Role of prognostic markers in the pathogenesis of hypertension

Table 2 Summary of pathogenesis of prognostic markers in patients with hypertension

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

BMI: Body mass index; BNP: B-type natriuretic peptide; CIMT: Carotid intima-media thickness; CRP: C-reactive protein; FPG: Fasting plasma glucose; GFR: Glomerular filtration rate; HDL: High-density lipoprotein; HF: Heart failure; hs-CRP: High-sensitivity C-reactive protein; IMT: Intima media thickness; LDL: Low-density lipoprotein; LV: Left ventricular; MAU: Microalbuminuria; UAE: Urine albumin excretion; NLR: Neutrophil-to-lymphocyte ratio; NT-proBNP: N-terminal pro-B-type natriuretic peptide; PAH: Pulmonary arterial hypertension; PAWP: Pulmonary artery wedge pressure; precPH: Precapillary pulmonary hypertension; PV: Pressure-volume; RA: Right atrial; RAP: Right atrial pressure; RAVI: Right atrial volume index; RV: Right ventricular; SBP: Systolic blood pressure; sPAP: Systolic pulmonary artery pressure; SvO₂: Mixed venous oxygen saturation; TC: Total cholesterol; TG: Triglycerides.