ObjectivesPrediction models based on traditional risk factors underestimate the risk for cardiovascular events (CVE) in SLE. We aimed to assess the occurrence of CVE in SLE patients according to their baseline subclinical atherosclerosis status.MethodsCarotid intima-media thickness at the carotid bulb level (CIMT) was prospectively assessed in consecutive SLE patients followed in our national reference center for rare diseases by a single evaluator, between February 2012 and February 2013. SLE patients with known CVE were excluded. CIMT >1.5 mm defined carotid plaque as a measure of subclinical atherosclerosis. The main outcome was a CVE defined as the occurrence during follow-up of myocardial infarction, ischemic stroke or symptomatic peripheral arterial disease.Results63 SLE patients (82.5% female, median age 39 [32-44.5]) were included. Among them, 24 (38.1%) had a carotid plaque >1.5 mm at baseline and 7 (11.1%) experienced a cardiovascular event during a median follow-up of 10.7 [8.2-11.0] years. All CVE occurred in the group of patients who had a carotid plaque at baseline. In the multivariable analysis, we observed that, after adjusting for the Framingham score and the body mass index, the presence of a carotid plaque was significantly associated with the occurrence of a cardiovascular event: odds ratio [95% confidence interval] = 17.2 ; 95 CI: [1.15-2499]; p = 0.039).ConclusionSubclinical atherosclerosis defined as a carotid plaque >1.5 mm is significantly associated with the clinical cardiovascular risk in SLE. Subclinical atherosclerosis should be regularly assessed in this population as part of the global cardiovascular risk evaluation.

Alterations in plasma levels of the components of the mineral metabolism (MM) system are related to cardiovascular diseases. However, gender differences of the whole MM system in patients with acute coronary syndrome (ACS) have not been reported. Our objective was to analyse the potential differences on the prognostic role of MM in women suffering an ACS as compared to men. We included 1,230 patients with ACS and collected clinical data and plasma levels of MM components. Primary outcome was a composite of acute ischaemic events, heart failure and all-cause mortality. Secondary outcomes included each component separately. 282 patients (22.9%) were female. After 5.44 years of follow-up, primary outcome occurred in 28.0% women and 23.5% men, and death in 10.6% and 9.4% respectively. FGF23 was associated with primary outcome in both sexes, and calcidiol only in men (HR 1.04, CI95%1.00-1.03). Klotho levels are inversely related to all-cause mortality only in women (HR 0.80, CI95% 0.67-0.96), while calcidiol (HR 0.84, CI95%0.72-0.98) and FGF23 levels (HR 1.02 CI95%1.00-1.03) were predictors in men, highlighting a possible gender-specific prognostic biomarker. These results underline the importance of considering MM biomarkers in risk stratification and management of patients with acute coronary syndromes, with attention to gender differences.

Inflammatory bowel disease (IBD) is a complex condition characterized by inflammation of the gastrointestinal system, encompassing Crohn's disease and ulcerative colitis. Patients diagnosed with IBD have an increased risk of atherosclerotic cardiovascular disease. This heightened risk can be attributed to a combination of mechanisms, including traditional risk factors, chronic inflammation, intestinal dysbiosis, increased risk of thrombosis, and the use of certain medications such as corticosteroids. There are significant gaps in current knowledge, particularly regarding the management of risk factors and the use of medications for cardiovascular disease prevention. Similarly, the cardiovascular effects of specific IBD therapies, particularly the newer ones, are not yet fully understood. This review focuses on the epidemiological evidence linking IBD with cardiovascular risk factors and cardiovascular disease. It describes the potential pathophysiological mechanisms underlying this association and examines the challenges involved in accurately assessing cardiovascular risk in these patients, including the utility of complementary tools such as subclinical atherosclerosis detection. Additionally, we consider the potential therapeutic implications for managing these patients. Finally, this review also underscores the importance of multidisciplinary collaboration. Effective teamwork among gastroenterologists, cardiologists, and general practitioners is essential for providing comprehensive care to patients with IBD.

Systemic lupus erythematosus (SLE) is associated with an elevated risk of atherosclerosis, with lupus nephritis (LN) representing a critical and potentially fatal target organ damage. This study aims to investigate the prevalence of LN in SLE patients, and its correlation with carotid atherosclerosis (CA).

A total of 151 SLE patients (age, 50.9 ± 14.6 years, 87.4% women) were included in the study. The 2024 KDIGO guideline was used to assess the LN prevalence, and carotid artery ultrasound was performed to identify plaque and intima-media thickness (IMT). The correlation between LN and CA in SLE patients was evaluated, and logistic regression analysis was conducted to identify CA risk factors.

A total of 47.0% of SLE patients exhibited LN, and the prevalence of CA was 37.7%. Patients with LN exhibited a higher carotid plaque ratio (47.9% vs 28.7%, p = 0.015) and IMT values [1.0(0.7, 1.1) mm vs. 0.8(0.7, 1.0) mm, p < 0.010] compared to those without LN. The presence of LN (p = 0.002), male sex (p = 0.039), age (p < 0.001), and serum TC (total cholesterol) (p = 0.016) were independent risk factors for SLE patients with CA. LN and related renal parameters demonstrated a strong association with CA in patients with SLE.

The prevalence of LN was significantly correlated with CA in SLE patients, indicating that early identification of LN in SLE patients has a high risk of CA, which may facilitate targeted prevention and reduce cardiovascular morbidity. Key Points • Lupus nephritis (LN) was present in 47.0% of systemic lupus erythematosus (SLE) patients, and carotid atherosclerosis (CA) was prevalent in 37.7% of the study. • Systemic lupus erythematosus (SLE) patients with lupus nephritis (LN) exhibited significantly higher carotid plaque ratios and increased intima-media thickness compared to those without LN. • The presence of lupus nephritis (LN), male sex, advanced age, and elevated total cholesterol levels was identified as independent risk factors for carotid atherosclerosis (CA) in patients with systemic lupus erythematosus (SLE).

Atherosclerosis, a chronic vascular disease, impacts various arterial systems, such as the coronary, carotid, cerebral, renal, and peripheral arteries. Dietary factors, especially alcohol consumption, significantly contribute to the progression of atherosclerosis. However, systematic evaluations of alcohol's impact on atherosclerosis are still limited. This study investigates the impact of alcohol consumption on atherosclerosis via meta-analysis and assesses the moderating effects of drinking frequency, gender, and other factors.

By December 2024, a comprehensive literature search was conducted across PubMed, Embase, Cochrane, and Web of Science databases. Studies evaluating the relationship between alcohol consumption and atherosclerosis were rigorously selected and assessed for quality. The study protocol was registered with the INPLASY database. Data extraction and statistical analysis were conducted using STATA 18.0 software. A total of 26 studies involving 326,513 patients across 10 countries were included. Considering that different biological mechanisms may regulate atherosclerosis in different arterial locations, we conducted subgroup analyses to explore differences in country, study type, arterial site, diagnostic criteria, type of alcohol, and gender.

The results show that the overall analysis did not show a significant promoting effect of alcohol consumption on the development of atherosclerosis (OR = 0.91, 95% CI 0.79-1.05). Subgroup analyses revealed several important trends. Alcohol consumption may increase the risk of atherosclerosis in specific countries (Japan, South Korea, Brazil, and Denmark), types of studies (cohort and case-control studies), arterial locations (coronary arteries), and diagnostic criteria (clinical diagnosis and computed tomography). Interestingly, we found that alcohol consumption may increase the risk of atherosclerosis in women. Furthermore, varying levels of alcohol consumption appear to result in differing risks of the disease.

The impact of alcohol consumption on atherosclerosis is not singular and may interact with multiple factors, including environmental factors, lesion location, and individual characteristics.

https://inplasy.com/inplasy-2025-1-0031/, INPLASY202510031.

Cardiovascular disease (CVD) is a leading cause of death in women with systemic lupus erythematosus (SLE) due to accelerated atherosclerosis that is not predicted by established CVD risk scores. This study aimed to develop, validate, and test a female-focused predictive atherosclerosis risk signature based on serum metabolites in patients with SLE.

Female patients with SLE were assessed for the presence (SLE-P; n=18) or absence (SLE-NP; n=26) of subclinical atherosclerosis using vascular ultrasound for carotid/femoral intima-media thickness. CVD risk was assessed using QRISK3 (which includes SLE diagnosis as a risk factor) and Framingham Risk Score. Serum metabolomics (n≥250) was performed and analyzed using machine learning pipelines. Despite having subclinical atherosclerosis, 44.8% to 100% of patients with SLE-P had low CVD risk according to QRISK3/Framlingham Risk Score scores. Using a lipid-focused metabolomic analysis, an improved atherosclerosis risk predictive signature was developed comprising 35 metabolites/5 clinical traits that classified patients with SLE-P and outperformed CVD risk assessment tools, lipid profiles measured in routine care, and clinical features alone. This "atherosclerosis risk signature" was validated in a second adult female SLE cohort (n=98) that predicted plaque status with moderate accuracy (area under the receiver operating characteristic curve, 0.79). The signature was then refined into a 5-feature subclinical plaque-predictive score that not only stratified the combined SLE-P/SLE-NP cohorts (n=142; area under the receiver operating characteristic curve, 0.84) but also predicted 3-year atherosclerosis progression in female postpubertal patients with juvenile-onset SLE (n=36; area under the receiver operating characteristic curve, 0.79). Finally, the 5-feature score identified distinct high and low subclinical atherosclerosis risk subgroups in a "real-world" setting of unscanned adult patients with SLE (n=38).

This atherosclerosis risk score could improve CVD risk assessment/management in female patients with SLE across age. Validation in non-SLE and healthy cohorts could further substantiate these findings.

Oxidative stress underlies many diabetic complications, including diabetic vasculopathy. It is unclear if oxidative stress has different effects in regionally distant arteries. We compared the contractile function of three arteries from diabetic mice and elucidated the mechanisms underlying their differential adaptation. We examined responses of the aorta, carotid and femoral arteries, isolated from the same diabetic (db/db) or normoglycemic control mice, to different vasoconstrictors in the presence and absence of indomethacin, apocynin, sulfaphenazole, L-NAME or a reactive oxygen species generating system to identify the enzyme(s) contributing to vascular dysfunction. Expression of superoxide dismutase (SOD) isoforms was measured. db/db aortae showed augmented contractile responses to KCl, phenylephrine, A23197 and U-46619 likely due to activated cyclooxygenases and hypersensitivity to thromboxane A2. Contractile responses of db/db carotid arteries were unaltered, likely due to higher SOD3 and SOD1 levels compared to the aortae. Femoral arteries were more vulnerable to oxidative stress, lacked SOD3 expression, and showed higher basal potassium channels activity. Phenylephrine contractions in femoral arteries were dependent on extracellular calcium entry; while contractions in aortae were dependent on extracellular calcium entry and intracellular calcium release. Femoral arteries from db/db mice exhibited higher basal potassium channels activity and attenuated contractility compared to control mice likely due to lower SOD levels. Heterogeneity exists between the three arteries at functional and molecular levels due to different signalling pathways and antioxidant defense mechanisms. Understanding regional differences in vasomotor control coupled with advanced delivery systems can help in developing therapies targeting specific vascular beds.

Elevated lipoprotein(a) [Lp(a)] is strongly associated with an increased risk of atherosclerotic cardiovascular disease; yet, large-scale studies on the epidemiology of elevated Lp(a) as well as its association with subclinical atherosclerosis in the Chinese population are limited.

This study aimed to estimate the prevalence of elevated Lp(a) in a large check-up population of China, and investigate its associations with both site-specific and multisite subclinical atherosclerosis.

Adults who underwent Lp(a) testing between 2017 and 2023 at Meinian health check-up centers in 30 provinces of China were included. Because the test results of Lp(a) were reported in either the mass unit (mg/dL) or the molar unit (nmol/L) and conversion between units was not recommended, separate analyses were conducted for each unit. Subclinical atherosclerosis was assessed using various imaging examinations at the carotid artery, the brain, and the coronary artery. The prevalence of elevated Lp(a) was estimated across the overall study population and various subpopulations. The logistic regression model was used to investigate the associations between elevated Lp(a) and subclinical atherosclerosis.

A total of 2,788,206 and 167,114 participants with the mass unit and the molar unit were included. In the mass unit group, the prevalence of Lp(a) >30 and >50 mg/dL was 18.67% and 8.41%, respectively. Significantly higher prevalence was observed among women, elderly individuals, and individuals with various cardio-renal-metabolic risk factors (all P < 0.05). Compared with Lp(a) ≤30 mg/dL, individuals with Lp(a) >30 to ∼50 mg/dL exhibited 11%, 15%, 9%, and 11% greater odds of increased carotid intima-media thickness, carotid plaque, subclinical brain infarcts, and coronary artery calcification, respectively. The odds were even higher for those with Lp(a) >50 mg/dL. Furthermore, elevated Lp(a) was significantly associated with the extent of coronary artery calcification, as well as subclinical atherosclerosis at 1, 2, and 3 sites, with the association being more pronounced in cases with severe extent and multisite involvement. These results were similar in the molar unit group.

A significant burden of elevated Lp(a) was found in China, highlighting the necessity of prioritized Lp(a) screening in high-risk groups. Elevated Lp(a) was identified as a significant risk factor for site-specific subclinical atherosclerosis, with stronger associations observed in severe extent and multisite involvement. Our findings suggest that individuals with elevated Lp(a) should undergo a comprehensive assessment of subclinical atherosclerosis at multiple sites to help prevent ASCVD.

Personalized healthcare is becoming increasingly popular given the vast heterogeneity in disease manifestation between individuals. Many commonly encountered diseases within cardiology are multifactorial in nature and disease progression and response is often variable due to environmental and genetic factors influencing disease states. This makes accurate early identification and primary prevention difficult in certain populations, especially young patients with limited Atherosclerotic Cardiovascular Disease (ASCVD) risk factors. Newer strategies, such as coronary artery calcium (CAC) scans and polygenic risk scores (PRS), are being implemented to aid in the detection of subclinical disease and heritable risk, respectively. Data surrounding CAC scans have shown promising results in their ability to detect subclinical atherosclerosis and predict the risk of future coronary events, especially at the extremes; however, predictive variability exists among different patient populations, limiting the test's specificity. Furthermore, relying only on CAC scores and ASCVD risk scores may fail to identify a large group of patients needing primary prevention who lack subclinical disease and traditional risk factors, but harbor genetic variabilities strongly associated with certain cardiovascular diseases. PRS can overcome these limitations. These scores can be measured in individuals as early as birth to identify genetic variants placing them at elevated risk for developing cardiovascular disease, irrespective of their current cardiovascular health status. By applying PRS alongside CAC scores, previously overlooked patient populations can be identified and begin primary prevention strategies early to achieve optimal outcomes. In this review, we expand on the current knowledge surrounding CAC scores and PRS and highlight the future possibilities of these technologies for preventive cardiology.

Atherosclerosis is the underlying disease in the entire spectrum of atherosclerotic vascular disease. Point of care ultrasound is a useful tool for its detection. Current guidelines recommend the use of scales such as SCORE 2 and SCORE 2OP in apparently healthy individuals and in those at intermediate-low risk, they recognize the role of the arterial plaque by ultrasound to refine risk stratification and the need for more aggressive preventive strategies. However, the way to evaluate the vascular territories in which there is presence of plaque, the amount or load of plaque is not homogeneous nor is it well protocolized. In this document, 2 protocols are proposed for the evaluation of vascular risk, VASUS and VASUS+, including the presence of ventricular hypertrophy with the objective of homogenizing clinical ultrasound in the assessment of vascular risk in clinical practice.

Hemodynamic shear stress, the frictional force exerted by blood flow on the endothelium, mediates vascular homeostasis. This review examines the biophysical nature and biochemical effects of shear stress on endothelial cells, with a particular focus on its impact on cardiovascular pathophysiology. Atherosclerosis develops preferentially at arterial branches and curvatures, where disturbed flow patterns are most prevalent. The review also highlights the range of shear stress across diverse human arteries and its temporal variations, including aging-related alterations. This review presents a summary of the critical mechanosensors and flow-sensitive effectors that respond to shear stress, along with the downstream cellular events that they regulate. The review evaluates experimental models for studying shear stress in vitro and in vivo, as well as their potential limitations. The review discusses strategies targeting shear stress, including pharmacological approaches, physiological means, surgical interventions, and gene therapies. Furthermore, the review addresses emerging perspectives in hemodynamic research, including single-cell sequencing, spatial omics, metabolomics, and multiomics technologies. By integrating the biophysical and biochemical aspects of shear stress, this review offers insights into the complex interplay between hemodynamics and endothelial homeostasis at the preclinical and clinical levels.

Black Americans suffer from disproportionately high rates of cardiovascular disease (CVD). Psychosocial stress contributes to this disparity. Previous studies reported that the Transcendental Meditation (TM) technique reduced CVD risk factors, surrogate endpoints, and clinical events in high-risk populations. However, no study has evaluated the effects of stress reduction with meditation on surrogate CVD markers such as carotid intima-media thickness (cIMT) along with CVD clinical events. Therefore, this randomized clinical trial evaluated the long-term effects of meditation and health education (HE) on cIMT and CVD events in high-risk Black adults.

Participants were Black women and men with CVD or at high risk who were randomized to either TM or HE. The primary outcome was a change in cIMT measured using B-mode ultrasound at baseline and 12 months. The main secondary outcome was major adverse cardiovascular events (MACE) at 5 years (maximum) of follow-up. Other secondary outcomes were MACE at 1 and 10 years of follow-up, blood pressure, and serum lipids after 1 year. Exploratory variables were a comparison of cIMT changes to historical controls and MACE after 14 years.

There were 197 randomized participants, of whom 136 completed posttest for cIMT. After 1 year, the TM and HE groups showed average cIMT changes of -0.0004 and -0.0003 mm, respectively, with no significant difference between the groups. Additionally, there were no significant differences between the groups in lipid levels or BP. However, both TM and HE groups showed prevention of progression of cIMT compared to historical controls at 12 months. In the survival analysis of MACE, there was a 65% relative risk reduction in the TM group after 5 (maximum) years of follow-up (HR = 0.346; 95% CI = 0.134-0.893; p = 0.017). At 1 and 10 years of follow-up, there were significant risk reductions in the TM vs. HE group, which was not significant at 14 years (all yearly maximums).

Both treatment groups demonstrated prevention of progression of cIMT over 12 months compared to historical controls. However, the TM group showed a relative risk reduction for MACE of 65% at 5 years. Therefore, as a lifestyle modification method, TM may be useful in the secondary prevention of CVD in this and possibly other high-risk groups.

ClinicalTrials.gov, NCT05642936.

Nonalcoholic fatty liver disease (NAFLD) with advanced liver fibrosis is associated with cardiovascular disease (CVD).

This work aimed to examine if markers of vascular injury mediate the link between liver fibrosis noninvasive tests (LFNITs) and CVD events, and to compare the incremental predictive value of LFNITs over established CVD risk scores.

Consecutively recruited individuals (n = 1692) with or without clinically overt coronary artery disease (CAD) from the Athens Cardiometabolic Cohort, were analyzed. Fibrosis-4 index (FIB-4), NAFLD Fibrosis score (NFS), and BARD score were evaluated for direct and indirect associations with indices of subclinical arterial injury including carotid maximal wall thickness (maxWT) and pulse wave velocity (PWV) and with a composite of major adverse cardiovascular events (MACE) that consisted of cardiac death, acute myocardial infarction, or coronary revascularization (39-month median follow-up).

FIB-4 was the only LFNIT that was consistently associated with multiple markers of vascular injury, irrespective of CAD presence and after controlling for traditional risk factors, surrogates of insulin resistance, or obesity (adjusted P < .05 for all). FIB-4 was also independently associated with CAD presence (adjusted odds ratio [OR] 6.55; 3.48-12.3; P < .001). Increased FIB-4 greater than 2.67 was incrementally associated with an increased risk for MACE (OR [95% CI] 2.00 [1.12-3.55], ΔAUC [95% CI] 0.014 [0.002-0.026]). These associations were mediated by maxWT rather than PWV. Only FIB-4 (>3.25) was independently and incrementally associated with all-cause mortality (adjusted P < 0.05).

In a cardiometabolically diverse population, the incremental associations of LFNITs with CVD outcomes were mediated by atherosclerotic burden rather than arterial stiffening. FIB-4 consistently demonstrated associations with all study end points. These findings provide mechanistic insights and support the clinical applicability of FIB-4 in CVD prevention.

Atherosclerosis is the underlying disease in the entire spectrum of atherosclerotic vascular disease. Point of care ultrasound is a useful tool for its detection. Current guidelines recommend the use of scales such as SCORE 2 and SCORE 2OP in apparently healthy individuals and in those at intermediate-low risk, they recognize the role of the arterial plaque by ultrasound to refine risk stratification and the need for more aggressive preventive strategies. However, the way to evaluate the vascular territories in which there is presence of plaque, the amount or load of plaque is not homogeneous nor is it well protocolized. In this document, 2 protocols are proposed for the evaluation of vascular risk, VASUS and VASUS+, including the presence of ventricular hypertrophy with the objective of homogenizing clinical ultrasound in the assessment of vascular risk in clinical practice.

Endothelial dysfunction is the main initiating factor in atherosclerosis. Through mechanotransduction, shear stress regulates endothelial cell function in both homeostatic and diseased states. Accumulating evidence reveals that epigenetic changes play critical roles in the etiology of cardiovascular diseases, including atherosclerosis. The metabolic regulation of epigenetics has emerged as an important factor in the control of gene expression in diseased states, but to the best of our knowledge, this connection remains largely unexplored in endothelial dysfunction and atherosclerosis. In this review, we (1) summarize how shear stress (or flow) regulates endothelial (dys)function; (2) explore the epigenetic alterations that occur in the endothelium in response to disturbed flow; (3) review endothelial cell metabolism under different shear stress conditions; and (4) suggest mechanisms which may link this altered metabolism to the regulation of the endothelial epigenome by modulations in metabolite availability. We believe that metabolic regulation plays an important role in endothelial epigenetic reprogramming and could pave the way for novel metabolism-based therapeutic strategies.

Subclinical atherosclerosis underlies most cardiovascular diseases, manifesting before clinical symptoms and representing a key focus for early prevention strategies. Recent advancements highlight the importance of early detection and management of subclinical atherosclerosis. This review underscores that traditional risk factor levels considered safe, such as low-density lipoprotein cholesterol (LDL-C) and glycated haemoglobin (HbA1c), may still permit the development of atherosclerosis, suggesting a need for stricter thresholds. Early-life interventions are crucial, leveraging the brain's neuroplasticity to establish lifelong healthy habits. Preventive strategies should include more aggressive management of LDL-C and HbA1c from youth and persist into old age, supported by public health policies that promote healthy environments. Emphasising early education on cardiovascular health can fundamentally shift the trajectory of cardiovascular disease prevention and optimise long-term health outcomes.

Groundbreaking strategies for preventive cardiology were showcased at the 2024 American Society for Preventive Cardiology (ASPC) Congress on Cardiovascular Disease (CVD) Prevention held in Salt Lake City, Utah, from August 2nd to 4th, 2024. The event featured 69 moderators and 13 scientific sessions comprised of 98 topics, 36 satellite events, 133 poster presentations, and 27 lifestyle classes. The conference highlighted innovative strategies focused on integrating cardiovascular, kidney, and metabolic health, presenting a cohesive approach for managing complex, interrelated conditions. Pivotal studies have addressed the role of lipid-lowering therapies, the benefits of early statin initiation, and the importance of precision medicine in preventing CVD. The ASPC's emphasis on translating this research into practical clinical tools has the potential to revolutionize preventive care strategies, making strides toward reducing the burden of CVD globally and improving long-term patient outcomes through personalized and early intervention approaches.

Identification of patients eligible for primary prevention statin therapy is complex, often relying upon risk algorithms that diverge internationally. Our goal was to develop a simpler global definition of statin-eligible primary prevention patients.

Randomized clinical trials (RCTs) cited in North American and European dyslipidemia guidelines justifying primary prevention statins for cardiovascular risk reduction were critically reappraised according to eligibility criteria and characteristics of actual enrollees. Statin-eligibility based on meeting minimal enrolment criteria versus risks calculated using either the Framingham Risk Score, the Pooled Cohort Equation and the Systematic Coronary Risk Estimate 2 were contrasted.

Patient scenarios meeting minimal RCT eligibility criteria seldom attained high enough 10 year risk of events according to the algorithms tested and thus would not be eligible for statin therapy. Overall, enrollees were 63.9 ± 8.9 years (mean ± SD) with low density lipoprotein-cholesterol (LDL-C) 3.53 ± 0.91 mmol/L. Enrollees in trials studying the lowest LDL-C levels were generally older and had additional risk factors.

Results of primary prevention RCTs justify treatment of more subjects and lower risk subjects than current risk algorithm-based guidelines. Based on a synthesis of RCT inclusion/exclusion criteria and the characteristics of enrollees, we propose that a statin-indicated primary prevention subject is one who is 40 to 70 years with a low density lipoprotein-cholesterol (LDL-C) ≥ 3.0 mmol/L or is 55 to 80 years with LDL-C ≥ 1.8 mmol/L and additional risk factors.

Background: During the 2024 annual meeting in London, The European Society of Cardiology released new guidelines (GLs) on chronic coronary syndromes (CCSs) and simultaneously published them in the European Heart Journal. Method: A few experts on the topic from Europe, South America, India, and Asia, who attended the presentation and the Question and Answer sections, met virtually to comment on the GLs after carefully reading the 123-page document. Result: There is a consensus that the presented GLs are a comprehensive, up-to-date, clear document of the available data on how to diagnose and treat CCSs and a definite step forward compared to all previous GLs. Of particular value are (a) the efforts to link both diagnosis and treatment to the underlying pathophysiology with the recognition that not all the ischaemic episodes are the same; (b) the decision to adopt the graphic of the so-called "Diamond Approach", although its spirit that no antianginal drug is superior to another is not fully adopted; and (c) the innovative way it condenses and expresses the relevant messages with eye-catching illustrations. Conclusions: The present article summarises and comments on the 123-page GLs, highlighting strengths and weaknesses according to the thoughts of the authors.

Haemostasis refers to the physiological process aimed at repairing vessel injury and preventing bleeding. It involves four interlinked stages culminating in the formation of a platelet-fibrin haemostatic plug that is eventually dissolved once the vessel heals. In contrast, arterial thrombosis is a pathological condition resulting from atheroma exposure, triggering the formation of a platelet-rich thrombus that may obstruct blood flow, leading to the clinical manifestations of ischaemic cardiovascular disease. The following review will provide a comprehensive overview of the finely regulated endogenous antithrombotic mechanisms responsible for maintaining the haemostatic balance and preventing intravascular thrombosis. Thereafter, it will further detail the different stages and mechanisms governing the intricate interplay between the vessel, platelets, and the coagulation cascade in haemostasis, highlighting the most recent advances in platelet biology and function, to further elucidate the differential traits and players contributing to pathological arterial thrombus growth. The review will also delve into the impact of emerging cardiovascular risk factors on tilting the haemostatic balance towards a pro-thrombotic state, thereby increasing the patient's vulnerability to thrombotic events. Finally, it will underscore the importance of early screening for subclinical atherosclerosis through advanced imaging technologies capable of quantifying plaque burden and metabolic activity since they may set the stage for an increased thrombotic risk. Implementing proactive interventions to halt atherosclerosis progression or inducing its regression at early stages is crucial for preserving haemostasis and reducing the likelihood of ischaemic atherothrombotic disease.

CD47 is an immune checkpoint widely regarded as a 'don't eat me' signal. CD47-based anti-cancer therapy has received considerable attention, with a significant number of clinical trials conducted. While anti-cancer therapies based on CD47 remain a focal point of interest among researchers, it is noteworthy that an increasing number of studies have found that CD47-based therapy ameliorated the pathological status of non-cancer diseases. This review aims to provide an overview of the recent progress in comprehending the role of CD47-based therapy in non-cancer diseases, including diseases of the circulatory system, nervous system, digestive system, and so on. Furthermore, we sought to delineate the promising mechanisms of CD47-based therapy in treating non-cancer diseases. Our findings suggest that CD47-based agents may exert their effect by regulating phagocytosis, regulating T cells, dendritic cells, and neutrophils, and regulating the secretion of cytokines and chemokines. Additionally, we put forward the orientation of further research to bring to light the potential of CD47 and its binding partners as a target in non-cancer diseases.

The first part of this review highlighted the evolving landscape of atherosclerosis, noting emerging cardiometabolic risk factors, the growing impact of exposomes, and social determinants of health. The prominent role of atherosclerosis in the bidirectional relationship between cardiovascular disease and cancer was also discussed. In this second part, we examine the complex interplay between multimorbid cardio-oncologic patients, cardiometabolic risk factors, and the harmful environments that lend a "syndemic" nature to these chronic diseases. We summarize management strategies targeting disordered cardiometabolic factors to mitigate cardiovascular disease and explore molecular mechanisms enabling more tailored therapies. Importantly, we emphasize the early interception of atherosclerosis through multifactorial interventions that detect subclinical signs (via biomarkers and imaging) to treat modifiable risk factors and prevent clinical events. A concerted preventive effort-referred to by some as a "preventome"-is essential to reduce the burden of atherosclerosis-driven chronic diseases, shifting from mere chronic disease management to the proactive promotion of "chronic health".

In patients with ischemic heart disease, coronary microvascular dysfunction is associated with cardiovascular risk factors and poor prognosis; however, data from healthy individuals are scarce.

The purpose of this study was to assess the impact of cardiovascular risk factors and subclinical atherosclerosis on coronary microvascular function in middle-aged asymptomatic individuals.

Myocardial perfusion was measured at rest and under stress using cardiac magnetic resonance in 453 individuals and used to generate myocardial blood flow (MBF) maps and calculate myocardial perfusion reserve (MPR). Subclinical atherosclerosis was assessed using 3-dimensional vascular ultrasound of the carotid and femoral arteries and coronary artery calcium scoring at baseline and at 3-year follow-up.

Median participant age was 52.6 years (range: 48.9-55.8 years), and 84.5% were male. After adjusting for age and sex, rest MBF was directly associated with the number of the metabolic syndrome components present (elevated waist circumference, systolic and diastolic blood pressure, fasting glucose, and triglycerides and low high-density lipoprotein cholesterol), insulin resistance (homeostatic model assessment for insulin resistance), and presence of diabetes. MPR was reduced in the presence of several metabolic syndrome components, elevated homeostatic model assessment for insulin resistance, and diabetes. Stress MBF was inversely associated with coronary artery calcium presence and with global plaque burden. Higher stress MBF and MPR were associated with less atherosclerosis progression (increase in plaque volume) at 3 years.

In asymptomatic middle-aged individuals free of known cardiovascular disease, the presence of cardiometabolic risk factors and systemic (poly-vascular) subclinical atherosclerosis are associated with impaired coronary microvascular function. Better coronary microvascular function reduces atherosclerosis progression at follow-up. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).

Noninsulin-based insulin resistance (IR) indices, simple and reliable surrogates for IR calculated without insulin level, have been reported to be associated with cardiovascular and cerebrovascular diseases.

Participants without diabetes from the cross-sectional baseline survey of the PRECISE (Poly-Vascular Evaluation for Cognitive Impairment and Vascular Events) cohort study were included in the present study. Noninsulin-based IR indices, including triglyceride-glucose (TyG) index, triglyceride glucose-body mass index (TyG-BMI) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, and metabolic score for insulin resistance (METS-IR) index, were calculated and stratified into quartiles. Intracranial, extracranial, coronary, subclavian, aorta, renal, ilio-femoral, and peripheral arteries were also assessed at baseline.

Of 2759 included participants, the average age was 60.9 (± 6.6) years, and 1460 (52.9%) were female. Compared with the first quartile of TyG index, the fourth quartile of TyG index was associated with an increased presence and extent of atherosclerotic plaques (OR, 3.51; 95% CI, 1.30-1.87; common odds ratio [cOR], 2.22; 95% CI, 1.76-2.79) and presence and extent of atherosclerotic stenosis (OR, 1.60; 95% CI, 1.24-2.06; cOR, 1.66; 95% CI, 1.30-2.12). Such associations were also observed for the relationship of TyG-BMI index, TG/HDL-C ratio, and METS-IR index with the presence and extent of atherosclerotic plaques and stenosis. Addition of 4 noninsulin-based IR indices to the basic model with traditional risk factors improved the predictive performance of the presence of atherosclerotic plaque and stenosis.

Elevated noninsulin-based IR indices levels were associated with an increased risk of presence and extent of atherosclerotic plaques and stenosis in non-diabetic, older individuals in the PRECISE study. Further, these IR surrogate markers have certain predictive performance to assess the risk of multiterritorial atherosclerosis.

Hypertension is responsible for more than two million deaths due to cardiovascular disease annually in Latin America (LATAM), of which one million occurs before 70 years of age. Hypertension is the main risk factor for cardiovascular morbidity and mortality, affecting between 20 and 40% of LATAM adults. Since the publication of the 2017 LASH hypertension guidelines, reports from different LATAM countries have confirmed the burden of hypertension on cardiovascular disease events and mortality in the region. Many studies in the region have reported and emphasized the dramatically insufficient blood pressure control. The extremely low rates of awareness, treatment, and control of hypertension, particularly in patients with metabolic disorders, is a recognized severe problem in LATAM. Earlier implementation of antihypertensive interventions and management of all cardiovascular risk factors is the recognized best strategy to improve the natural history of cardiovascular disease in LATAM. The 2024 LASH guidelines have been developed by a large group of experts from internal medicine, cardiology, nephrology, endocrinology, general medicine, geriatrics, pharmacology, and epidemiology of different countries of LATAM and Europe. A careful search for novel studies on hypertension and related diseases in LATAM, together with the new evidence that emerged since the 2017 LASH guidelines, support all statements and recommendations. This update aims to provide clear, concise, accessible, and useful recommendations for health professionals to improve awareness, treatment, and control of hypertension and associated cardiovascular risk factors in the region.

Embolic stroke of unidentified source (ESUS) represents 10-25% of all ischemic strokes. Our goal was to determine whether ESUS could be reclassified to cardioembolic (CE) or large-artery atherosclerosis (LAA) with machine learning (ML) using conventional clinical data.

We retrospectively collected conventional clinical features, including patient, imaging (MRI, CT/CTA), cardiac, and serum data from established cases of CE and LAA stroke, and factors with p < 0.2 in univariable analysis were used for creating a ML predictive tool. We then applied this tool to ESUS cases, with ≥ 75% likelihood serving as the threshold for reclassification to CE or LAA. In patients with longitudinal data, we evaluated future cardiovascular events.

191 ischemic stroke patients (80 CE, 61 LAA, 50 ESUS) were included. Seven and 6 predictors positively associated with CE and LAA etiology, respectively. The c-statistic for discrimination between CE and LAA was 0.88. The strongest predictors for CE were left atrial volume index (OR = 2.17 per 1 SD increase) and BNP (OR = 1.83 per 1 SD increase), while the number of non-calcified stenoses ≥ 30% upstream (OR = 0.34 per 1 SD increase) and not upstream (OR = 0.74 per 1 SD increase) from the infarct were for LAA. When applied to ESUS cases, the model reclassified 40% (20/50), with 11/50 reclassified to CE and 9/50 reclassified to LAA. In 21/50 ESUS with 30-day cardiac monitoring, 1/4 in CE and 3/16 equivocal reclassifications registered cardiac events, while 0/1 LAA reclassifications showed events.

ML tools built using standard ischemic stroke workup clinical biomarkers can potentially reclassify ESUS stroke patients into cardioembolic or atherosclerotic etiology categories.

Cognitive decline and dementia have been reportedly linked to atherosclerosis, the main cause of cardiovascular disease. Cohort studies identifying early brain alterations associated with subclinical atherosclerosis are warranted to understand the potential of prevention strategies before cerebral damage becomes symptomatic and irreversible.

The Progression of Early Subclinical Atherosclerosis (PESA) study is a longitudinal observational cohort study that recruited 4,184 asymptomatic middle-aged individuals (40-54 years) in 2010 in Madrid (Spain) to thoroughly characterize subclinical atherosclerosis development over time. In this framework, the PESA-Brain study has been designed to identify early structural, functional and vascular brain changes associated with midlife atherosclerosis and cardiovascular risk factors. The PESA-Brain study targets 1,000 participants at the 10-year follow-up PESA visit and consists of thorough neuropsychological testing, advanced multimodal neuroimaging, and quantification of blood-based neuropathological biomarkers.

We hypothesize that, in middle-age, the presence of cardiovascular risk factors and a high burden of subclinical atherosclerosis will be associated with structural, functional and vascular brain alterations, greater amyloid burden and subtle cognitive impairment. We further hypothesize that the link between subclinical atherosclerosis and poor brain health in midlife will be mediated by cerebrovascular pathology and intracranial atherosclerosis.

The PESA-Brain study started in October 2020 and is estimated to be completed by December 2024.

This study is in a unique position to unveil novel relationships between cardiovascular and brain alterations in the health-to-disease transition, which may have important implications for interventional and therapeutic approaches.

gov identifier: NCT01410318.

Women have a lower risk for cardiovascular (CV) disease compared to men. Whether this difference is influenced by the presence of hypertension-mediated organ damage is unknown.

To assess whether the presence of carotid plaque (CP) impacts the sex difference in risk for CV events in treated hypertensive patients.

From the Campania Salute Network Registry 2419 women and men <51 years of age with treated hypertension and free from prevalent CV disease were included. The presence of CP was identified by Doppler ultrasound (intima-media thickness≥1.5 mm). The primary outcome was a composite of fatal and non-fatal stroke or myocardial infarction, sudden death, TIA, myocardial revascularization, de novo angina, and atrial fibrillation.

Among patients without CP at baseline (n = 1807), women were older, with higher systolic blood pressure, serum cholesterol level and prevalence of LVH but lower serum triglycerides and eGFR, compared to men (all p < 0.001). Among patients with CP (n = 612), women were older, used higher number of antihypertensive drugs, had higher serum cholesterol level and prevalence of left ventricular hypertrophy (LVH), but had lower serum triglycerides and eGFR compared to men (all p < 0.001). During follow-up, women without CP had a lower risk for CV disease than men (hazard ratio, HR, 0.51, 95 % confidence intervals, CI, 0.27-0.99, p = 0.04) after accounting for cardiovascular risk factors, LVH, and antihypertensive treatment. In contrast, among patients with CP, women had similar risk for CV disease compared with men (HR 1.3, 95 % CI, 0.59-2.9, p = 0.48).

Our findings suggest that the presence of CP in young patients with treated hypertension offsets the CV disease protection in women.

NCT02211365.

Atherosclerotic cardiovascular disease, the leading cause of global mortality, is driven by lipid accumulation and plaque formation within arterial walls. Carotid plaques, detectable via ultrasound, are a well-established marker of subclinical atherosclerosis. In this study, we trained a deep learning model to detect plaques in 177,757 carotid ultrasound images from 19,499 UK Biobank (UKB) participants (aged 47-83 years) to assess the prevalence, risk factors, prognostic significance, and genetic architecture of carotid atherosclerosis in a large population-based cohort. The model demonstrated high performance metrics with accuracy, sensitivity, specificity, and positive predictive value of 89.3%, 89.5%, 89.2%, and 82.9%, respectively, identifying carotid plaques in 45% of the population. Plaque presence and count were significantly associated with future cardiovascular events over a median follow-up period of up to 7 years, leading to improved risk reclassification beyond established clinical prediction models. A genome-wide association study (GWAS) meta-analysis of carotid plaques (29,790 cases, 36,847 controls) uncovered two novel genomic loci (p < 5×10-8) with downstream analyses implicating lipoprotein(a) and interleukin-6 signaling, both targets of investigational drugs in advanced clinical development. Observational and Mendelian randomization analyses showed associations between smoking, low-density-lipoprotein (LDL) cholesterol, and high blood pressure and the odds of carotid plaque presence. Our study underscores the potential of carotid plaque assessment for improving cardiovascular risk prediction, provides novel insights into the genetic basis of subclinical atherosclerosis, and offers a valuable resource for advancing atherosclerosis research at the population scale.

Cardiovascular disease (CVD), particularly ischemic heart disease, remains the leading cause of death and morbidity in patients with type 1 diabetes. Detecting subclinical atherosclerosis could enhance cardiovascular risk stratification and enable individualised therapies. The aim of this study is to investigate the prevalence and predictors of subclinical atherosclerosis in patients with type 1 diabetes without overt cardiovascular disease (CVD) and to assess its impact on patient survival over a follow-up period of at least 5 years.

This observational study included 507 patients treated at the Diabetes Unit of the Hospital of Girona Doctor Josep Trueta between 2015 and 2023. The inclusion criteria for patients were as follows: those aged 18 and older with diabetes for a minimum of 10 years or those aged 40 and older with a diabetes for at least 5 years. Subclinical atherosclerosis was identified via ultrasound imaging of the carotid and femoral arteries. Clinical and biochemical evaluations were also conducted. Major cardiovascular events (MACE) and deaths from other causes were monitored, and survival analysis was performed using Kaplan‒Meier methods.

Subclinical atherosclerosis was detected in 218 patients (43%). Multivariate analysis revealed that the male sex, diabetic nephropathy, tobacco exposure, higher HbA1c levels, older age, and longer diabetes duration were significant predictors. During a mean follow-up of 70.64 ± 27.08 months, 19 patients experienced MACE, and 13 died from any cause. The probability of MACE or death was greater in patients with subclinical atherosclerosis, with a hazard ratio (HR) of 25.1 (95% CI 5.81-108, p < 0.001) for MACE and an odds ratio (OR) of 7.57 (95% CI 1.97-53.9, p = 0.004) for death.

Subclinical atherosclerosis is independently associated with increased overall mortality and MACE in patients with type 1 diabetes. Identifying clinical predictors can improve risk stratification and personalised therapeutic strategies to prevent MACEs in this high-risk population.

To investigate the distribution of arteriosclerotic vessels of arteriosclerosis, differential serum lipid profiles, and differences in the proportion of dyslipidaemia between patients with single-site arteriosclerosis and multi-site arteriosclerosis (significant hardening of ≥2 arteries).

The data of 6581 single-site arteriosclerosis patients and 5940 multi-site arteriosclerosis patients were extracted from the hospital medical record system. Serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) A1, ApoB concentrations and C-reactive protein (CRP) between patients with single-site arteriosclerosis and multi-site arteriosclerosis were collected and analyzed.

The most diseased arteries were coronary arteries (n=7099, 33.7%), limb arteries (n=6546, 31.1%), and carotid arteries (n=5279, 25.1%). TC, LDL-C, TC/HDL-C, and LDL-C/HDL-C levels were higher and CRP level was lower in multi-site arteriosclerosis patients than those in single-site arteriosclerosis patients. The TC, LDL-C levels in non-elderly (<65 years old) female patients were higher and TG/HDL-C, TC/HDL-C, LDL-C/HDL-C levels were lower than those in non-elderly male patients, while the TG, TC, LDL-C, and TG/HDL-C levels in elderly (≥65 years old) female patients were higher and LDL-C/HDL-C level was lower than those in elderly male patients. The proportion of dyslipidemia in descending order was as follows: low HDL-C (31.9%), elevated TG (16.9%), elevated TC (9.0%), and elevated LDL-C (4.2%). The levels of TC, LDL-C, TC/HDL-C, and LDL-C/HDL-C in patients with peripheral arteriosclerosis were higher than those in patients with cardio-cerebrovascular arteriosclerosis.

There were differences in serum lipid levels in patients with arteriosclerosis with different age, gender and distribution of arteriosclerotic vessels.

Atherosclerosis is a dynamic process. There is little evidence regarding whether quantification of atherosclerosis extent and progression, particularly in the carotid artery, in asymptomatic individuals predicts all-cause mortality.

This study sought to evaluate the independent predictive value (beyond cardiovascular risk factors) of subclinical atherosclerosis burden and progression and all-cause mortality.

A population of 5,716 asymptomatic U.S. adults (mean age 68.9 years, 56.7% female) enrolled between 2008 and 2009 in the BioImage (A Clinical Study of Burden of Atherosclerotic Disease in an At Risk Population) study underwent examination by vascular ultrasound to quantify carotid plaque burden (cPB) (the sum of right and left carotid plaque areas) and by computed tomography for coronary artery calcium (CAC). Follow-up carotid vascular ultrasound was performed on 732 participants a median of 8.9 years after the baseline exam. All participants were followed up for all-cause mortality, the primary outcome. Trend HRs are the per-tertile increase in each variable.

Over a median 12.4 years' follow-up, 901 (16%) participants died. After adjustment for cardiovascular risk factors and background medication, baseline cPB and CAC score were both significantly associated with all-cause mortality (fully adjusted trend HR: 1.23; 95% CI: 1.16-1.32; and HR: 1.15; 95% CI: 1.08-1.23), respectively (both P < 0.001), thus providing additional prognostic value. cPB performed better than CAC score. In participants with a second vascular ultrasound evaluation, median cPB progressed from 29.2 to 91.3 mm3. cPB progression was significantly associated with all-cause mortality after adjusting for cardiovascular risk factors and baseline cPB (HR: 1.03; 95% CI: 1.01-1.04 per absolute 10-mm3 change; P = 0.01).

Subclinical atherosclerosis burden (cPB and CAC) in asymptomatic individuals was independently associated with all-cause mortality. Moreover, atherosclerosis progression was independently associated with all-cause mortality.

Chronic inflammation in immune-mediated conditions has been associated with an increased risk in atherosclerotic disease. There is paucity of evidence regarding the prevalence of asymptomatic atherosclerosis in patients with ulcerative colitis (UC) and its association with disease activity. We sought to compare the prevalence of asymptomatic atherosclerotic disease between young patients with UC with and without mucosal healing (MH) and healthy control individuals.

An observational study was conducted in 2 hospitals in Buenos Aires, Argentina. Patients with UC 18 to 50 years of age with at least 1 previous colonoscopy in the last year were enrolled, along with age- and sex-matched healthy control individuals. Carotid and femoral ultrasound assessments were performed to determine the prevalence of atherosclerotic lesions and abnormal intima-media thickness (IMT). We compared the prevalence of atherosclerotic disease and the prevalence of abnormally increased IMT in at least 1 vascular territory.

Sixty patients with UC and 60 healthy control individuals were enrolled. Mean age was 38 years and 53.33% were men. Although the prevalence of atherosclerotic lesions was similar in patients with UC without MH when compared with both patients with UC with MH and control individuals (3.7% vs 0% vs 6.67%; P = .1), we found a significant increase in abnormal IMT in at least 1 vascular territory in UC patients without MH when compared with healthy control individuals (48.15% vs 26.67%; P = .05).

Patients with UC with active mucosal inflammation showed a significantly increased odds of asymptomatic femoral or carotid vascular disease when compared with control individuals.