Objective:Dyslipidemia has been linked to increased arterial stiffness. However, few studies have comprehensively assessed the cumulative effects of lipid profiles on arterial stiffness. Methods:Based on the initial recruitment of 7,134 participants from the China-PAR cohort, we finally included 6,717 participants with up to four repeated lipid measurements between baseline (1998-2008) and the most recent follow-up (2018-2020). Cumulative exposure to total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and remnant cholesterol (RC) was estimated using the area under the curve method. Arterial stiffness was measured in 2018-2020 using the arterial pressure-volume index (API) and the arterial velocity-pulse index (AVI), which reflect the stiffness of peripheral and central arteries, respectively. Results:Participants (mean age: 51.4 ± 10.3 years) included 2,598 men (38.68%), with a mean cumulative lipid exposure duration of 14.02 years. Cumulative TG, HDL-C, and RC were significantly associated with API levels, with adjusted β s (95% confidence intervals [ CIs]) of 2.31 (1.53, 3.08), -1.14 (-2.24, -0.04), and 2.39 (1.52, 3.25), respectively, for the highest quartile compared with the lowest quartile. Restricted cubic splines showed nonlinear associations of cumulative TG and RC with API and a linear association for HDL-C (all P < 0.05). For AVI, only cumulative HDL-C showed a significant inverse association, with an adjusted β (95% CI) of -1.16 (-2.12, -0.21) for the highest quartile, and a nonlinear association was observed ( P < 0.05). Conclusion:Long-term cumulative TG and RC were associated with increased peripheral arterial stiffness but not central arterial stiffness, and cumulative HDL-C was negatively associated with both peripheral and central arterial stiffness. These findings underscore the importance of long-term TG and RC control along with maintaining adequate HDL-C levels.

China has prioritized the prevention of cardiovascular disease. Over the past decade, significant investments have been made in public health services, along with the implementation of various health promotion policy agendas. As a result, environmental cardiovascular hazards have been substantially reduced, and care coverage within the primary health care system has improved. Nevertheless, adherence to various healthy lifestyles within the population has exhibited different secular trends, meanwhile the underutilization of secondary prevention medications among vulnerable populations is concerning. The Healthy China Initiative 2030 outlines a roadmap to prevent, pre-empt, and mitigate cardiovascular disease. China, along with other developing countries facing similar challenges, should consider fostering supportive social environments for healthy behaviors, targeting vulnerable groups for lifestyle adherence and access to care, expanding the scope of services provided by primary care providers, leveraging new technologies to develop scalable tools, and integrating surveillance systems for health promotion and care.

Arrhythmias such as atrial fibrillation and bradyarrhythmia impose a substantial public health burden. Although genetic predisposition contributes to arrhythmia risk, the extent to which modifiable lifestyle factors may mitigate this risk remains unclear. This study aimed to evaluate the association between a comprehensive healthy lifestyle and incident arrhythmias, and to assess whether these associations differ across levels of genetic susceptibility. A prospective cohort analysis was conducted using 341,736 UK Biobank participants after excluding individuals with baseline arrhythmias and incomplete lifestyle information. A healthy lifestyle score (HLS) incorporating smoking status, alcohol consumption, diet quality, and physical activity was constructed. Incident arrhythmias were identified through ICD-10 and procedure codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) for overall arrhythmia, atrial fibrillation, and bradyarrhythmia, adjusting for demographic and clinical covariates. Genetic susceptibility was quantified using a polygenic risk score (PRS) for atrial fibrillation, and joint lifestyle–genetic risk categories were used to evaluate their combined associations with AF risk. Over a mean follow-up of 10.9 years, 37,990 participants developed an incident arrhythmia, comprising 34,491 atrial fibrillation/flutter (AF) events and 9,399 bradyarrhythmia events; the composite count is a deduplicated union, so the two subtype counts overlap by 5,900 dual-subtype cases (Supplementary Table S4). Higher HLS values were associated with lower risks of overall arrhythmia and AF, whereas the association with bradyarrhythmia appeared weaker and non-monotonic. Compared with participants in the unfavorable lifestyle category, those in the favorable category had lower risks of AF (HR, 0.89; 95

Objective:Evidence suggests that depleted gut microbial α-diversity is associated with hypertension; however, whether metabolic markers affect this relationship remains unknown. We aimed to determine the potential metabolites mediating the associations of α-diversity with blood pressure (BP) and BP variability (BPV). Methods:Metagenomics and plasma targeted metabolomics were conducted on 523 Chinese participants from the MetaSalt study. The 24-hour, daytime, and nighttime BP and BPV were calculated based on ambulatory BP measurements. Linear mixed models were used to characterize the relationships between α-diversity (Shannon and Chao1 index) and BP indices. Mediation analyses were performed to assess the contribution of metabolites to the observed associations. The influence of key metabolites on hypertension was further evaluated in a prospective cohort of 2,169 participants. Results:Gut microbial richness (Chao1) was negatively associated with 24-hour systolic BP, daytime systolic BP, daytime diastolic BP, 24-hour systolic BPV, and nighttime systolic BPV ( P < 0.05). Moreover, 26 metabolites were strongly associated with richness (Bonferroni P < 0.05). Among them, four key metabolites (imidazole propionate, 2-hydroxy-3-methylbutyric acid, homovanillic acid, and hydrocinnamic acid) mediated the associations between richness and BP indices (proportions of mediating effects: 14.1%-67.4%). These key metabolites were also associated with hypertension in the prospective cohort. For example, each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of prevalent ( OR [95% CI] = 0.90 [0.82, 0.99]; P = 0.03) and incident hypertension ( HR [95% CI] = 0.83 [0.71, 0.96]; P = 0.01). Conclusion:Our results suggest that gut microbial richness correlates with lower BP and BPV, and that certain metabolites mediate these associations. These findings provide novel insights into the pathogenesis and prevention of hypertension.

AIMS:To evaluate the impact of long-term glycemic exposure and control status on cognitive function in older adults. MATERIALS AND METHODS:Using repeated measurements of fasting blood glucose (FBG) from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project, we calculated 10-year time-weighted cumulative fasting blood glucose (cumFBG) and glycemic variability, and identified FBG trajectories using group-based trajectory modelling among 26 108 participants. In addition, diabetic patients were categorized as consistently controlled or not according to long-term FBG levels. Mini-Mental State Examination was used to evaluate global and domain-specific cognition, and cognitive impairment was defined according to education-specific cutoffs. Linear and logistic regression models were applied to assess associations between FBG-related indicators and cognition. RESULTS:CumFBG was nonlinearly associated with global cognition and cognitive impairment (both P for nonlinearity < 0.05). Compared with participants with cumFBG < 900 mg/dL × year, those with cumFBG ≥ 1260 mg/dL × year had a 0.091-point lower z-standardized global cognitive score (95% CI: -0.142, -0.040) and a 3% increased cognitive impairment risk (OR: 1.030; 95% CI: 1.010, 1.050). Among specific domains, attention appeared more susceptible, with declines emerging when cumFBG ≥ 900 mg/dL × year. Notably, among individuals with cumFBG ≥ 1260 mg/dL × year, increasing trajectory had a 21.2% increased cognitive impairment risk (OR: 1.212; 95% CI: 1.122, 1.310). Higher variability was associated with worse cognition. Furthermore, only diabetic participants with consistent control exhibited cognition comparable to those without diabetes. CONCLUSION:Elevated cumFBG, especially in an increasing pattern, influenced cognition in older adults and sustained glycemic control appeared to mitigate these adverse impacts.

Objective:To examine the associations of sleep duration and physical activity (PA) with central obesity among Chinese adults. Methods:Based on the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project, 175,373 observations from 106,518 participants were included. Generalized estimating equations quantified the associations of sleep duration and PA with waist circumference (WC) and central obesity. Stratified and joint analyses were performed to evaluate combined effects, and an isotemporal substitution model was used to assess substitution effects. Results:Suboptimal sleep duration (< 7 h/day or ≥ 9 h/day) and inadequate PA were associated with higher WC and an increased risk of central obesity. Compared with optimal sleep duration (7 - < 9 h/day), both longer (≥ 9 h/day) and shorter (< 7 h/day) sleep durations were associated with increased WC (0.27 cm [95% confidence interval ( CI): 0.18, 0.35] and 0.15 cm [95% CI: 0.04, 0.27], respectively) and a higher risk of central obesity (odds ratio, 1.09 [95% CI: 1.07, 1.12] and 1.05 [95% CI: 1.02, 1.08], respectively). Joint analyses revealed that individuals with inadequate PA and short sleep duration had the highest WC and highest risk of central obesity. Among individuals sleeping > 8 h/day, substituting 30 min/day of sleep with moderate-to-vigorous PA significantly reduced the risk of central obesity. Conclusion:Suboptimal sleep duration has a detrimental effect on central obesity, and adequate PA can mitigate this effect. The impact of reallocating sleep duration varies by sleep duration, highlighting the need to optimize both PA and sleep patterns in China.

BACKGROUND:In China, the associations between long-term fine particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5) exposure and coronary heart disease appear to differ from those reported in high-income countries, thus potentially reflecting differences in PM2.5 composition. However, constituent-specific evidence from national cohort studies remains limited. OBJECTIVES:This study aimed to investigate the associations of long-term exposure to PM2.5 constituents with the incidence and mortality risks of coronary heart disease and its subtype, acute myocardial infarction (AMI). METHODS:This nationwide prospective cohort study was conducted in 101,906 adults from the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) Project who were free of cardiovascular disease at baseline. Participants were followed up from 2003 to 2019. Annual residential exposures to PM2.5 constituents, including elemental carbon (EC), organic carbon (OC), nitrate, and sulfate, were estimated using validated satellite-based machine learning models. Cox proportional hazards models with time-varying exposures were used to estimate HRs and 95% CIs per IQR increase, adjusted for major demographic, behavioral, and clinical covariates. RESULTS:During a median follow-up of 11.08 years (1,230,732 person-years), 3,500 incident cases of coronary heart disease, including 1,771 AMI events, and 1,321 coronary heart disease deaths, including 808 AMI deaths, were recorded. Per IQR increase in EC, OC, nitrate, and sulfate exposure, HRs for coronary heart disease incidence were 1.10 (95% CI: 1.01-1.19), 1.60 (95% CI: 1.31-1.95), 1.43 (95% CI: 1.06-1.95), and 0.93 (95% CI: 0.82-1.06), respectively. Similar positive associations for EC, OC, and nitrate were observed for coronary heart disease mortality and AMI outcomes, whereas the health impacts of sulfate were weaker and less consistent across outcomes. Concentration-response curves indicated an overall increasing coronary heart disease risk for OC, EC, and nitrate exposure with a plateau or slight attenuation in the higher exposure range of EC and OC, whereas sulfate exposure showed nonlinear associations without a sustained increase in risk. CONCLUSIONS:Long-term exposure to specific PM2.5 constituents was associated with increased risks of coronary heart disease and AMI, thus highlighting the need for constituent-specific air pollution control beyond PM2.5 mass.

Regular physical activity (PA) has been demonstrated as one of the simplest ways to reduce the risk of incident cardiovascular disease (CVD). The specific impacts of different types of PA on cardiovascular health are, however, not yet to be well understood. In this review, we systematically outline the definitions and current guideline-recommendations for different types of PA, and summarize the effects of three main types, including aerobic, muscle-strengthening, and combined aerobic and muscle-strengthening PA, on CVD and its risk factors. Additionally, this review also summarizes the potential mechanisms through which they promote cardiovascular health. By integrating current research findings, this review provides insights into the general beneficial effects of appropriate PA types, highlights the potential application of combined PA in the prevention of CVD, and offers insights for developing tailored PA recommendations to maximize CVD prevention efficacy.

Circulating sphingolipids, composed of a sphingoid backbone, a fatty acid chain, and a polar head group, exert important physiological effects and are dysregulated in various metabolic disorders. Ceramides and sphingomyelins (SM) may contribute to elevated cardiovascular risk via pathways that are independent of traditional lipid metabolism, playing an important role in identifying residual risk. However, the impacts of specific types of ceramides and sphingomyelins on cardiovascular outcomes remain uncertain. In this review, we (i) summarize the latest advances in prospective evidence linking circulating ceramides and sphingomyelins to cardiovascular diseases (CVD), (ii) discuss improvements in predicting adverse cardiovascular outcomes using comprehensive risk scores based on ceramides, and (iii) further illustrate potential modifiable factors influencing ceramides and sphingomyelins levels, such as diet, physical activity, and air pollutants. In conclusion, circulating ceramides and sphingomyelins are valuable cardiovascular risk biomarkers, serving as key factors in both primary and secondary prevention by identifying the additional risk of CVD independent of conventional lipid biomarkers, with distinct roles among different types of ceramides and sphingomyelins. Further studies are urgently needed to elucidate the causal relationships between specific types of circulating ceramides or sphingomyelins and subtypes of CVD and their underlying biological mechanisms. To advance the practical application of ceramides and other sphingolipids in the prevention and treatment of CVD, large-scale studies are required to determine the extent to which modifiable factors reduce cardiovascular risk by regulating ceramide and sphingomyelin levels, and continued efforts should be focused on targeted interventions and clinical translation in sphingolipid metabolism.

Vascular smooth muscle cell (VSMC) migration is the key event in the pathogenesis of atherosclerosis (AS) and plaque instability. Trimethylamine-N-oxide (TMAO) induces VSMC migration to promote the progression of AS. However, the effects of the N6-methyladenosine (m6A) modification on this process remain unclear. Here, TMAO increased total m6A levels in human aortic smooth muscle cells (HASMCs) and decreased fat mass and obesity-associated protein (FTO) and YTH domain-containing family protein 2 (YTHDF2) protein expression. FTO or YTHDF2 overexpression significantly inhibited HASMC migration induced by TMAO. Mechanistically, the COL3A1 gene was shown to be critical for the regulation of HASMC migration by FTO or YTHDF2. Furthermore, methylated RNA immunoprecipitation and RNA stability assays demonstrated that FTO bound to the COL3A1 mRNA and altered its m6A modification, resulting in its decay. In vivo, VSMC-specific FTO or YTHDF2 deletion aggravated AS and plaque instability, whereas adeno-associated virus serotype 9 (AAV9)-mediated VSMC-specific YTHDF2 overexpression or COL3A1 knockdown exerted protective effects on AS and/or plaque instability. Notably, VSMC-specific FTO deletion promoted VSMC migration in atherosclerotic lesions in ApoE−/− AS model mice, whereas VSMC-specific YTHDF2 overexpression had the opposite effect. Overall, the in vitro and in vivo evidence highlights the critical role of the FTO/YTHDF2/COL3A1 axis in VSMC migration, AS, and plaque instability, suggesting that targeting the FTO/YTHDF2/COL3A1 axis in VSMCs may be a novel and promising therapeutic strategy for the treatment and prevention of AS and plaque instability.

BACKGROUND:Existing studies focused on the association of lipid trajectory classifications with cardiovascular outcomes, whereas the natural life-course pattern and sex-specific modulation by obesity are poorly characterized. OBJECTIVES:This study sought to characterize the sex-specific lipid trajectories and examine the role of obesity indicators in shaping them. METHODS:In a longitudinal cohort of 83,487 Chinese adults (median follow-up: 11.00 years; Q1-Q3:6.80-11.72) with 2-4 repeated lipid measurements, we applied generalized additive mixed model to characterize age-related lipid trajectories and assess modifications by obesity indicators (body mass index and waist circumference). RESULTS:Total cholesterol (TC), low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol (non-HDL-C) exhibited 3-phase trajectory (increase, plateau, slight decrease), whereas triglyceride and remnant cholesterol showed 2-phase (increase, decrease). Female subjects showed delayed trajectory transitions (13-17 years) and more adverse late-adulthood lipid profiles than male subjects did. Obesity indicators were positively associated with elevated lipid levels (all P < 0.001), with stronger association in male subjects than in female subjects (eg, per 1-SD body mass index increase, β-coefficient for TC: 3.43 [95% CI: 3.15-3.71] vs 2.71 [95% CI: 2.48-2.94] mg/dL, respectively; Pinteraction < 0.001). Notably, the lipid-lowering associations of adiposity reduction attenuated with age in male subjects, whereas in female subjects they remained stable for triglyceride and remnant cholesterol (eg, the mean differences between obese and non-obese groups defined by waist circumference 28.96 [95% CI: 23.13-32.14] and 3.19 [95% CI: 2.72-3.66] mg/dL) or showed "L-shape" pattern with inflection around age 40 for TC, low-density lipoprotein cholesterol, and non-HDL-C. CONCLUSIONS:Our findings highlight sex-specific impact of obesity on lifelong lipid trajectories, suggesting sex- and age-specific strategies for early lipid management and obesity intervention.

ABSTRACT Background To analyze the interplay between family history of type 2 diabetes (T2D) and cardiovascular health (CVH) in relation to T2D onset age and subsequent cardiovascular disease (CVD) risk. Methods A total of 79 831 participants were included to investigate the association between family history and T2D onset age. Then, 7387 diagnosed T2D patients were 1:1 matched with non‐T2D individuals to analyze the association of T2D onset age with subsequent CVD risk. The benefit of good CVH was further assessed. Stratified Cox regression and conditional Cox regression were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Family history was associated with younger T2D onset, with an approximately 2.4‐year earlier onset of T2D, which further increased the subsequent risk of CVD. Compared with individuals without family history, those with family history had HRs (95% CIs) of 3.911 (3.041, 5.032), 3.785 (3.385, 4.233), 3.627 (3.340, 3.938), 3.465 (3.189, 3.764), and 3.169 (2.787, 3.603) for T2D onset at < 40, 40–50, 50–60, 60–70, and ≥ 70 years old, respectively (Pinteraction = 0.007). Among individuals with family history, HR (95% CI) for incident CVD was 3.598 (1.372, 9.433) for those diagnosed T2D < 50 years compared with those without T2D, while the HR (95% CI) was 2.336 (1.232, 4.428) among those without family history. However, high CVH could mitigate risk of young‐onset T2D, and could further decrease CVD risk after their T2D diagnosis. Conclusions Having family history of T2D increased susceptibility to young‐onset T2D and subsequent CVD risks, while ideal CVH could counteract these risks, highlighting the necessity of early screening and intervention.

Background Evidence on the association between family history and atherosclerotic cardiovascular disease (ASCVD) across age groups remains limited. Objectives This study aimed to evaluate the relations of family history of ASCVD (FHA) with incident ASCVD and its predictive value across age groups in China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) and UK Biobank. Methods A total of 117,640 Chinese and 457,781 UK adults were included from 2 population-based cohorts, with family history assured by face-to-face interviews with standardized questionnaires. Results During median follow-ups of 6.0 (Q1-Q3: 5.7-11.4) years (China-PAR) and 11.8 (Q1-Q3: 11.0-12.5) years (UK Biobank), 4,681 and 26,913 ASCVD cases occurred. Generally, FHA was consistently associated with higher ASCVD risk, but the association weakened with age (Pinteraction < 0.001). The strongest effect was in adults <45 years, with HRs of 1.48 (95% CI: 1.11-1.96) in China-PAR and 1.47 (95% CI: 1.23-1.76) in UK Biobank, which was transformed to 6.75 and 5.33 years ASCVD-free years lost at the index of 20 years, and this gap decreased to 3.40 and 1.42 years at the index of 80 years, respectively. Notably, sibling history conferred greater risk than parental history (Pheterogeneity < 0.001). Conclusions In both populations, FHA is a key indicator for identifying high ASCVD risk, especially in younger individuals, with a stronger impact driven by sibling history. These findings highlight the importance of tailoring recommendations for identifying high-risk individuals based on family history, with consideration of different age groups.

BACKGROUND:Natto Red Yeast Rice (NRYR) is a dietary supplement used to lower blood lipid. However, evidence on its effects on regulating lipid levels is limited. OBJECTIVES:The aim of this study was to assess whether NRYR can lower low-density lipoprotein cholesterol (LDL-C) levels and regulate other lipids, both alone and in addition to simvastatin. METHODS:We enrolled 1,110 participants who were randomized into 4 groups to receive a 3-month intervention of placebo, NRYR (1,950 mg/d), simvastatin (20 mg/d), or NRYR (1,950 mg/d) plus simvastatin (20 mg/d). The primary outcome was the change in LDL-C levels after 3 months, which were evaluated using linear mixed models. The primary analyses were conducted according to the modified intention-to-treat principle. Safety outcomes were also recorded. RESULTS:Significant reductions in LDL-C levels were observed in the NRYR, simvastatin, and combination group. The differences in the absolute/percent change in LDL-C levels from baseline to 3 months were -21.02 mg/dL (95% CI: -27.98 to -14.06 mg/dL)/-13.21% (95% CI: -17.88% to -8.54%), -25.80 mg/dL (95% CI: -32.64 to -18.97 mg/dL)/-17.08% (95% CI: -21.67% to -12.50%), and -32.74 mg/dL (95% CI: -39.74 to -25.73 mg/dL)/-21.22% (95% CI: -25.92% to -16.52%), respectively, compared with placebo (all P < 0.001). Compared with simvastatin alone, adding NRYR demonstrated a significant decrease in LDL-C levels with a net absolute/percent change of -7.95 mg/dL (95% CI: -13.79 to -2.11 mg/dL; P = 0.008)/-5.05% (95% CI: -8.87% to -1.24%; P = 0.009) at 1 month, but the effect was not significant at 3 months. Adverse event rates were similar across the 4 groups. CONCLUSIONS:NRYR alone lowered LDL-C levels, and its combination with simvastatin was associated with numerically but not significantly lower LDL-C levels than using simvastatin alone. (ChiCTR2200064214, ChiCTR2200064215).

It is still unclear how the risk of cardiovascular disease (CVD) changes across life course and the specific influence of body mass index (BMI) on risk trajectory. We included 106,962 participants aged 35–74 from a Chinese longitudinal cohort during 1992 to 2021 with 4 repeated measurements. China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) equation was applied to calculate 10-year CVD risk. General additional mixed model and Joinpoint model were used to elaborate CVD risk trajectory and the potential benefits of normal BMI. The 10-year CVD risk for Chinese adults increased from 1.11

AIMS:To develop a cardiovascular disease (CVD) risk prediction model with improved accuracy and interpretability by integrating diverse risk factors and applying Automated Machine Learning (AutoML), thereby enhancing clinical utility over conventional models. METHODS:This is a prospective cohort study. Data were obtained from the Multi-Ethnic Study of Atherosclerosis (MESA), including baseline and fifth follow-up visits, comprising 4713 participants. Exercise and dietary data were harmonized via Metabolic Equivalent of Task (MET) and Healthy Eating Index-2015 (HEI-2015), respectively. Predictor selection was performed using the Boruta algorithm alongside Random Forest (RF) error rate cross-validation. Logistic regression, four traditional machine learning algorithms, and H2O AutoML were each applied for model training and evaluation. Finally, the best-performing model was further interpreted using SHapley Additive exPlanations (SHAP). RESULTS:A total of 21 predictors were selected, including age, sex, and Total Cholesterol (TC). Among the evaluated models, H2O AutoML outperformed other methods with an accuracy of 0.864, specificity of 0.892, precision of 0.610, F1 score of 0.670, and a Youden index of 0.635, achieving the highest AUC of 0.882 (0.846-0.918). SHAP analysis revealed the relative importance of predictors, with age, TC and Digit Symbol Score (DSS) ranking highest. CONCLUSIONS:This study developed an AutoML-based CVD risk prediction model with superior discrimination and calibration, providing clinicians a practical tool for risk stratification. By enabling personalized prevention and early identification of high-risk individuals, this model has the potential to reduce CVD burden at the population level. Notably, DSS exhibited high importance and may represent a candidate risk marker.

Patients undergoing percutaneous coronary intervention (PCI) remain at substantial residual inflammatory risk, potentially driven by clonal hematopoiesis of indeterminate potential (CHIP), a novel pro-inflammatory contributor to atherogenesis. However, the clinical implications of CHIP-inflammation interplay in secondary prevention remain insufficiently understood. We aimed to investigate the joint impact of CHIP and systemic inflammation on prognosis among PCI patients. This cohort included PCI patients receiving guideline-directed lipid-lowering and dual antiplatelet therapies. CHIP mutations were identified by targeted sequencing with a mean sequencing depth of 985 × . Systemic inflammation was assessed using 12 routine inflammatory indices. Cox proportional hazards models were used to assess the impact of CHIP and inflammatory indices on 5-year all-cause mortality, the primary outcome. Major adverse cardiac and cerebrovascular events (MACCE) comprised all-cause mortality, nonfatal myocardial infarction, ischemic stroke, stent thrombosis, and unplanned revascularization. Among 3640 PCI patients, 799 (21.95

Genetic predisposition contributes substantially to the risk for atherosclerotic cardiovascular disease (ASCVD). Polygenic risk scores (PRS), which quantify this inherited susceptibility, have demonstrated strong predictive performance in European populations, with accumulating evidence supporting their use in clinical practice. However, East Asian populations face a notable gap in PRS development and validation, with limited studies guiding their clinical application. In this state-of-the-art review, the authors summarize current evidence on PRS for coronary artery disease and ischemic stroke, the 2 major subtypes of ASCVD, in East Asian populations. The authors place specific focus on cross-ancestry integration strategies and key methodological considerations to enhance predictive accuracy. Additionally, the authors highlight the clinical utility of ASCVD PRS in primary and secondary prevention and their evaluation in real-world settings and outline strategies for clinical translation into routine care for East Asians. This review underscores the need for initiatives to facilitate the application of PRS across diverse populations.