertension are significant risk factors for cardiovascular illnesses. Therefore, the purpose of this study was to determine the prevalence and related determinants of regulated BP and blood glucose levels in individuals with both type 2 DM and hypertension. Of the 329 individuals with both hypertension and type 2 diabetes, 41.3% (95%CI: 36.1%-46.8%) had managed BP, 57.1% (95%CI: 51.7%-62.4%) had controlled blood glucose, and 21.8% (95%CI: 17.7%-26.7%) had both. Controlled BP was strongly correlated with advanced age, non-formal education, single-dose anti-hypertensives or anti-diabetic drugs, employment, hyperlipidemia, or stroke co-morbidities[143].
Additionally, the most practical method of screening for glucose problems was evaluated. Of the participants, 66 (6%) had type 2 diabetes, 220 (20%) had impaired glucose tolerance, and 167 (15%) had IFG. It would have overlooked around 40% of patients with impaired glucose tolerance if it had only performed an oral glucose tolerance test on hypertensive participants whose FPG was ≥ 5.6 mmol/L. 88% of all cases of impaired glucose tolerance and 96% of all cases of type 2 diabetes were recognized using the International Diabetes Federation’s metabolic syndrome criteria. The incidence of central obesity was concerning: 82% of men and 90% of women had waist circumferences of at least 94 cm and 80 cm, respectively. Central obesity and impaired glucose homeostasis are prevalent in hypertensive individuals. It seems sensible to do an oral glucose tolerance test, at least for hypertensive individuals with metabolic syndrome. A key objective in the treatment of patients with hypertension is weight stability[144].
One known prognostic indicator for PAH is elevated RAP. Disturbances in right atrial (RA) function in PAH, however, are poorly understood. In the Imatinib in Pulmonary Arterial Hypertension, a Randomized Efficacy Study trial, 65 patients with PAH, 6-minute walk distance ≤ 450 m, and pulmonary vascular resistance > 800 dynes·s/cm5, despite therapy with at least two PAH-specific medications, had their reservoir (RA longitudinal strain [RA LS]), conduit (RA early LS rate), and active (RA late LS rate)[145].
It investigated the relationship between invasive pulmonary hemodynamics, cardiac structure and function, and NT-proBNP and RA functional parameters. Even after controlling for RA area and invasive RA pressure, patients with PAH had lower RA LS and early LS rates (27.1 ± 11.6 vs 56.9 ± 12.7, adjusted P < 0.001 and -0.6 ± 0.5 vs -1.5 ± 0.5, adjusted P < 0.001, respectively); however, RA late LS rates were comparable between groups (-1.4 ± 0.7 vs -1.5 ± 0.4; P = 0.42). Greater RA size (r = -0.50; P < 0.0001) and pressure (r = -0.37; P = 0.002) were associated with poorer RA LS in patients with PAH, but not pulmonary artery pressure (r = -0.07; P = 0.58). Independent of RA size and pressure, worse RA LS was also linked to increased NT-proBNP and RV hypertrophy and dysfunction. Regardless of RA size or pressure, PAH impairs RA reservoir and passive conduit functions, which probably indicate RV failure and overload[145].
In patients with acquired heart disease-related heart failure, RAP, a composite measure of RV diastolic function, volume status, and right heart compliance, is a predictor of death. It postulated that RAP would be linked to the severity of the illness and cardiovascular adverse events in patients with tetralogy of Fallot (TOF), as these individuals may have aberrant RA and ventricular mechanics due to myocardial damage and remodeling. To ascertain the relationship between RAP and many TOF disease severity categories (% of anticipated peak oxygen consumption, atrial or ventricular arrhythmia, and hospitalization for heart failure), as well as cardiovascular adverse effects, which include heart transplantation, prolonged ventricular tachycardia, resuscitated or aborted sudden death, and death, were reported. The median RAP was 10 mmHg (interquartile range: 7-13 mmHg), and the mean was 10.7 ± 5.2 mmHg among 225 individuals. Increasing RAP was linked to decreased exercise capacity (peak oxygen consumption; R2 = 0.74, r = -0.86; P < 0.001), atrial or ventricular arrhythmias (OR: 5.01, 95%CI: 1.22-23.49; P < 0.001), and heart failure hospitalization (OR: 1.47, 95%CI: 1.10-2.39; P = 0.033) per 5 mmHg. Cardiovascular adverse events were predicted by RAP per 5 mmHg (HR: 1.28, 95%CI: 1.10-1.47; P = 0.028)[146].
Two-dimensional and Doppler echocardiography were used to assess the impact of oral antihypertensive medications on RA function over 16 weeks in 64 individuals with mild-to-moderate essential hypertension. Hypertension disrupts the left atrial contractile activity and modifies the diastolic characteristics of the left ventricle. Essential hypertension may also affect RA performance. The E/A ratio, the velocity-time integrals (Ei and Ai, respectively), and the total (TTi = Ei + Ai) were calculated using the tricuspid flow velocity curves. The ratio RA active contribution (RAAC) = Ai/TTi was used to express the RAAC. The RA-A/E ratio, RA-Ai, and RAAC were all higher in hypertensives than in controls, whereas RA-TTi was lower; P < 0.0001 for all comparisons. Following treatment, RA dimensions remained unchanged while TTi increased (from 13.2 +/- 1.6 cm to 16.2 +/- 2.0 cm with ramipril and from 12.9 +/- 1.1 cm to 14.4 +/- 1.2 cm with amlodipine, P < 0.001) and RAAC decreased (from 0.19 +/- 0.01 to 0.13 +/- 0.01 with ramipril and from 0.19 +/- 0.01 to 0.16 +/- 0.001). Ramipril significantly reduced RAAC (P < 0.001), and the reduction in LV mass (P < 0.001) and RV relaxation (P < 0.001) had a significant impact. In individuals with essential hypertension, RA function deteriorates. Improved RA function and decreased LV mass without changes in RA dimensions were linked to the drop in arterial BP brought on by antihypertensive therapy. The variations in RA performance were impacted by the LV mass and the RV relaxation[147].
The right atrium is important in PAH, and echocardiography’s measurement of its size is essential for risk assessment. In spite of this, the RA area is still given priority over RA volume index (RAVI) in current standards. Since 2016, worldwide echocardiography associations have recommended the use of RAVI for a more accurate evaluation; this technique goes against their guidelines. According to another study, the HAP risk assessment recommendations should be revised to take a more thorough approach that makes use of measures of the RAVI. It suggests classifying risk as low if RAVI is less than 32 mL/m2, moderate if RAVI is between 32 mL/m2 and 55 mL/m2, and high if RAVI is greater than 55 mL/m2[148].
Patients with PAH have changes in both RV diastolic stiffness and RA function. The effect of RV diastolic stiffness on RA-RV interaction was evaluated. The end-diastolic elastance (Eed) of patients with PAH (n = 94) and controls (n = 31) was compared. Active strain was maintained, whereas RA and RV passive strain decreased as Eed increased. Patients exhibited greater RA active emptying and RA stroke work but lower RV passive filling than controls. Patients with high Eed had less RV active filling, which increased vena cava backflow. About half of the patients with high Eed saw a reduction in Eed following therapy, which was accompanied by significant improvements in RV active filling and stroke volume, as well as bigger reductions in afterload, RV mass, and vena cava backflow when compared to patients whose Eed remained high. RV function alterations are linked to RA function in PAH. Severe RV diastolic stiffness is linked to decreased RV active filling and higher vena cava backflow, despite increased RA stroke effort. Despite therapy, diastolic stiffness persisted in 50% of individuals with elevated baseline Eed. A significant drop in afterload, an increase in RV active filling, and a decrease in vena cava backflow were all associated with a decrease in end-diastolic elastance[149].
Patients with precapillary PH (precPH) have changes in both RV diastolic stiffness and RA function. Using pressure-volume (PV) loops, isolated cardiomyocytes, and histological investigations, this study sought to understand RA function. Patients with precPH exhibit changed RV diastolic stiffness and RA function. The purpose of another study was to use isolated cardiomyocytes, PV loops, and histological investigations to examine RA function. Patients with PrecPH (n = 27) and control participants (n = 9) had RA PV loops built using catheterization and magnetic resonance data. In a larger group of patients with either moderate (n = 39) or severe (n = 41) RV diastolic stiffness, RA stiffness (pressure rise during atrial filling) and right atrioventricular coupling index (RA minimum volume/RV end-diastolic volume) were compared. Cardiomyocytes were separated from RA tissue obtained from patients with precPH (n = 9) undergoing surgery and control persons (n = 6). To investigate RA hypertrophy, capillarization, and fibrosis, autopsy material was obtained from patients with precPH (n = 4) and control persons (n = 6). Three RA cardiac phases (reservoir, passive emptying, and contraction) with dilatation and increased pressure in precPH were displayed by RA PV loops. The right atrioventricular coupling index was lower, and RA stiffness was higher in PrecPH patients with significant RV diastolic stiffness[150].
In precPH, the cardiomyocyte cross-sectional area grew two to three times, while the active tension produced by the sarcomeres remained the same. The cardiomyocytes' passive tension did not rise, but end-stage precPH had interstitial and perivascular fibrosis along with a decrease in capillaries per mm2. In individuals with significant RV diastolic stiffness, RA PV loops indicate atrioventricular uncoupling and exhibit increased RA stiffness. Patients with precPH had hypertrophied isolated RA cardiomyocytes without any intrinsic sarcomeric alterations. Interstitial and perivascular fibrosis are associated with decreased capillary density in end-stage precPH[150].
The measurement of SvO2 uses pulmonary arterial blood, which is a combination of blood from the coronary sinus and the superior and inferior vena cava. It shows how much oxygen is still in the venous circulation and may also show how the systemic oxygen supply and demand are balanced. Because SvO2 reflects both respiratory and circulatory function, it is a crucial clinical parameter for systemic therapy. However, because SvO2 necessitates intrusive sampling from the pulmonary artery, there has been little clinical study and little discussion of it, despite its importance in directing treatment methods. In this case, SvO2 is an important measure of oxygenation in the blood that is going to the lungs. Higher pulmonary artery pressure and, in the event of an intrapulmonary right-to-lefet shunt, higher pulmonary venous pressure might result from a drop in SvO2[151].
Right ventricular failure and mortality are the results of PH, a crippling illness marked by a gradual increase in pulmonary artery pressure. The oxygen saturation of blood returning to the lungs before reaching the alveolo-capillary units is known as SvO2. Clinical results in PH are closely linked to SvO2. It is uncertain how this prognostically significant statistic relates to non-invasive cardiovascular magnetic resonance (CMR) measurements in patients with PH. Another study was to gain an early knowledge of the CMR volumetric and flow characteristics that are most closely linked to SvO2[152].
In every subject, there was no correlation between the LV and RV volumetric functional measures and SvO2. However, there was a negative correlation (R = -0.57; P = 0.01) between SvO2 and RA area. Mean pulmonary artery (MPA) stroke volume was the only other metric that correlated with SvO2 (r = 0.5, P = 0.03). Both parameters showed an independent relationship to SvO2 in stepwise multiple regression. A combined model produced prediction values that showed a strong connection to observed SvO2 (r = 0.73; P < 0.001). SvO2 is independently correlated with both MPA stroke volume and RA area[152].
Although prior research has identified soluble suppression of tumorigenicity-2 (sST2) as a clinical biomarker for PH, the relationship between sST2 and hemodynamic measures in PH has not been thoroughly examined. The purpose of another study was to assess the predictive value of sST2 for mortality in patients with PH as well as the association between sST2 and hemodynamic indicators. Compared to the control group (23.1 ng/mL, P = 0.005), the median concentration of sST2 in patients with PH was 33.1 ng/mL[153].
Additionally, non-survivors in the PH group had a greater level of sST2 than survivors. SvO2 and sST2 were shown to be independent risk variables for survival by Cox regression analysis. Reduced SvO2 and increased sST2 levels in Kaplan-Meier curve studies indicated a bad prognosis for patients with PH. In individuals with PH, lower SvO2 and higher sST2 were both independently linked to higher mortality. In particular, the best predictor of death in patients with PH was the combination of lower SvO2 and greater sST2[153].
Intrapulmonary bronchopulmonary anastomoses (IBAs), which generate intrapulmonary right-to-left shunts, are a reasonably common phenomenon. IBAs are thought to be important in the pathophysiology of heart failure. Using SvO2 as a crucial metric, another study wants to determine how these intrapulmonary right-to-left shunts affect pulmonary arterial and venous pressures in patients with heart failure. SvO2 was strongly and inversely linked with both systolic pulmonary artery pressure (sPAP) and pulmonary artery wedge pressure (PAWP). Nevertheless, there was no significant correlation found between SvO2 and LV end-diastolic pressure (LVEDP). These findings imply that whereas PAWP only has a passive effect on LVEDP, a drop in SvO2 causes an increase in PAWP and sPAP. This condition is probably the result of an intrapulmonary right-to-left shunt brought on by IBAs. In addition to increasing sPAP, a reduction in SvO2 may also enhance PAWP through IBAs[151].
Thermodilution cardiac index (TDCI) and SvO2 are two of the three hemodynamic measurements used in risk assessment of patients with PAH, according to recommendations from the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). When evaluating the prognosis of individuals with either idiopathic or heritable PAH, SvO2 may be a more useful metric than TDCI. It evaluated the association between SvO2 and TDCI in individuals with idiopathic and heritable PAH. There were 158 patients with idiopathic (91%) and heritable (9%) PAH (mean age, 58 ± 17 years; 72% women). TDCI and SvO2 had a moderate correlation (r = 0.50, 95%CI: 0.37-0.62). A reasonable agreement between TDCI and SvO2 was found using weighted kappa (κ = 0.30, 95%CI: 0.18-0.42), with 49% of patients having concordance in risk group allocation. Kaplan-Meier analysis revealed that the SvO2 had an effect on survival (log rank = 0.002), while the TDCI risk group allocation had no effect (log-rank = 0.51). SvO2 (but not TDCI) was linked to mortality using the Cox proportional hazard model after adjusting for age and sex (HR per 1% change, 0.94; 95%CI: 0.91-0.97; P < 0.001). It observed poor agreement in risk score allocation between TDCI and SvO2 using the cutoffs suggested by the ESC/ERS recommendations[154].
An increased risk of developing hypertension is linked to elevated CRP levels, especially > 3 mg/L. Common variables, including obesity, smoking, and sedentary lifestyles, have a significant impact on the relationship between CRP and high BP. Lower CRP levels are common in patients on RAAS inhibitors, indicating that treating hypertension may help lessen inflammation. Some research indicates CRP may be a marker rather than a direct cause of high BP, despite some evidence pointing to a direct causative role in vascular injury. Thus, CRP has been shown to have a causative role in the pa
NLR is regarded as a useful, readily detectable biomarker for determining the risk and severity of hypertension because of its affordability and availability. Both adults and children with hypertension have elevated NLR. Higher chances of cardiovascular mortality are linked to elevated NLR. According to certain research, nebivolol and other antihypertensive medications may lower the NLR ratio[41]. In both clinical practice and epidemiological research, the NLR and PLR can be utilized as trustworthy indicators of inflammation in hypertensives[43].
Due to its ease of detection, accessibility, and affordability, NLR is a frequently used test and a trustworthy indicator of systemic inflammation. Additionally, it may be utilized as a monitoring tool for drugs and disorders. Furthermore, it offers diagnostic and predictive data on subclinical inflammation in addition to traditional risk variables. Furthermore, it offers diagnostic and predictive data on subclinical inflammation in addition to traditional risk variables. Furthermore, NLR’s prognostic value is similar to that of CRP, tumor necrosis factor-α, and interleukin-1 in identifying endothelial dysfunction and subclinical inflammation in a number of clinical trials[33].
MAU has the potential to be an early marker for predicting cardiovascular risk and associated consequences in essential hypertension because of its high correlation with LVH, duration of hypertension, urine Cr, and ACR[52]. For hypertensive individuals, routine testing for MAU using the urine ACR is advised to determine risk and direct treatment. Regardless of BP fluctuation, higher baseline and in-trial NT-proBNP levels predict a higher risk of cardiovascular events. It reduces the requirement for regular echocardiography by identifying diastolic dysfunction in asymptomatic individuals and ruling out significant LV failure. Paradoxically, NT-proBNP levels may be lower in obese people with hypertension. Elevated NT-proBNP levels are linked to greater BP, especially higher pulse pressure. Increased risk of further cardiovascular events and a poor prognosis are linked to higher levels. BNP encourages vasodilation, BP-independent natriuresis and diuresis, as well as reduced preload and sympathetic tone, a clinical indicator of ventricular dysfunction in heart failure[155]. Therefore, among patients with acute severe hypertension, BNP may be useful for the initial evaluation to identify high-risk individuals[66].
By identifying high-risk hypertension individuals who might not exhibit symptoms, ultrasound-based CIMT measurement supports more aggressive, customized treatment strategies. Antihypertensive drugs, especially those that target the renin-angiotensin-aldosterone pathway, have been shown in studies to halt or lessen the course of CIMT, making it a useful tool to track the effectiveness of treatment. CIMT increases with the degree and duration of hypertension and exhibits a linear and continuous relationship with SBP. Compared to people with normotension, a significant portion of hypertensive participants have elevated CIMT. CIMT is closely linked to growing older, and women may experience a greater rate of rise following menopause. People with hypertensive cardiac disease have higher levels of CIMT.
The predictive value of CIMT varies depending on the application and whether or not additional risk variables are taken into account in the prediction, even though those with a greater CIMT are more likely to experience clinical cardiovascular events. Additional information on the clinical utility of CIMT measurements for the patients with hypertension may be obtained through further standardization of measurement protocols, the subsequent establishment of a clear level of CIMT beyond which indicates TOD, and cost-effectiveness analysis of routine CIMT scanning. Finding asymptomatic TOD in patients with hypertension may assist in guiding treatment choices and clarify or reclassify a person’s risk for cardiovascular disease.
One surrogate indicator of TOD in patients with hypertension that is taken into account in guidelines issued by various agencies is CIMT. A summary of the benefits of CIMT for patients with hypertension is provided below[77].
Early detection of subclinical atherosclerosis utilizing IMT assessment and customized treatment approaches is necessary to improve patient outcomes. Healthcare professionals must collaborate to treat individuals with hypertension and increased IMT. A comprehensive strategy is necessary to lower cardiovascular risk in people with hypertension. Treatment planning and cardiovascular risk assessment benefit from routine IMT examination. Anesthesia specialists are also crucial for preserving patient safety and optimizing pain management[82]. According to the findings, it could be useful in identifying a subset of patients with glomerular hyperfiltration who might benefit from antihypertensive medication and have a higher risk of developing CKD[101].
As part of the renal adaptation to decreased perfusion pressure, an initial, frequently transient, fall in GFR might result from intensive BP lowering. BP can be controlled by lowering TG through exercise, weight reduction, cutting back on sweets and alcohol, and increasing fiber. Higher TG levels are strongly correlated with IHT even within “normal” limits, suggesting a continuous association rather than a rigid threshold effect. TGs may be a valuable marker for identifying hypertension individuals at high risk, considering the prognostic relevance of LVH. The sex disparity could point to a potential modulatory effect of TGs on LV structure that is sex-specific[106].
Lifestyle changes, such as cutting back on saturated fat, exercising, and losing weight, can drop BP and TC at the same time. Managing hypertension requires controlling FPG with medication or lifestyle modifications (diet, exercise), with a suggested FPG goal of < 7.0 mmol/L for diabetics. The risk of organ damage, heart disease, and stroke is greatly increased when high BP and higher FPG are combined. The greatest risk of developing hypertension is associated with a continuously rising FPG trajectory over time, as opposed to a single high measurement. Controlled blood glucose levels were strongly correlated with being married, female, using two or more antihypertensive drugs, and having a moderate to high medication-related burden. Both controlled BP and blood glucose levels were positively correlated with employment, lower income, national health insurance registration, single anti-diabetes or anti-hypertensive medications, co-morbidities such as hyperlipidemia or stroke, and moderate to high medication-related burden. Blood glucose and BP were under control in 1 in 5 patients with type 2 DM and hypertension. Therefore, the management of patients with hypertension and type 2 diabetes should take into account the advantages and disadvantages of BP and blood glucose objectives[143].
Increasing RAP in patients with symptomatic TOF predicts future cardiovascular events (prognostication) and corresponds with several aspects of disease severity (risk stratification). The target population of patients with sym
RAP aids in tracking how treatments are working. Antihypertensive medications such as ramipril can enhance RA function, but elevated resting or exercise-induced RAP is indicative of a bad prognosis. RAP is essential for differentiating between pre-capillary and post-capillary PH, in addition to pulmonary artery pressure. Lower values are associated with worse outcomes in individuals with PAH and CTEPH. Mixed venous oxygen saturation serves as a measure of disease severity and survival. There was a negative correlation between PAWP and sPAP, and SvO2. It is a crucial indication of RV function and total cardiac output in individuals with PH since it shows the equilibrium between oxygen supply and consumption. In individuals with PH, lower SvO2 and higher sST2 were both independently linked to higher mortality. In particular, the best predictor of death in patients with PH was the combination of lower SvO2 and greater sST2[153].
These two parameters make up a unique CMR prediction model that shows a strong correlation with the SvO2 determined by an invasive hemodynamic investigation. Before this approach becomes a significant predictive tool for patients with PH, more research is required to ascertain repeatability and reliability[152].
CRP, NLR, MAU, NT-proBNP, CIMT, GFR, TG, BMI, TC, FPG, RAP, and SvO2. Numerous pathophysiology areas, including systemic inflammation, endothelial dysfunction, renal impairment, metabolic dysregulation, and car
Among inflammatory markers, CRP and NLR are linked to a higher risk of cardiovascular events and are powerful indicators of vascular inflammation. Both MAU and decreased GFR are independently associated with poor car
These biomarkers have a number of benefits, such as being widely available (e.g., lipid profile, FPG), cost-effective (e.g., NLR, CRP), and non-invasive (e.g., CIMT, BMI). Many of them make it possible to identify TOD early on, before obvious clinical symptoms show up. Furthermore, there is substantial evidence to support the use of some markers, such NT-proBNP and MAU, in risk prediction and illness monitoring.
Individual biomarkers have limits despite their usefulness. Because they can be high in a variety of inflammatory diseases, CRP and NLR lack specificity. Exercise and infection are examples of temporary variables that may have an impact on MAU. Age, renal function, and obesity can all have an impact on NT-proBNP levels. CIMT measurement may not be standardized and is operator-dependent. Short-term physiological changes and lifestyle have an impact on metabolic indicators like TG and FPG. The normal clinical use of hemodynamic markers such as RAP and SvO2 is limited since they frequently need intrusive monitoring.
Given the multifactorial nature of hypertension, reliance on a single biomarker may not provide comprehensive risk assessment. Combining markers from different pathophysiological domains enhances predictive accuracy. For example, integrating inflammatory (CRP), renal (MAU, GFR), and cardiac (NT-proBNP) markers can improve early detection of TOD and cardiovascular risk stratification.
Recent approaches emphasize the use of multi-marker panels to provide a more holistic evaluation of patients with hypertension. These panels combine biomarkers representing inflammation, renal function, metabolic status, and cardiovascular remodeling. Such integrated models improve prognostic precision by capturing the complex interplay of mechanisms involved in hypertension.
Multi-marker strategies have demonstrated superiority over single-marker models in predicting major adverse cardiovascular events, progression of organ damage, and mortality. For instance, a panel including CRP, NLR, NT-proBNP, and MAU may identify high-risk individuals who would otherwise be underestimated using conventional risk factors alone.
However, challenges remain, including cost-effectiveness, lack of standardized thresholds, and the need for validation in diverse populations. Future research should focus on developing validated scoring systems incorporating these biomarkers and integrating them with clinical and imaging data for personalized risk prediction.
Inflammation-based hematologic markers, especially NPAR, SII, and NLR, may offer useful prognostic data and be useful, non-invasive instruments for forecasting hospital stay length and death in PAH and CTEPH[7]. Additionally, CRP has been linked to cardiac remodeling in response to pressure overload and vascular remodeling in reaction to injury. Novel vascular inflammatory pathways and new targets for vascular pathology therapy may be revealed by emerging data[12]. It is still unclear how CRP functions as a marker or a contributing factor to the development of hypertension and its problems. However, there hasn’t been much research done on how various kinds of anti-hypertensive drugs affect low-grade inflammation as determined by CRP.
Elderly hypertension is favorably correlated with elevated CRP, BMI, and diabetes, and early CRP screening and treatment beginning might help prevent more inflammatory reactions in hypertension[24]. Additionally, NLR can be employed in these individuals as a medication and illness monitoring tool[41]. The potential utility of NLR as a marker for prognostic stratification in diastolic dysfunction, which is linked to poorer cardiovascular outcomes, requires more research[49]. If verified, these new findings imply that NT-proBNP may help evaluate the effectiveness of particular antihypertensive treatments in addition to assisting in the evaluation of cardiovascular disease risk. It appears that further pertinent research is needed[61].
When diagnosing hypertensive heart disease, NT-proBNP levels can be a helpful supplement, especially when evaluating LV hypertrophy and diastolic dysfunction. The function of NT-proBNP levels in the diagnosis of hypertensive heart disease is examined[63]. Additional long-term research is necessary to determine its therapeutic implications[69]. The advantages and function of carotid ultrasonography in people with prehypertension need to be further investigated[85]. Since LVH and artery wall alterations happen simultaneously, managing hypertension should involve treating carotid plaques and elevated CIMT in addition to controlling BP[92]. BP and CIMT are probably independently related in childhood, although it's unclear whether this should be handled[93].
To assess the final impact of BP on kidney function, studies with even longer observation periods are required[102]. In summary, the risk of IHD in those with high TG/Low HDL-C was not predicted by BP. This discovery might help to explain why decreasing BP has not resulted in the anticipated decrease in IHD[105]. In patients with hypertension, clinicians should focus more on the combined assessment of uric acid and lipid profile[109]. A high TyG index was linked to high probabilities of hypertension; however, more research was necessary to determine the exact cause of this association[111]. Given its substantial related illness burden, obesity in older Han Chinese people should receive more attention[116].
In hypertensive people, high TC levels were associated with an increased LTR of CHD mortality. These results may be useful in directing young people at high risk to start therapy or lifestyle modifications[124]. Opportunities to improve the management of concurrent hypertension and hypercholesterolemia continue despite advancements. Concurrent risk factor control and CHD prevention should be enhanced by prescribing antihypertensive and antihyperlipidemic drugs to meet treatment objectives, particularly for elderly patients, minorities, and patients with diabetes of cardiovascular disease patients, and by visiting a doctor at least every 2 years[127].
These results support the significance of integrated screening for hypertension and dyslipidemia in preventative and promotional programs for the aged population[128]. In terms of BP levels, particularly the SBP level and control rates of SBP, DBP, and FPG, comorbid individuals perform worse than those with either condition alone. More confounding variables and national data should be included in future research[130]. To better treat obesity-related illnesses, including diabetes, gout, and cardiac disorders, weight control is advised for both medical students and patients receiving daily medical care[117].
In Chinese women, especially those with greater TC, high fasting blood glucose may be strongly linked to the likelihood of developing new-onset hypertension. To validate our results, more randomised research is required[132].
In real-world community settings, primary care patients with concurrent hypertension and type 2 diabetes continue to face inadequate management of BP and FPG. Routine healthcare planning for community-based cardiovascular prevention should include tailored interventions to enhance patients’ adherence to healthy lifestyles, increase the provision of team-based care, and promote weight control[140].
Given that indexing measures of the right atrium to body size may provide more precision than absolute values, this proposal is based on best clinical practices and complies with international societies’ criteria[148]. SvO2 measures are better than TDCI in predicting long-term mortality in individuals with idiopathic or heritable PAH[154].
To control hypertension and hypertensive damage, the findings may assist in clarifying the pathophysiological mechanism of hypertension and developing new therapeutic approaches that focus on low-grade inflammation[36]. This finding might help clarify the process by which hypertension develops. To manage hypertension and hypertensive damage, new treatment strategies targeting inflammation may be suggested[40].
CRP, NLR, MAU, NT-proBNP, CIMT, GFR, TG, BMI, TC, FPG, RAP, and SvO2 play a significant role in the pathogenesis of hypertension, as explained in Tables 1 and 2. In conclusion, the aforementioned markers collectively highlight that hypertension is not merely a disorder of elevated BP, but a complex, multisystem disease driven by interrelated pathophysiological processes. Elevated CRP and NLR reflect a chronic inflammatory state, while MAU and reduced GFR indicate early renal endothelial dysfunction. Increased NT-proBNP and RAP signify cardiac strain and subclinical heart failure, whereas CIMT represents ongoing vascular remodeling and atherosclerosis. Metabolic factors such as TG, BMI, TC, and FPG further contribute by promoting insulin resistance, lipid abnormalities, and vascular injury. Additionally, impaired SvO2 reflects altered tissue perfusion and oxygen utilization. Hypertension should be understood and managed as a systemic disorder involving inflammation, endothelial dysfunction, metabolic imbalance, and TOD. Therefore, comprehensive risk assessment using these markers is essential for early detection, better prognostication, and more effective, individualized therapeutic strategies beyond simple BP control.
| 1. | Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16:223-237. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 3108] [Cited by in RCA: 2617] [Article Influence: 436.2] [Reference Citation Analysis (2)] |
| 2. | Zhou B, Perel P, Mensah GA, Ezzati M. Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. Nat Rev Cardiol. 2021;18:785-802. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 1227] [Cited by in RCA: 1049] [Article Influence: 209.8] [Reference Citation Analysis (0)] |
| 3. | GBD 2019 Risk Factors Collaborators. Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396:1223-1249. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 7538] [Cited by in RCA: 6361] [Article Influence: 1060.2] [Reference Citation Analysis (30)] |
| 4. | Noohi F, Sarrafzadegan N, Khosravi A, Andalib E; First Recommendation on High Blood Pressure Working Group. The first Iranian recommendations on prevention, evaluation and management of high blood pressure. ARYA Atheroscler. 2012;8:97-118. [PubMed] |
| 5. | Rafaqat S, Nasreen S, Rafaqat S. Role of major adipokines in hypertension: A literature review. World J Hypertens. 2023;11:1-11. [RCA] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 2] [Reference Citation Analysis (0)] |
| 6. | Deaton C, Froelicher ES, Wu LH, Ho C, Shishani K, Jaarsma T. The global burden of cardiovascular disease. Eur J Cardiovasc Nurs. 2011;10 Suppl 2:S5-13. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 84] [Cited by in RCA: 123] [Article Influence: 13.7] [Reference Citation Analysis (0)] |
| 7. | Iancu DG, Mares RG, Cristescu L, Suteu RA, Varga A, Tilea I. Inflammation-Based Hematologic Indices as Prognostic Markers in Pulmonary Arterial and Chronic Thromboembolic Pulmonary Hypertension: A Hypothesis-Generating Registry Study. Int J Mol Sci. 2025;26:10940. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 4] [Reference Citation Analysis (0)] |
| 8. | Rafaqat S, Afzal S, Rafaqat S, Khurshid H, Rafaqat S. Cardiac markers: Role in the pathogenesis of arterial hypertension. World J Hypertens. 2022;10:1-14. [RCA] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 3] [Reference Citation Analysis (1)] |
| 9. | Howard LS. Prognostic factors in pulmonary arterial hypertension: assessing the course of the disease. Eur Respir Rev. 2011;20:236-242. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 45] [Cited by in RCA: 68] [Article Influence: 4.9] [Reference Citation Analysis (0)] |
| 10. | Angeli F, Verdecchia P, Reboldi G. Prognostic impact of hypertension grading. Eur J Intern Med. 2024;126:83-88. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 3] [Reference Citation Analysis (0)] |
| 11. | Verdecchia P. Prognostic value of ambulatory blood pressure: current evidence and clinical implications. Hypertension. 2000;35:844-851. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 354] [Cited by in RCA: 336] [Article Influence: 12.9] [Reference Citation Analysis (1)] |
| 12. | Hage FG. C-reactive protein and hypertension. J Hum Hypertens. 2014;28:410-415. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 166] [Cited by in RCA: 148] [Article Influence: 12.3] [Reference Citation Analysis (0)] |
| 13. | Schillaci G, Pirro M. C-reactive protein in hypertension: clinical significance and predictive value. Nutr Metab Cardiovasc Dis. 2006;16:500-508. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 51] [Cited by in RCA: 50] [Article Influence: 2.5] [Reference Citation Analysis (1)] |
| 14. | Vijayalakshmi S, Pramila K, Lalitha R. The Role of High-sensitivity C-reactive Protein as a Cardiovascular Risk Marker in Essential Hypertension. J Med Sci and Health. 2016;02:23-28. [RCA] [DOI] [Full Text] [Cited by in RCA: 1] [Reference Citation Analysis (0)] |
| 15. | Ghosh T, Ghosh S, Bhattacharjee D. C - reactive protein levels in women with pregnancy induced hypertension. Bangladesh J Med Sci. 1970;10:159-162. [RCA] [DOI] [Full Text] [Cited by in Crossref: 1] [Cited by in RCA: 2] [Article Influence: 0.0] [Reference Citation Analysis (0)] |
| 16. | Bautista LE, López-Jaramillo P, Vera LM, Casas JP, Otero AP, Guaracao AI. Is C-reactive protein an independent risk factor for essential hypertension? J Hypertens. 2001;19:857-861. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 203] [Cited by in RCA: 203] [Article Influence: 8.1] [Reference Citation Analysis (0)] |
| 17. | Sesso HD, Buring JE, Rifai N, Blake GJ, Gaziano JM, Ridker PM. C-reactive protein and the risk of developing hypertension. JAMA. 2003;290:2945-2951. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 787] [Cited by in RCA: 734] [Article Influence: 31.9] [Reference Citation Analysis (0)] |
| 18. | Kullo IJ, Seward JB, Bailey KR, Bielak LF, Grossardt BR, Sheedy PF 2nd, Peyser PA, Turner ST. C-reactive protein is related to arterial wave reflection and stiffness in asymptomatic subjects from the community. Am J Hypertens. 2005;18:1123-1129. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 82] [Cited by in RCA: 81] [Article Influence: 3.9] [Reference Citation Analysis (0)] |
| 19. | Schillaci G, Pirro M, Gemelli F, Pasqualini L, Vaudo G, Marchesi S, Siepi D, Bagaglia F, Mannarino E. Increased C-reactive protein concentrations in never-treated hypertension: the role of systolic and pulse pressures. J Hypertens. 2003;21:1841-1846. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 102] [Cited by in RCA: 103] [Article Influence: 4.5] [Reference Citation Analysis (0)] |
| 20. | Conen D, Zeller A, Pfisterer M, Martina B. Usefulness of B-type natriuretic peptide and C-reactive protein in predicting the presence or absence of left ventricular hypertrophy in patients with systemic hypertension. Am J Cardiol. 2006;97:249-252. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 41] [Cited by in RCA: 43] [Article Influence: 2.2] [Reference Citation Analysis (0)] |
| 21. | Lakoski SG, Cushman M, Palmas W, Blumenthal R, D'Agostino RB Jr, Herrington DM. The relationship between blood pressure and C-reactive protein in the Multi-Ethnic Study of Atherosclerosis (MESA). J Am Coll Cardiol. 2005;46:1869-1874. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 128] [Cited by in RCA: 114] [Article Influence: 5.4] [Reference Citation Analysis (0)] |
| 22. | Chae SC, Lee J, Yang D, Chun B, Kim B, Park W. High-sensitivity C-reactive protein predicts incident hypertension. Int J Cardiol. 2009;137:S60. [RCA] [DOI] [Full Text] [Cited by in RCA: 1] [Reference Citation Analysis (0)] |
| 23. | Fulop T, Rule AD, Schmidt DW, Wiste HJ, Bailey KR, Kullo IJ, Schwartz GL, Mosley TH, Boerwinkle E, Turner ST. C-reactive Protein among Community-Dwelling Hypertensives on Single-agent Antihypertensive Treatment. J Am Soc Hypertens. 2009;3:260-266. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 16] [Cited by in RCA: 17] [Article Influence: 1.0] [Reference Citation Analysis (0)] |
| 24. | He L, Fan C, Li G. The relationship between serum C-reactive protein and senile hypertension. BMC Cardiovasc Disord. 2022;22:500. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 21] [Reference Citation Analysis (0)] |
| 25. | Virdis A, Ghiadoni L, Plantinga Y, Taddei S, Salvetti A. C-reactive protein and hypertension: is there a causal relationship? Curr Pharm Des. 2007;13:1693-1698. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 21] [Cited by in RCA: 27] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
| 26. | Patidar O, Bhargava A, Gupta D. Association of C-reactive protein and arterial hypertension. Int J Adv Med. 2015;2:133. [DOI] [Full Text] |
| 27. | Liu HH, Cao YX, Sun D, Jin JL, Zhang HW, Guo YL, Zhu CG, Wu NQ, Gao Y, Dong QT, Li JJ. High-sensitivity C-reactive protein and hypertension: combined effects on coronary severity and cardiovascular outcomes. Hypertens Res. 2019;42:1783-1793. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 19] [Cited by in RCA: 30] [Article Influence: 4.3] [Reference Citation Analysis (0)] |
| 28. | Blake GJ, Rifai N, Buring JE, Ridker PM. Blood pressure, C-reactive protein, and risk of future cardiovascular events. Circulation. 2003;108:2993-2999. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 231] [Cited by in RCA: 226] [Article Influence: 9.8] [Reference Citation Analysis (0)] |
| 29. | Lakoski SG, Herrington DM, Siscovick DM, Hulley SB. C-reactive protein concentration and incident hypertension in young adults: the CARDIA study. Arch Intern Med. 2006;166:345-349. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 68] [Cited by in RCA: 69] [Article Influence: 3.5] [Reference Citation Analysis (0)] |
| 30. | Bock C, Vogt B, Mattecka S, Yapici G, Brunner P, Fimpel S, Unger JK, Sheriff A. C-Reactive Protein Causes Blood Pressure Drop in Rabbits and Induces Intracellular Calcium Signaling. Front Immunol. 2020;11:1978. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 3] [Cited by in RCA: 9] [Article Influence: 1.5] [Reference Citation Analysis (0)] |
| 31. | Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl Lek Listy. 2021;122:474-488. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 23] [Cited by in RCA: 380] [Article Influence: 76.0] [Reference Citation Analysis (0)] |
| 32. | Imtiaz F, Shafique K, Mirza SS, Ayoob Z, Vart P, Rao S. Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med. 2012;5:2. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 468] [Cited by in RCA: 416] [Article Influence: 29.7] [Reference Citation Analysis (1)] |
| 33. | Balta S, Kurtoglu E, Kucuk U, Demirkol S, Ozturk C. Neutrophil-lymphocyte ratio as an important assessment tool. Expert Rev Cardiovasc Ther. 2014;12:537-538. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 35] [Cited by in RCA: 42] [Article Influence: 3.5] [Reference Citation Analysis (0)] |
| 34. | Zhang X, Wei R, Wang X, Zhang W, Li M, Ni T, Weng W, Li Q. The neutrophil-to-lymphocyte ratio is associated with all-cause and cardiovascular mortality among individuals with hypertension. Cardiovasc Diabetol. 2024;23:117. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 9] [Cited by in RCA: 112] [Article Influence: 56.0] [Reference Citation Analysis (0)] |
| 35. | Jhuang YH, Kao TW, Peng TC, Chen WL, Li YW, Chang PK, Wu LW. Neutrophil to lymphocyte ratio as predictor for incident hypertension: a 9-year cohort study in Taiwan. Hypertens Res. 2019;42:1209-1214. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 17] [Cited by in RCA: 73] [Article Influence: 10.4] [Reference Citation Analysis (0)] |
| 36. | Shukla M, Rudra Dutt Kaushik DA, Verma A, Gadpayle AK. Blood Neutrophil to Lymphocyte Ratio in Newly Detected Hypertension & Its Correlation with Staging. Eur J Cardiovasc Med. 2025;15:152-158. [DOI] [Full Text] |
| 37. | Marwaha V, Alluri S, Alluri V, Laungani Y, Reddy D, Steward R. 3016 - Pilot study of hypertension and neutrophil lymphocyte ratio (NLR) variations in the Afro-caribbean population of curaçao. Exp Hematol. 2024;137:104338. [DOI] [Full Text] |
| 38. | Hou M, Cao L, Ding Y, Chen Y, Wang B, Shen J, Zhou W, Huang J, Xu Q, Lv H, Sun L. Neutrophil to Lymphocyte Ratio Is Increased and Associated With Left Ventricular Diastolic Function in Newly Diagnosed Essential Hypertension Children. Front Pediatr. 2021;9:576005. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 6] [Cited by in RCA: 12] [Article Influence: 2.4] [Reference Citation Analysis (0)] |
| 39. | Yildirim OT, Aydin F, Aydin AH, Dagtekin E, Aksit E, Hasirci SH. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are independent predictors for blood pressure variability. J Hypertens. 2018;36:e12. [RCA] [DOI] [Full Text] [Cited by in Crossref: 2] [Cited by in RCA: 3] [Article Influence: 0.4] [Reference Citation Analysis (0)] |
| 40. | Liu X, Zhang Q, Wu H, Du H, Liu L, Shi H, Wang C, Xia Y, Guo X, Li C, Bao X, Su Q, Sun S, Wang X, Zhou M, Jia Q, Zhao H, Song K, Niu K. Blood Neutrophil to Lymphocyte Ratio as a Predictor of Hypertension. Am J Hypertens. 2015;28:1339-1346. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 71] [Cited by in RCA: 123] [Article Influence: 11.2] [Reference Citation Analysis (0)] |
| 41. | Hussain M, Saeed M, Babar MZM, Atif MA, Akhtar L. Nebivolol Attenuates Neutrophil Lymphocyte Ratio: A Marker of Subclinical Inflammation in Hypertensive Patients. Int J Hypertens. 2017;2017:7643628. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 9] [Cited by in RCA: 11] [Article Influence: 1.2] [Reference Citation Analysis (0)] |
| 42. | Unamba N, Romokere A, James O. The Relationship between Neutrophil to Lymphocyte Ratio and Left Ventricular Function in Drug-naïve Asymptomatic Hypertensive Adults in Port Harcourt, Nigeria. J Adv Med Med Res. 2017;22:1-12. [DOI] [Full Text] |
| 43. | Poihai A, Sivapriya A. A cross-sectional study of neutrophil to lymphocyte ratio as a reliable inflammatory index among hypertensives in Government Rajaji Hospital, Madurai. Int J Res Med Sci. 2022;10:458. [DOI] [Full Text] |
| 44. | Abdulmecit A, Ramazan A, Ertuğrul K, Hakan K. Neutrophil to Lymphocyte Ratio as a Predictor of Left Ventricular Hypertrophy in Patients with Newly Diagnosed Hypertension. J Hypertens Manag. 2019;5:42. [RCA] [DOI] [Full Text] [Cited by in Crossref: 3] [Cited by in RCA: 7] [Article Influence: 1.0] [Reference Citation Analysis (0)] |
| 45. | Sarejloo S, Dehesh M, Fathi M, Khanzadeh M, Lucke-Wold B, Ghaedi A, Khanzadeh S. Meta-analysis of differences in neutrophil to lymphocyte ratio between hypertensive and non-hypertensive individuals. BMC Cardiovasc Disord. 2023;23:283. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 12] [Cited by in RCA: 24] [Article Influence: 8.0] [Reference Citation Analysis (0)] |
| 46. | Gang L, Yanyan Z. Increased neutrophil to lymphocyte ratio in persons suffering from hypertension with hyperhomocysteinemia. Hypertens Res. 2016;39:606-611. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 12] [Cited by in RCA: 15] [Article Influence: 1.5] [Reference Citation Analysis (0)] |
| 47. | Ao G, Wang Y, Qi X, Wang F, Wen H. Association of neutrophil-to-lymphocyte ratio and risk of cardiovascular or all-cause mortality in chronic kidney disease: a meta-analysis. Clin Exp Nephrol. 2021;25:157-165. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 5] [Cited by in RCA: 23] [Article Influence: 3.8] [Reference Citation Analysis (1)] |
| 48. | Hu X, Arthur Vithran DT, Yang Z, Zou T, Tang R, Li H. Investigating the role of age, admission systolic blood pressure, and neutrophil-to-lymphocyte ratio in predicting left ventricular hypertrophy among patients with primary hypertension. J Int Med Res. 2025;53:3000605241310159. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 5] [Reference Citation Analysis (0)] |
| 49. | Karagöz A, Vural A, Günaydın ZY, Bektaş O, Gül M, Çelik A, Uzunoğlu E, Usta S, Sarıtaş A, Elalmış ÖU. The role of neutrophil to lymphocyte ratio as a predictor of diastolic dysfunction in hypertensive patients. Eur Rev Med Pharmacol Sci. 2015;19:433-440. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 1] [Cited by in RCA: 3] [Article Influence: 0.3] [Reference Citation Analysis (0)] |
| 50. | Reboldi G, Gentile G, Angeli F, Verdecchia P. Microalbuminuria and hypertension. Minerva Med. 2005;96:261-275. [PubMed] |
| 51. | Bianchi S, Bigazzi R, Campese VM. Microalbuminuria in essential hypertension: significance, pathophysiology, and therapeutic implications. Am J Kidney Dis. 1999;34:973-995. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 108] [Cited by in RCA: 106] [Article Influence: 3.9] [Reference Citation Analysis (0)] |
| 52. | Pruthvi AR, Madhusudan J. Microalbuminuria in Non-Diabetic Patients with Essential hypertension and its Correlation with Left Ventricular Mass Index: A Cross-Sectional Study. Eur J Cardiovasc Med. 2025;15:36 -367. [DOI] [Full Text] |
| 53. | Khattak MS, Shah NU, Khan MS, Haq IU, Hussain S, Pervez N. Frequency of Microalbuminuria in Essential Hypertension in tertiary care hospital in Southern District of Khyber Pakhtunkhwa. Isra Med J. 2021;13. |
| 54. | Alharf AA, Cleland S, Webster J, McInnes GT, Padmanabhan S. Microalbuminuria in subjects with hypertension attending specialist blood pressure clinics. J Hum Hypertens. 2016;30:527-533. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 3] [Cited by in RCA: 8] [Article Influence: 0.7] [Reference Citation Analysis (0)] |
| 55. | Bhowmick D, Chakraborty S, Ali MDH, Ghosh K, Acharyya A, Karmakar PS, Banerjee S. Microalbuminuria in hypertension and its relationship to target organ damage: A cross-sectional observational study in a tertiary hospital in Eastern India. J Clin Sci Res. 2023;12:134-139. [DOI] [Full Text] |
| 56. | Rodicio JL, Campo C, Ruilope LM. Microalbuminuria in essential hypertension. Kidney Int Suppl. 1998;68:S51-S54. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 36] [Cited by in RCA: 36] [Article Influence: 1.3] [Reference Citation Analysis (0)] |
| 57. | Nadir MA, Witham MD, Szwejkowski BR, Struthers AD. Meta-analysis of B-type natriuretic peptide's ability to identify stress induced myocardial ischemia. Am J Cardiol. 2011;107:662-667. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 28] [Cited by in RCA: 29] [Article Influence: 1.9] [Reference Citation Analysis (1)] |
| 58. | Clerico A, Giannoni A, Vittorini S, Emdin M. The paradox of low BNP levels in obesity. Heart Fail Rev. 2012;17:81-96. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 91] [Cited by in RCA: 108] [Article Influence: 7.2] [Reference Citation Analysis (0)] |
| 59. | Martinez-Rumayor A, Richards AM, Burnett JC, Januzzi JL Jr. Biology of the natriuretic peptides. Am J Cardiol. 2008;101:3-8. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 150] [Cited by in RCA: 152] [Article Influence: 8.4] [Reference Citation Analysis (1)] |
| 60. | Nicoli CD, Plante TB, Long DL, Judd SE, McClure LA, Arora P, Cushman M. N-Terminal Pro-B-Type Natriuretic Peptide and Longitudinal Risk of Hypertension. Am J Hypertens. 2021;34:476-483. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 6] [Cited by in RCA: 6] [Article Influence: 1.2] [Reference Citation Analysis (0)] |
| 61. | Welsh P, Poulter NR, Chang CL, Sever PS, Sattar N; ASCOT Investigators. The value of N-terminal pro-B-type natriuretic peptide in determining antihypertensive benefit: observations from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Hypertension. 2014;63:507-513. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 22] [Cited by in RCA: 26] [Article Influence: 2.2] [Reference Citation Analysis (0)] |
| 62. | Rivera M, Taléns-Visconti R, Salvador A, Bertomeu V, Miró V, García de Burgos F, Climent V, Cortés R, Payá R, Pérez-Boscá JL, Mainar L, Jordán A, Sogorb F, Cosín J, Mora V, Diago JL, Marín F. NT-proBNP Levels and Hypertension. Their Importance in the Diagnosis of Heart Failure. Rev Esp Cardiol. 2004;57:396-402. [DOI] [Full Text] |
| 63. | Mouzarou A, Hadjigeorgiou N, Melanarkiti D, Plakomyti TE. The Role of NT-proBNP Levels in the Diagnosis of Hypertensive Heart Disease. Diagnostics (Basel). 2025;15:113. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 23] [Reference Citation Analysis (0)] |
| 64. | Macheret F, Heublein D, Costello-Boerrigter LC, Boerrigter G, McKie P, Bellavia D, Mangiafico S, Ikeda Y, Bailey K, Scott CG, Sandberg S, Chen HH, Malatino L, Redfield MM, Rodeheffer R, Burnett J Jr, Cataliotti A. Human hypertension is characterized by a lack of activation of the antihypertensive cardiac hormones ANP and BNP. J Am Coll Cardiol. 2012;60:1558-1565. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 63] [Cited by in RCA: 82] [Article Influence: 5.9] [Reference Citation Analysis (0)] |
| 65. | Seven E, Husemoen LL, Ibsen H, Friedrich N, Nauck M, Wachtell K, Linneberg A, Jeppesen JL. Higher serum concentrations of N-terminal pro-B-type natriuretic peptide associate with prevalent hypertension whereas lower associate with incident hypertension. PLoS One. 2015;10:e0117864. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 13] [Cited by in RCA: 13] [Article Influence: 1.2] [Reference Citation Analysis (0)] |
| 66. | Kim BS, Lee Y, Lim YH, Shin J, Shin JH. Association between B-type natriuretic peptide and long-term mortality in patients with acute severe hypertension visiting the emergency department. Sci Rep. 2022;12:21001. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 4] [Reference Citation Analysis (0)] |
| 67. | Hsiao CH, Yang CF, Wang JH, Hsu BG. Serum N-Terminal Pro-B-Type Natriuretic Peptide Level is Negatively Associated with Vascular Reactivity Index by Digital Thermal Monitoring in Patients with Hypertension. Rev Cardiovasc Med. 2024;25:214. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 2] [Reference Citation Analysis (0)] |
| 68. | Jabeen M, Khoja A, Iqbal A, Iftikhar U, Furqan M. Brain natriuretic peptide, systolic and diastolic blood pressures. J Ayub Med Coll Abbottabad. 2008;20:134-136. [PubMed] |
| 69. | Imamura T, Kinugawa K. Implication of sacubitril/valsartan on N-terminal pro B-type natriuretic peptide levels in hypertensive patients. Ann Palliat Med. 2022;11:2856-2861. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 5] [Cited by in RCA: 6] [Article Influence: 1.5] [Reference Citation Analysis (0)] |
| 70. | Uraizee I, Cheng S, Hung CL, Verma A, Thomas JD, Zile MR, Aurigemma GP, Solomon SD. Relation of N-terminal pro-B-type natriuretic peptide with diastolic function in hypertensive heart disease. Am J Hypertens. 2013;26:1234-1241. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 13] [Cited by in RCA: 16] [Article Influence: 1.2] [Reference Citation Analysis (0)] |
| 71. | Carpenter M, Sinclair H, Kunadian V. Carotid Intima Media Thickness and Its Utility as a Predictor of Cardiovascular Disease: A Review of Evidence. Cardiol Rev. 2016;24:70-75. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 40] [Cited by in RCA: 56] [Article Influence: 5.6] [Reference Citation Analysis (0)] |
| 72. | Centurión OA. Carotid Intima-Media Thickness as a Cardiovascular Risk Factor and Imaging Pathway of Atherosclerosis. Crit Pathw Cardiol. 2016;15:152-160. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 18] [Cited by in RCA: 19] [Article Influence: 1.9] [Reference Citation Analysis (0)] |
| 73. | Lorenz MW, Polak JF, Kavousi M, Mathiesen EB, Völzke H, Tuomainen TP, Sander D, Plichart M, Catapano AL, Robertson CM, Kiechl S, Rundek T, Desvarieux M, Lind L, Schmid C, DasMahapatra P, Gao L, Ziegelbauer K, Bots ML, Thompson SG; PROG-IMT Study Group. Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data. Lancet. 2012;379:2053-2062. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 462] [Cited by in RCA: 461] [Article Influence: 32.9] [Reference Citation Analysis (5)] |
| 74. | Sedding DG, Boyle EC, Demandt JAF, Sluimer JC, Dutzmann J, Haverich A, Bauersachs J. Vasa Vasorum Angiogenesis: Key Player in the Initiation and Progression of Atherosclerosis and Potential Target for the Treatment of Cardiovascular Disease. Front Immunol. 2018;9:706. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 106] [Cited by in RCA: 190] [Article Influence: 23.8] [Reference Citation Analysis (19)] |
| 75. | le Noble FAC, Mourad JJ, Levy BI, Struijker-Boudier HAJ. VEGF (Vascular Endothelial Growth Factor) Inhibition and Hypertension: Does Microvascular Rarefaction Play a Role? Hypertension. 2023;80:901-911. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 31] [Reference Citation Analysis (0)] |
| 76. | Shimizu Y, Kawashiri SY, Kiyoura K, Nobusue K, Yamanashi H, Nagata Y, Maeda T. Gamma-glutamyl transpeptidase (γ-GTP) has an ambivalent association with hypertension and atherosclerosis among elderly Japanese men: a cross-sectional study. Environ Health Prev Med. 2019;24:69. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 14] [Cited by in RCA: 29] [Article Influence: 4.1] [Reference Citation Analysis (0)] |
| 77. | Magnussen CG. Carotid artery intima-media thickness and hypertensive heart disease: a short review. Clin Hypertens. 2017;23:7. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 14] [Cited by in RCA: 20] [Article Influence: 2.2] [Reference Citation Analysis (0)] |
| 78. | Naseh G, Fard MM, Kazemi T, Mirgholami A, Hashemi N, Saburi A. Comparison of Carotid Intima-media Thickness in Hypertensive Patients and Control Group. J Cardiovasc Echogr. 2016;26:48-51. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 2] [Cited by in RCA: 3] [Article Influence: 0.3] [Reference Citation Analysis (0)] |
| 79. | Ren L, Shi M, Wu Y, Ni J, Bai L, Lu H, Tu J, Wang J, Ning X. Correlation between hypertension and common carotid artery intima-media thickness in rural China: a population-based study. J Hum Hypertens. 2018;32:548-554. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 11] [Cited by in RCA: 16] [Article Influence: 2.0] [Reference Citation Analysis (0)] |
| 80. | Sun P, Liu L, Liu C, Zhang Y, Yang Y, Qin X, Li J, Cao J, Zhang Y, Zhou Z, Xu X, Huo Y. Carotid Intima-Media Thickness and the Risk of First Stroke in Patients With Hypertension. Stroke. 2020;51:379-386. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 18] [Cited by in RCA: 39] [Article Influence: 6.5] [Reference Citation Analysis (0)] |
| 81. | Shimizu Y. Progression of Carotid Intima-Media Thickness Partly Indicates the Prevention of Hypertension among Older Individuals in the General Population. Life (Basel). 2023;13:1588. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 10] [Reference Citation Analysis (0)] |
| 82. | Khan JK. Intima media thickness as an indicator of cardiovascular risk in hypertensive patients. Pol Ann Med. 2025;32:246-250. [DOI] [Full Text] |
| 83. | Takase H, Sugiura T, Murai S, Yamashita S, Ohte N, Dohi Y. Carotid intima-media thickness is a novel predictor of new onset of hypertension in normotensive subjects. Medicine (Baltimore). 2017;96:e7710. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 10] [Cited by in RCA: 16] [Article Influence: 1.8] [Reference Citation Analysis (0)] |
| 84. | Morelli M, Tognola C, Garofani I, Le Van M, Tacchetto A, Bellomare M, Algeri M, Shkodra A, Giannattasio C, Maloberti A. Association Between Carotid Intima-Media Thickness and Novel Lipid Parameters in Hypertensive Patients. High Blood Press Cardiovasc Prev. 2025;32:335-341. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 9] [Reference Citation Analysis (0)] |
| 85. | Lee YH, Kweon SS, Choi JS, Rhee JA, Choi SW, Ryu SY, Shin MH. [Association of blood pressure levels with carotid intima-media thickness and plaques]. J Prev Med Public Health. 2009;42:298-304. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 2] [Cited by in RCA: 4] [Article Influence: 0.2] [Reference Citation Analysis (0)] |
| 86. | Liu J, Lin Q, Guo D, Yang Y, Zhang X, Tu J, Ning X, Song Y, Wang J. Association Between Pulse Pressure and Carotid Intima-Media Thickness Among Low-Income Adults Aged 45 Years and Older: A Population-Based Cross-Sectional Study in Rural China. Front Cardiovasc Med. 2020;7:547365. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 3] [Cited by in RCA: 8] [Article Influence: 1.3] [Reference Citation Analysis (0)] |
| 87. | Chen YC, Guo X, Raffel LJ, Xiang AH, Fang B, Hsueh WA, Taylor KD, Buchanan TA, Hodis HN, Rotter JI. Carotid intima-media thickness (cIMT) cosegregates with blood pressure and renal function in hypertensive Hispanic families. Atherosclerosis. 2008;198:160-165. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 7] [Cited by in RCA: 7] [Article Influence: 0.4] [Reference Citation Analysis (0)] |
| 88. | AL-Auqbi TF, Al-Sabbagh AA, Al-Karawi IN, Maj B. Effect of hypertension on the carotid artery intima media thickness (IMT) in patients with type 2 diabetes mellitus-across sectional study. Int J Diabetes Res. 2014;3:66-70. [DOI] [Full Text] |
| 89. | Lim SM, Kim HC, Lee HS, Lee JY, Suh M, Ahn SV. Association between blood pressure and carotid intima-media thickness. J Pediatr. 2009;154:667-671. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 20] [Cited by in RCA: 21] [Article Influence: 1.2] [Reference Citation Analysis (0)] |
| 90. | Kanwal HI, Shahid M, Bacha R. Sonographic Assessment of Intima-Media Thickness of Carotid Arteries in Hypertensive and Diabetic Volunteers. J Diagn Med Sonog. 2024;40:20-27. [DOI] [Full Text] |
| 91. | Lemne C, Jogestrand T, de Faire U. Carotid intima-media thickness and plaque in borderline hypertension. Stroke. 1995;26:34-39. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 113] [Cited by in RCA: 111] [Article Influence: 3.6] [Reference Citation Analysis (0)] |
| 92. | Khutan H, Aggarwal S, Kajal KS, Garg R, Kaur R, Kaur A. Study of carotid intimal medial thickness in essential hypertension with or without left ventricular hypertrophy. Ann Afr Med. 2017;16:192-195. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 3] [Cited by in RCA: 9] [Article Influence: 1.0] [Reference Citation Analysis (0)] |
| 93. | Day TG, Park M, Kinra S. The association between blood pressure and carotid intima-media thickness in children: a systematic review. Cardiol Young. 2017;27:1295-1305. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 33] [Cited by in RCA: 40] [Article Influence: 4.4] [Reference Citation Analysis (0)] |
| 94. | Mathisen U, Melsom T, Ingebretsen O, Jenssen T, Njølstad I, Solbu M, Toft I, Eriksen B. The relationship between glomerular filtration rate measured as iohexol-clearance and ambulatory blood pressure in the general population: PP.9.364. J Hypertens. 2010;28:e159. [RCA] [DOI] [Full Text] [Cited by in RCA: 1] [Reference Citation Analysis (0)] |
| 95. | Collard D, Brouwer TF, Olde Engberink RHG, Zwinderman AH, Vogt L, van den Born BH. Initial Estimated Glomerular Filtration Rate Decline and Long-Term Renal Function During Intensive Antihypertensive Therapy: A Post Hoc Analysis of the SPRINT and ACCORD-BP Randomized Controlled Trials. Hypertension. 2020;75:1205-1212. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 32] [Cited by in RCA: 50] [Article Influence: 8.3] [Reference Citation Analysis (4)] |
| 96. | Gela YY, Belay DG, Belsti Y, Getahun AB, Getnet M, Bitew DA, Terefe B, Chilot D, Diress M, Akalu Y. Impaired glomerular filtration rate and associated factors among diabetic mellitus patients with hypertension in referral hospitals, Amhara Regional State, Ethiopia. Sci Rep. 2024;14:25143. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 2] [Reference Citation Analysis (0)] |
| 97. | Segura J, Campo C, Ruilope LM. Effect of proteinuria and glomerular filtration rate on cardiovascular risk in essential hypertension. Kidney Int Suppl. 2004;S45-S49. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 32] [Cited by in RCA: 31] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
| 98. | Yu Z, Rebholz CM, Wong E, Chen Y, Matsushita K, Coresh J, Grams ME. Association Between Hypertension and Kidney Function Decline: The Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis. 2019;74:310-319. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 45] [Cited by in RCA: 60] [Article Influence: 8.6] [Reference Citation Analysis (0)] |
| 99. | Truscello L, Nobre D, Sabaratnam V, Bonny O, Wuerzner G, Burnier M, Fakhouri F, Pruijm M, Zanchi A. Blood pressure and vascular determinants of glomerular filtration rate decline in diabetic kidney disease. Front Cardiovasc Med. 2023;10:1230227. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 3] [Reference Citation Analysis (0)] |
| 100. | Yui Y, Kodama K, Hirayama A, Hosoda S, Kawai C; Japan Multicenter Investigation for Cardiovascular DiseaseB (JMIC-B) Study Group. Estimated glomerular filtration rate reversal by blood pressure lowering in chronic kidney disease: Japan Multicenter Investigation for Cardiovascular DiseaseB CKD study. J Clin Hypertens (Greenwich). 2013;15:171-175. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 1] [Cited by in RCA: 2] [Article Influence: 0.1] [Reference Citation Analysis (0)] |
| 101. | Palatini P, Dorigatti F, Saladini F, Benetti E, Mos L, Mazzer A, Zanata G, Garavelli G, Casiglia E. Factors associated with glomerular hyperfiltration in the early stage of hypertension. Am J Hypertens. 2012;25:1011-1016. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 28] [Cited by in RCA: 38] [Article Influence: 2.7] [Reference Citation Analysis (0)] |
| 102. | Eriksen BO, Stefansson VT, Jenssen TG, Mathisen UD, Schei J, Solbu MD, Wilsgaard T, Melsom T. Blood pressure and age-related GFR decline in the general population. BMC Nephrol. 2017;18:77. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 28] [Cited by in RCA: 36] [Article Influence: 4.0] [Reference Citation Analysis (0)] |
| 103. | Reboldi G, Verdecchia P, Fiorucci G, Beilin LJ, Eguchi K, Imai Y, Kario K, Ohkubo T, Pierdomenico SD, Schwartz JE, Wing L, Saladini F, Palatini P. Glomerular hyperfiltration is a predictor of adverse cardiovascular outcomes. Kidney Int. 2018;93:195-203. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 46] [Cited by in RCA: 75] [Article Influence: 8.3] [Reference Citation Analysis (0)] |
| 104. | Ha HJ, Kang MK, Kim JH, Choi YH, Song TJ. Renal hyperfiltration is associated with a reduced incidence of hypertension in individuals younger than 70. Sci Rep. 2025;15:12573. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 3] [Reference Citation Analysis (0)] |
| 105. | Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. High triglycerides and low HDL cholesterol and blood pressure and risk of ischemic heart disease. Hypertension. 2000;36:226-232. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 54] [Cited by in RCA: 49] [Article Influence: 1.9] [Reference Citation Analysis (0)] |
| 106. | Pietri P, Georgiopoulos G, Tsiachris D, Kordalis A, Vlachopoulos C, Vyssoulis G, Stefanadis C. Triglycerides are related to left ventricular mass in hypertensive patients independently of other cardiometabolic risk factors: the effect of gender. Sci Rep. 2020;10:13253. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 4] [Cited by in RCA: 16] [Article Influence: 2.7] [Reference Citation Analysis (0)] |
| 107. | Kim BY, Bang NY, Baik DI, Jung KY, Park J. Correlation between Systolic Blood Pressure and Triglyceride Level in the Uzbekistan Population. Ewha Med J. 2021;44:19-25. [DOI] [Full Text] |
| 108. | Goto K. Triglyceride, an Independent Risk Factor for New-Onset Hypertension: A Perspective. Endocr Metab Immune Disord Drug Targets. 2023;23:1483-1490. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 6] [Reference Citation Analysis (0)] |
| 109. | Seki S, Taniguchi I, Yoshimura M. Clinical significance of triglyceride and uric acid in untreated hypertension: PP.7.264. J Hypertens. 2010;28:e129. [RCA] [DOI] [Full Text] [Cited by in Crossref: 1] [Cited by in RCA: 1] [Article Influence: 0.1] [Reference Citation Analysis (0)] |
| 110. | Huldani, Kaidah S, Adiputro DL, Achmad H, Sukmana BI, Putri DKT, Wasiaturrahmah Y, Dewi RK, Aspriyanto D, Hatta I, Winias S, Pratiwi AR, Sari E, Putra AP, Manik ADMC, Zailin K, Wardani IK. Effect of Total Cholesterol Levels and Triglycerides on Blood Pressure Hypertension Patients Overview against Puskesmas Banjar Ethnic Group in Cempaka Banjarmasin. Sys Rev Pharm. 2020;11:384-389. [DOI] [Full Text] |
| 111. | Wang S, Wang Q, Yan X. Association between triglyceride-glucose index and hypertension: a cohort study based on the China Health and Nutrition Survey (2009-2015). BMC Cardiovasc Disord. 2024;24:168. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 1] [Cited by in RCA: 16] [Article Influence: 8.0] [Reference Citation Analysis (0)] |
| 112. | Kurtkulagi O, Aktas G, Taslamacioglu Duman T, Bilgin S, Atak Tel BM, Kahveci G. Correlation between serum triglyceride to HDL cholesterol ratio and blood pressure in patients with primary hypertension. Precis Med Sci. 2022;11:100-105. [RCA] [DOI] [Full Text] [Cited by in RCA: 17] [Reference Citation Analysis (0)] |
| 113. | Tohidi M, Hatami M, Hadaegh F, Azizi F. Triglycerides and triglycerides to high-density lipoprotein cholesterol ratio are strong predictors of incident hypertension in Middle Eastern women. J Hum Hypertens. 2012;26:525-532. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 54] [Cited by in RCA: 72] [Article Influence: 4.8] [Reference Citation Analysis (0)] |
| 114. | Pray R, Riskin S. The History and Faults of the Body Mass Index and Where to Look Next: A Literature Review. Cureus. 2023;15:e48230. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 39] [Cited by in RCA: 31] [Article Influence: 10.3] [Reference Citation Analysis (0)] |
| 115. | Landi F, Calvani R, Picca A, Tosato M, Martone AM, Ortolani E, Sisto A, D'Angelo E, Serafini E, Desideri G, Fuga MT, Marzetti E. Body Mass Index is Strongly Associated with Hypertension: Results from the Longevity Check-up 7+ Study. Nutrients. 2018;10:1976. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 93] [Cited by in RCA: 142] [Article Influence: 17.8] [Reference Citation Analysis (0)] |
| 116. | Zhang H, Li G, Li F, Jiang J. Body Mass Index and the Risk of Hypertension-Diabetes Comorbidity in Elderly Population: A Prospective Cohort in China. Glob Heart. 2025;20:97. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 1] [Cited by in RCA: 3] [Article Influence: 3.0] [Reference Citation Analysis (0)] |
| 117. | Song L, Li J, Yu S, Cai Y, He H, Lun J, Zheng L, Ye J. Body Mass Index is Associated with blood pressure and vital capacity in medical students. Lipids Health Dis. 2023;22:174. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 13] [Reference Citation Analysis (0)] |
| 118. | Shihab HM, Meoni LA, Chu AY, Wang NY, Ford DE, Liang KY, Gallo JJ, Klag MJ. Body mass index and risk of incident hypertension over the life course: the Johns Hopkins Precursors Study. Circulation. 2012;126:2983-2989. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 167] [Cited by in RCA: 225] [Article Influence: 16.1] [Reference Citation Analysis (3)] |
| 119. | Khalid F, Siddique A, Siddiqui JA, Panhwar G, Singh S, Anwar A, Hashmi AA. Correlation Between Body Mass Index and Blood Pressure Levels Among Hypertensive Patients: A Gender-Based Comparison. Cureus. 2020;12:e10974. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 1] [Cited by in RCA: 3] [Article Influence: 0.5] [Reference Citation Analysis (0)] |
| 120. | Kaur M. Correlation between body mass index and blood pressure in adolescents. Pak J Physiol. 2016;12:47-50. [DOI] [Full Text] |
| 121. | Kosami K, Kuwabara M, Okayama A, Ae R. Body Mass Index and Weight Change as Predictors of Hypertension Development: A Sex-Specific Analysis. Nutrients. 2024;17:119. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 1] [Cited by in RCA: 8] [Article Influence: 4.0] [Reference Citation Analysis (0)] |
| 122. | Yuan L, Qu C, Zhao J, Lu L, Chen J, Xu Y, Li X, Mao T, Yang G, Zhen S, Liu S. Dose-response relationship between body mass index and hypertension: A cross-sectional study from Eastern China. Prev Med Rep. 2024;46:102852. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 2] [Reference Citation Analysis (0)] |
| 123. | Tesfaye F, Nawi NG, Van Minh H, Byass P, Berhane Y, Bonita R, Wall S. Association between body mass index and blood pressure across three populations in Africa and Asia. J Hum Hypertens. 2007;21:28-37. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 129] [Cited by in RCA: 138] [Article Influence: 6.9] [Reference Citation Analysis (0)] |
| 124. | Satoh M, Ohkubo T, Asayama K, Murakami Y, Sugiyama D, Waki T, Tanaka-Mizuno S, Yamada M, Saitoh S, Sakata K, Irie F, Sairenchi T, Ishikawa S, Kiyama M, Okayama A, Miura K, Imai Y, Ueshima H, Okamura T; Evidence for Cardiovascular Prevention from Observational Cohorts in Japan (EPOCH-JAPAN) Research Group. A Combination of Blood Pressure and Total Cholesterol Increases the Lifetime Risk of Coronary Heart Disease Mortality: EPOCH-JAPAN. J Atheroscler Thromb. 2021;28:6-24. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 13] [Cited by in RCA: 18] [Article Influence: 3.6] [Reference Citation Analysis (0)] |
| 125. | Chen H, Chen Y, Wu W, Cai Z, Chen Z, Yan X, Wu S. Total cholesterol, arterial stiffness, and systolic blood pressure: a mediation analysis. Sci Rep. 2021;11:1330. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 6] [Cited by in RCA: 25] [Article Influence: 5.0] [Reference Citation Analysis (0)] |
| 126. | Sinaga EM, Musyabiq S. The Relationship of Cholesterol Levels with Hypertension. Med Prof J Lampung. 2024;14:260-265. |
| 127. | Egan BM, Li J, Qanungo S, Wolfman TE. Blood pressure and cholesterol control in hypertensive hypercholesterolemic patients: national health and nutrition examination surveys 1988-2010. Circulation. 2013;128:29-41. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 99] [Cited by in RCA: 110] [Article Influence: 8.5] [Reference Citation Analysis (0)] |
| 128. | Pramono A, Sari QIP. The Relationship Between Cholesterol Levels and Blood Pressure in the Elderly. J Innov Health Inform. 2025;5:99-104. [DOI] [Full Text] |
| 129. | Luo B, Feng L, Bi Q, Shi R, Cao H, Zhang Y. Fasting Plasma Glucose and Glycated Hemoglobin Levels as Risk Factors for the Development of Hypertension: A Retrospective Cohort Study. Diabetes Metab Syndr Obes. 2023;16:1791-1798. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 1] [Cited by in RCA: 4] [Article Influence: 1.3] [Reference Citation Analysis (0)] |
| 130. | Xu L, Wen X, Yang Y, Cui D. Trends and Comparisons of Blood Pressure and Fasting Plasma Glucose in Patients with Hypertension, Diabetes, and Comorbidity: 4-Year Follow-Up Data. Risk Manag Healthc Policy. 2022;15:2221-2232. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 3] [Cited by in RCA: 3] [Article Influence: 0.8] [Reference Citation Analysis (0)] |
| 131. | Lv Y, Yao Y, Ye J, Guo X, Dou J, Shen L, Zhang A, Xue Z, Yu Y, Jin L. Association of Blood Pressure with Fasting Blood Glucose Levels in Northeast China: A Cross-Sectional Study. Sci Rep. 2018;8:7917. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 17] [Cited by in RCA: 22] [Article Influence: 2.8] [Reference Citation Analysis (0)] |
| 132. | Liu J, Cheng NN, Zhou ZY, Zhang Y, Yang J, Liu LS, Song Y, Huang X, Tang GF, Wang BY, Qin XH, Xu XP, Kong XQ. Effect of fasting blood glucose on risk of new-onset hypertension in rural Chinese population: a 15-year follow-up cohort. BMC Cardiovasc Disord. 2021;21:531. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 7] [Reference Citation Analysis (1)] |
| 133. | Roengrit T, Sri-Amad R, Huipao N, Phababpha S, Prasertsri P. Impact of Fasting Blood Glucose Levels on Blood Pressure Parameters among Older Adults with Prediabetes. ScientificWorldJournal. 2023;2023:1778371. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 3] [Reference Citation Analysis (0)] |
| 134. | Lou Y, Zhang Y, Zhao P, Qin P, Wang C, Ma J, Peng X, Chen H, Zhao D, Xu S, Wang L, Zhang M, Hu D, Hu F. Association of fasting plasma glucose change trajectory and risk of hypertension: a cohort study in China. Endocr Connect. 2022;11:e210464. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 1] [Cited by in RCA: 7] [Article Influence: 1.8] [Reference Citation Analysis (0)] |
| 135. | Henry P, Thomas F, Benetos A, Guize L. Impaired fasting glucose, blood pressure and cardiovascular disease mortality. Hypertension. 2002;40:458-463. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 81] [Cited by in RCA: 76] [Article Influence: 3.2] [Reference Citation Analysis (0)] |
| 136. | Zi H, Wang XJ, Zhao MJ, Huang Q, Wang XH, Zeng XT. Fasting blood glucose level and hypertension risk in aging benign prostatic hyperplasia patients. Aging (Albany NY). 2019;11:4438-4445. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 9] [Cited by in RCA: 10] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
| 137. | Geva M, Shlomai G, Berkovich A, Maor E, Leibowitz A, Tenenbaum A, Grossman E. The association between fasting plasma glucose and glycated hemoglobin in the prediabetes range and future development of hypertension. Cardiovasc Diabetol. 2019;18:53. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 15] [Cited by in RCA: 36] [Article Influence: 5.1] [Reference Citation Analysis (0)] |
| 138. | Zhao L, Ouyang J, Song Y, Qu H, Gao Z. History of Hypertension From Childhood and Fasting Blood Glucose Levels in Adulthood: The Bogalusa Study. J Diabetes. 2025;17:e70155. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 1] [Reference Citation Analysis (0)] |
| 139. | Ahn SK, Lee JM, Ji SM, Kim KH, Park JH, Hyun MK. Incidence Hypertension and Fasting Blood Glucose from Real-World Data: Retrospective Cohort for 7-Years Follow-Up. Int J Environ Res Public Health. 2021;18:2085. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 1] [Cited by in RCA: 11] [Article Influence: 2.2] [Reference Citation Analysis (0)] |
| 140. | Yu X, Li YT, Cheng H, Zhu S, Hu XJ, Wang JJ, Mohammed BH, Xie YJ, Hernandez J, Wu HF, Wang HHX. Longitudinal changes in blood pressure and fasting plasma glucose among 5,398 primary care patients with concomitant hypertension and diabetes: An observational study and implications for community-based cardiovascular prevention. Front Cardiovasc Med. 2023;10:1120543. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 1] [Reference Citation Analysis (0)] |
| 141. | Si Y, Wang A, Yang Y, Liu H, Gu S, Mu Y, Lyu Z. Fasting Blood Glucose and 2-h Postprandial Blood Glucose Predict Hypertension: A Report from the REACTION Study. Diabetes Ther. 2021;12:1117-1128. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 4] [Cited by in RCA: 8] [Article Influence: 1.6] [Reference Citation Analysis (0)] |
| 142. | Janghorbani M, Bonnet F, Amini M. Glucose and the risk of hypertension in first-degree relatives of patients with type 2 diabetes. Hypertens Res. 2015;38:349-354. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 8] [Cited by in RCA: 16] [Article Influence: 1.5] [Reference Citation Analysis (0)] |
| 143. | Alhassan Y, Kwakye AO, Dwomoh AK, Baah-Nyarkoh E, Ganu VJ, Appiah B, Kretchy IA. Determinants of blood pressure and blood glucose control in patients with co-morbid hypertension and type 2 diabetes mellitus in Ghana: A hospital-based cross-sectional study. PLOS Glob Public Health. 2022;2:e0001342. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 10] [Reference Citation Analysis (0)] |
| 144. | Korhonen P, Aarnio P, Saaresranta T, Jaatinen P, Kantola I. Glucose homeostasis in hypertensive subjects. Hypertension. 2008;51:945-949. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 23] [Cited by in RCA: 28] [Article Influence: 1.6] [Reference Citation Analysis (0)] |
| 145. | Querejeta Roca G, Campbell P, Claggett B, Solomon SD, Shah AM. Right Atrial Function in Pulmonary Arterial Hypertension. Circ Cardiovasc Imaging. 2015;8:e003521; discussion e003521. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 64] [Cited by in RCA: 92] [Article Influence: 9.2] [Reference Citation Analysis (0)] |
| 146. | Egbe AC, Bonnichsen C, Reddy YNV, Anderson JH, Borlaug BA. Pathophysiologic and Prognostic Implications of Right Atrial Hypertension in Adults With Tetralogy of Fallot. J Am Heart Assoc. 2019;8:e014148. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 17] [Cited by in RCA: 25] [Article Influence: 3.6] [Reference Citation Analysis (0)] |
| 147. | Dernellis J. Right atrial function in hypertensive patients: effects of antihypertensive therapy. J Hum Hypertens. 2001;15:463-470. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 8] [Cited by in RCA: 10] [Article Influence: 0.4] [Reference Citation Analysis (0)] |
| 148. | Brochado L, Luz J, Fazendas P, Ferreira F, Grade J, Martinho M, Ferreira B, Cunha D, Baltazar O, Ilchyshyn N, Pereira H. Echocardiographic insights redefining risk in pulmonary arterial hypertension: a focus on right atrial volume index for enhanced stratification. Eur Heart J. 2024;45:ehae666.2173. [DOI] [Full Text] |
| 149. | Wessels JN, Mouratoglou SA, van Wezenbeek J, Handoko ML, Marcus JT, Meijboom LJ, Westerhof BE, Bogaard HJ, Strijkers GJ, Vonk Noordegraaf A, de Man FS. Right atrial function is associated with right venticular diastolic stiffness: RA-RV interaction in pulmonary arterial hypertension. Eur Respir J. 2022;59:2101454. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 2] [Cited by in RCA: 42] [Article Influence: 8.4] [Reference Citation Analysis (0)] |
| 150. | Wessels JN, van Wezenbeek J, de Rover J, Smal R, Llucià-Valldeperas A, Celant LR, Marcus JT, Meijboom LJ, Groeneveldt JA, Oosterveer FPT, Winkelman TA, Niessen HWM, Goumans MJ, Bogaard HJ, Vonk Noordegraaf A, Strijkers GJ, Handoko ML, Westerhof BE, de Man FS. Right Atrial Adaptation to Precapillary Pulmonary Hypertension: Pressure-Volume, Cardiomyocyte, and Histological Analysis. J Am Coll Cardiol. 2023;82:704-717. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 20] [Cited by in RCA: 36] [Article Influence: 12.0] [Reference Citation Analysis (0)] |
| 151. | Funaki R, Ogawa K, Mashitani Y, Oh T, Kashiwagi Y, Tanaka TD, Nagoshi T, Kawai M, Yoshimura M. The relationship between mixed venous blood oxygen saturation and pulmonary arterial and venous pressures in patients with heart failure. Physiol Rep. 2024;12:e70128. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 3] [Cited by in RCA: 3] [Article Influence: 1.5] [Reference Citation Analysis (0)] |
| 152. | Barker N, Fidock B, Balasubramanian N, W Macdonald A, Capener D, S Johns C, Karunasaagarar K, Fent G, Al-Mohammad A, Rothman A, G Kiely D, M Wild J, Swift A, Garg P. 27 Mixed venous oxygen levels in pulmonary hypertension is associated with right heart multi-parametric assessment. Heart. 2019;105 (Suppl 3):A1-A24. [DOI] [Full Text] |
| 153. | Sun Y, Wang L, Meng X, Gong S, Zhao Q, Shi L, Jiang R, He J, Wu W, Li Y, Luo C, Qiu H, Li J, Yuan P, Liu J. Soluble ST2 and mixed venous oxygen saturation for prediction of mortality in patients with pulmonary hypertension. J Thorac Dis. 2021;13:3478-3488. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 1] [Cited by in RCA: 3] [Article Influence: 0.6] [Reference Citation Analysis (0)] |
| 154. | Khirfan G, Almoushref A, Naal T, Abuhalimeh B, Dweik RA, Heresi GA, Tonelli AR. Mixed Venous Oxygen Saturation Is a Better Prognosticator Than Cardiac Index in Pulmonary Arterial Hypertension. Chest. 2020;158:2546-2555. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 5] [Cited by in RCA: 13] [Article Influence: 2.2] [Reference Citation Analysis (0)] |
| 155. | Levin ER, Gardner DG, Samson WK. Natriuretic peptides. N Engl J Med. 1998;339:321-328. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 1688] [Cited by in RCA: 1616] [Article Influence: 57.7] [Reference Citation Analysis (0)] |