OBJECTIVE:LIFECARD is a community-based longitudinal cohort in Pakistan investigating how anthropometric, environmental, and mental health factors (anxiety and depression) and lifestyle behaviors in low middle income country settings influence cardiovascular -kidney-metabolic (CKM) syndrome risk trajectories in individuals aged 10 to 45 years old. METHODS AND ANALYSIS:This 10-year longitudinal study will enroll approximately 4000 participants: 2000 adolescents (10-20 years) and 2000 young adults (21-45 years) from Karachi (peri-urban) and Matiari (rural) districts of Sindh. A multistage sampling design will be employed. Clusters of 200 households will be selected first in each area, followed by random selection of 75 households per cluster. One eligible participant per household will be enrolled to minimize clustering. Baseline assessments include sociodemographic data, clinical and family history, obstetric history (married women aged 15-45), tobacco/alcohol consumption, anxiety and depression screening, dietary intake, physical activity, and air quality measurements (personal, indoor, and outdoor). Anthropometric measurements and laboratory investigations (HbA1c, lipid profile) will be performed. These baseline variables will be captured every 2 years. Blood specimens will be bio-banked for future biomarkers and genomic analyses. Carotid intima-media thickness (cIMT) and plaque assessment via ultrasound will be conducted at baseline and every 5 years. CONCLUSION:LIFECARD will be Pakistan's first cohort investigating contextual risk factors for premature CKM from early adolescence (10 years) through adulthood (45 years). These insights will identify critical windows for early interventions to prevent disease initiation and progression.

Importance:Community health workers (CHWs) improve chronic disease management in underserved populations, but scalable integration strategies are limited. Objective:To evaluate whether a multidimensional intervention incorporating telementored CHWs and a structured participant-CHW-clinician feedback loop can improve diabetes outcomes. Design, Setting, and Participants:This 12-month randomized clinical trial was conducted at 3 institutionally and geographically diverse community clinics in Texas between September 1, 2023, and April 30, 2025, and included low-income, uninsured White Hispanic adults with type 2 diabetes identified through clinic databases. Data were analyzed between May 1 and July 31, 2025. Intervention:Individuals were randomized 1:1 to the intervention or control. For the intervention, CHWs delivered (1) group diabetes education, (2) individualized telehealth-based coaching, and (3) a novel participant-CHW-clinician feedback loop to facilitate communication, address participant concerns, and improve care coordination. The control was usual care (quarterly clinician visits and access to multidisciplinary and social services). Main Outcomes and Measures:The primary outcome was baseline to 12-month change in hemoglobin A1c (HbA1c) level. Secondary outcomes included changes in cholesterol levels, American Diabetes Association (ADA) guideline adherence, participant recruitment, intervention fidelity, and feedback loop issue resolution. Results:Of 257 participants included in the intention-to-treat analysis (mean [SD] age 54 [11] years; 166 [64.6%] female), 129 were in the intervention group and 128 were in the control group. The intervention reduced HbA1c (net difference, -1.0 [95% CI, -1.5 to -0.4] percentage points [pp]; P = .001), total cholesterol (net difference, -35.4 mg/dL; 95% CI, -54.6 to -17.2 mg/dL; P = .02), and low-density lipoprotein cholesterol (net difference, -29.7 mg/dL; 95% CI, -44.5 to -14.9 mg/dL; P < .001) levels compared with control. ADA guideline adherence improved for foot examinations (absolute risk [AR], 19.2 [95% CI, 7.4-30.9] pp; relative risk [RR], 1.65 [95% CI, 1.19-2.27]; P = .03) and urine microalbumin screening (AR, 15.8 [95% CI, 5.3-26.3] pp; RR, 1.24 [95% CI, 1.07-1.43]; P = .048). CHWs addressed 490 participant concerns (87.2%) via the feedback loop, including medication refills, glucose management, and access to care. Conclusions and Relevance:In this randomized clinical trial, the CHW intervention significantly improved diabetes outcomes in low-income settings, potentially by reducing fragmentation through structured feedback. Findings also highlight limitations in usual care, underscoring the need for scalable strategies to strengthen chronic disease management in low-income populations. Trial Registration:ClinicalTrials.gov Identifier: NCT04835493.

Cardiovascular disease (CVD) remains the leading cause of death worldwide. While advances in treatment have improved outcomes, the greatest gains in public health will come from primary prevention. Risk stratification is the foundation of CVD prevention. Traditional tools, such as pooled cohort equations (PCEs) and SCORE2, do not capture non-traditional risk factors and individual variability, driving efforts to refine existing approaches. We critically discuss emerging risk determinants for primary CVD prevention. Coronary artery calcium scoring can reclassify CVD risk but has limitations related to cost, access, and unvalidated improvements in clinical endpoints. Biomarkers such as apolipoprotein B and lipoprotein(a) may identify residual risk beyond LDL-C, particularly in patients with lipid discordance, but remain underused due to uncertain thresholds and the lack of prospective triallevel outcome data. Trials of colchicine in primary prevention have yielded mixed results, making the role of targeting inflammation unclear in CVD prevention. Polygenic risk scores can stratify genetic risk but face challenges in sensitivity, specificity, and generalizability. Multiomics approaches, while offering the promise of deeper phenotyping, lack established clinical applications and consensus on when their use is appropriate. Artificial intelligence may allow better prediction across cohorts but requires broader validation. Clonal hematopoiesis of indeterminate potential, a marker of inflammation and age-related CVD risk, lacks evidence supporting routine screening or intervention in younger, asymptomatic individuals. The proliferation of new risk stratification tools poses a key challenge: determining when additional data meaningfully alter clinical decisions. Until robust outcome-based evidence emerges, risk enhancers should guide, but not dictate, therapy in selected patients.

Cardiovascular diseases (CVDs) remain a leading cause of global morbidity and mortality, requiring precise risk prediction models for effective prevention and management. This review maps and evaluates globally utilized and country-specific CVD risk prediction models, including the Framingham Risk Score, Pooled Cohort Equations, PREVENT, WHO/ISH Risk Charts, INTERHEART, and SCORE2. A structured literature search was conducted using PubMed and Google Scholar, from which 30 relevant studies were selected. Most of the models integrate traditional risk factors such as age, sex, blood pressure, cholesterol, and smoking status to estimate CVD risk. While these models demonstrate moderate to good discrimination (C-statistics ranging from 0.66 to 0.80) and validation, their applicability varies across populations, with concerns about overestimation or underestimation in non-original cohorts. Notably, the WHO/ISH and Globorisk models address global diversity by incorporating regional calibrations, making them suitable for low- and middle-income countries. Similarly, the country-specific risk scores outperform global models due to their incorporation of local socio-demographics. Limitations persist across existing models, including the underrepresentation of younger individuals, ethnic minorities, and the exclusion of emerging risk factors. Future efforts must prioritize the development of locally validated, population-specific models to support equitable and effective CVD risk assessment and prevention.

AIMS:Elevated levels of lipoprotein(a) [Lp(a)] are increasingly recognized as an independent risk factor for cardiovascular diseases (CVDs). This systematic review and meta-analysis aimed to evaluate the impact of lipid apheresis therapy on serum Lp(a) levels in a wide array of disorders, particularly CVDs. METHODS AND RESULTS:Following PRISMA guidelines, we searched PubMed, Scopus, and Web of Science databases up to May 2025. Studies reporting pre- and post-treatment Lp(a) levels in participants undergoing lipid apheresis were included. A random-effects model was used when heterogeneity was significant. Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity. A total of 43 publications comprising 67 studies with 2466 participants were analysed. Lipid apheresis significantly reduced serum Lp(a) levels (SMD = -1.52; 95% CI = -1.76 to -1.29; P < 0.001). Subgroup analyses confirmed significant reductions across various methods of Lp(a) detection, disease backgrounds, and initial Lp(a) levels. One-session lipid apheresis studies (n = 6) also demonstrated a significant reduction (SMD = -1.51; 95% CI = -1.72 to -1.29; P < 0.001). Meta-regression suggested that publication year and disease background contributed to heterogeneity. CONCLUSION:Lipid apheresis is effective in significantly lowering serum Lp(a) concentrations across a range of patient groups and treatment modalities. These findings support the therapeutic role of lipid apheresis in managing elevated Lp(a).

BACKGROUND:Recent data report individuals with colorectal cancer (CRC) to be 2 to 4 times more likely to develop cardiovascular disease (CVD), while established CVD risk factors are linked with an elevated risk of CRC. This study aimed to evaluate national trends in combined CRC and CVD mortality in the United States and assess variations by demographic and geographic characteristics. METHODS:Combined mortality-related deaths in the United States were extracted using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). The Multiple Cause-of-Death Public Use record death certificates were studied to identify records in which both CRC and CVD were mentioned as either contributing or underlying causes of death on nationwide death certificates. RESULTS:Between 1999 and 2019, a total of 1,303,016 CRC-related deaths occurred in individuals aged ≥25 years, of which 394,871 (31.8%) deaths also noted CVD. The overall CRC+CVD-related age-adjusted mortality rate per 100 000 declined from 12.06 in 1999 to 6.69 in 2019. The age-adjusted mortality rates were higher in men (11.1) versus women (7.2). Among young adults aged 35 to 44 years, the crude mortality rates increased annually by 1.8% from 1999 to 2019. The age-adjusted mortality rates were highest for non-Hispanic Black or African American individuals and lowest for non-Hispanic Asian or Pacific Island people (12.22 versus 6.19). The rates were higher in nonmetropolitan (9.77) than metropolitan (8.58) counties and varied by region, being highest in the Northeast (10.6), followed by the West (9.0), Midwest (8.4), and South (7.9). CONCLUSIONS:Nearly one-third of CRC-related deaths also involved CVD. Although combined mortality has declined overall, it remains disproportionately high among men, Black or African American individuals, and rural populations. Notably, mortality is increasing among adults aged 35 to 44 years, highlighting persistent disparities and the urgent need for integrated cardiometabolic prevention strategies in patients with cancer.

To summarize key findings from cardiovascular disease prevention trials at the 2025 American Heart Association (AHA) Scientific Sessions. In a phase 2 trial, DR10624, a novel triple agonist, rapidly led to significant reductions in triglycerides and liver fat in patients with severe hypertriglyceridemia (sHTG). The CORE-TIMI 72a and CORE2-TIMI 72b trials showed that olezarsen markedly lowered triglycerides and reduced the risk of acute pancreatitis in patients with severe hypertriglyceridemia. The VESALIUS-CV trial demonstrated that evolocumab significantly lowered first major cardiovascular events in high-risk adults without prior myocardial infarction or stroke. The CORALreef Lipids trial found that the oral Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitor enlicitide reduced low-density lipoprotein cholesterol (LDL-C) by over 55

Background:Cardiovascular diseases (CVD) are the leading cause of mortality globally, with a disproportionate burden in low- and middle-income countries (LMIC). The workplace presents a strategic setting for preventive interventions targeting modifiable risk factors like physical inactivity, sedentary behavior, and poor diet among adults. This systematic review aimed to synthesize evidence on the effectiveness and implementation of workplace interventions targeting physical activity, sedentary behavior, or diet among employees in LMICs. Methods:We conducted a systematic review following PRISMA guidelines. Five databases (PubMed, Scopus, Cochrane CENTRAL, OATD, Google Scholar) were searched for studies published between January 2000 and May 2025. Eligible studies included working adults in LMIC workplaces, assessed interventions targeting at least one CVD-related behavior (physical activity, sedentary behavior, diet), and reported behavioral or cardiometabolic outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Given the heterogeneity in study designs, interventions, and outcomes, findings were synthesized narratively. Results:Sixteen studies (11 randomized controlled trials (RCTs)) from six countries (South Africa, Malaysia, Iran, India, Thailand, Mexico) were included. Interventions were heterogeneous: seven (43%) focused on physical activity (PA), five (31%) on reducing sitting time, four (25%) included dietary interventions, embedded within larger multicomponent programs.Technology-supported interventions (e.g., Stepathlon pedometer programme) increased step counts by +3,519 steps/day. Environmental interventions (sit-stand desks, text prompts) reduced sitting time by 6-66 minutes/day (largest effect: -66 min/day with frequent prompts). Multicomponent programmes that included dietary counselling or canteen modifications improved fruit and vegetable intake (27% to 64%) and reduced fat/calorie consumption (-553 ± 339 kcal). A standalone nutrition education programme also improved dietary knowledge and reduced sweet/snack intake.Multi-component, theory-informed programmes showed the most consistent improvements: systolic blood pressure reductions up to -10.2 mmHg, weight loss up to -1.8 kg, and total cholesterol reductions up to -0.45 mmol/L (≈17.4 mg/dL). Single-component environmental or technology-only interventions rarely improved biomarkers.Common implementation challenges included high attrition (15-30%) and declining digital engagement (app use fell from 77% to 31% by month 6). Overall risk of bias was moderate to high, driven by lack of blinding, reliance on self-reported outcomes (60% of studies), and attrition bias. Conclusion:Workplace interventions in LMICs show promise for improving CVD risk profiles, particularly multicomponent programs, although the number of studies remains limited. Simple modifications in physical activity, sedentary behavior and diet provide a feasible entry point but should be augmented with components designed to increase MVPA.

This review synthesizes current evidence on hypertensive disorders of pregnancy (HDP) and their impact on cardiovascular disease (CVD) in women, identifies gaps in healthcare provider knowledge, and proposes strategies to strengthen postpartum cardiovascular risk management. HDP, including gestational hypertension and preeclampsia, significantly increase early-onset and long-term CVD risk in women. Despite strong evidence, provider awareness and implementation of postpartum cardiovascular monitoring remain limited, especially in low-and middle-income countries. Substantial gaps in long-term risk counseling, HDP history documentation, and continuity of care beyond delivery persist. Emerging strategies such as task-shifting, mobile health interventions, integrated cardio-obstetric care teams, and context-specific care pathways offer promising solutions. Recognizing HDP as a sentinel event enables timely preventive care using a life-course approach. Strengthening provider education, integrating HDP history into electronic health records, and establishing structured postpartum screening programs are essential for reducing long-term cardiovascular morbidity and mortality in women.

Healthcare costs are ever increasing, with impacts across all socioeconomic backgrounds. As a result, financial strain and financial toxicity are a consequences of rising healthcare costs and economic variations, with significant negative impacts on cardiovascular disease. This review explores financial toxicity and the interplay of net worth, financial mobility, and social determinants of health in cardiovascular disease while also addressing the role of advocacy and policy in public health. Given the significant multidimensional aspects of financial toxicity, understanding its impact on cardiovascular disease is crucial to improving outcomes on a population-wide scale.

Current clinical practice guidelines for the primary prevention of cardiovascular disease recommend risk assessment to align the type and intensity of preventive efforts with an individual's risk. The 2025 American Heart Association/American College of Cardiology guideline for the prevention, detection, evaluation, and management of high blood pressure in adults and the 2026 American Heart Association/American College of Cardiology guideline on the management of dyslipidemia incorporate quantitative risk assessment, recommending the PREVENT (Predicting Risk of Cardiovascular Disease Events) equations to guide initiation and intensification of antihypertensive and lipid-lowering therapies, respectively. Given the growing awareness of the clustering of cardiovascular-kidney-metabolic risk factors along with the expanding armamentarium of cardioprotective therapies for obesity, diabetes, and chronic kidney disease, a harmonized approach that comprehensively assesses and addresses risk across these interconnected conditions is needed. The 2026 American Heart Association/American College of Cardiology guideline for the prevention, detection, evaluation, and management of cardiovascular-kidney-metabolic syndrome provides recommendations for the use of the PREVENT equations with outcome-specific risk thresholds for staging, detection of subclinical cardiovascular disease, and decision-making regarding initiation and intensification of cardiovascular-kidney-metabolic therapies. This approach integrates predicted risk (using PREVENT-CVD [cardiovascular disease], PREVENT-ASCVD [atherosclerotic cardiovascular disease], and PREVENT-HF [heart failure]) with the relative risk reduction expected from treatment for each outcome to estimate the expected benefit (ie, absolute risk reduction) from drug therapy. This scientific statement details the rationale for using outcome-specific PREVENT equations, the evidence base for selected risk thresholds, and the potential population-level impact of these recommendations. This scientific statement also offers practical guidance for applying risk assessment as the first step in shared decision-making and for addressing gaps in awareness, risk communication, and optimal implementation of evidence-based preventive therapies to improve outcomes in individuals with or at risk for cardiovascular-kidney-metabolic syndrome.

Marijuana, or cannabis, is the most commonly used illicit substance in the United States, with prevalence nearly doubling over the past decade. Accumulating evidence implicates cannabis use as a potentially modifiable risk factor for acute myocardial infarction, particularly among younger adults without traditional cardiovascular risk factors. Marijuana precipitates acute myocardial infarction through multiple converging mechanisms: increased myocardial oxygen demand via sympathetic activation, impaired oxygen delivery through carboxyhemoglobin elevation, coronary vasospasm, endothelial dysfunction, and a prothrombotic state characterized by enhanced platelet activation. Genetic variability in cannabinoid receptor expression and CYP2C9-mediated tetrahydrocannabinol metabolism further modulates individual susceptibility. Among patients with established coronary artery disease, population-based data suggest elevated cardiovascular risk with frequent use, though prospective cohort data remain conflicting. In post-percutaneous coronary intervention patients on dual antiplatelet therapy, cannabidiol inhibition of CYP2C19 may impair clopidogrel bioactivation, warranting consideration of alternative P2Y12 inhibitors. These findings highlight the importance of cannabis use screening in clinical practice and the need for prospective studies to guide evidence-based management.

AIM:The "2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome" retires, replaces, and expands upon the "2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults." The primary intended audience for this guideline is clinicians who care for patients across the spectrum of cardiovascular-kidney-metabolic syndrome, an interrelated condition characterized by the interconnections among metabolic risk factors (including obesity and type 2 diabetes), chronic kidney disease, and cardiovascular disease. METHODS:A comprehensive literature search was conducted from October 29, 2024, to April 14, 2025, to identify clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human subjects that were published since 2015 in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE:The focus of this clinical practice guideline is to create a living, working document that provides current knowledge in the field of cardiovascular-kidney-metabolic syndrome aimed at all practicing cardiologists, endocrinologists, nephrologists, and primary care and specialty clinicians who manage these patients.

South Asians (SAs) experience a disproportionately high burden of premature atherosclerotic cardiovascular disease, yet conventional risk assessment algorithms often underestimate their cardiovascular risk. This review highlights the evolving role of atherosclerosis imaging, namely, coronary artery calcium scoring and coronary computed tomographic angiography (CTA), as complementary tools for earlier detection and refined risk stratification in SAs. The authors review evidence demonstrating earlier appearance and greater coronary plaque burden in SAs, often accompanied by higher risk plaque features and inflammation, even in the setting of a zero or low coronary artery calcium score. Advances in coronary CTA, including artificial intelligence-enabled plaque quantification, perivascular fat attenuation index, and computed tomography-derived fractional flow reserve, enable the characterization of high-risk vascular biology and may guide targeted preventive therapies. Coronary artery calcium scoring can refine risk in SAs as broadly as in other ethnic groups. However, in younger SAs who may not yet have developed calcified plaque, the selective and judicious application of coronary CTA to visualize noncalcified plaque in targeted high-risk individuals offers an evolving strategy for earlier and personalized initiation of aggressive preventive therapies.

BACKGROUND:Atherosclerotic cardiovascular disease (ASCVD) poses a significant health challenge worldwide. While statins effectively reduce low-density lipoprotein (LDL) cholesterol and lower cardiovascular risk, patients with coronary artery disease who undergo revascularization remain vulnerable to recurrent ASCVD events. This study examined the link between statin intensity, LDL cholesterol levels, and recurrent ASCVD events in patients undergoing coronary interventions within a large health care system. METHODS:We conducted a retrospective analysis using the University of Pittsburgh Medical Center database, including patients aged ≥18 with coronary artery disease confirmed by revascularization (coronary artery bypass graft or percutaneous coronary intervention) since January 2010. Patients were categorized by statin intensity: guideline-directed statin intensity (GDSI), less than GDSI (<GDSI), or no statin therapy. Outcomes included recurrent myocardial infarction, ischemic stroke, and all-cause mortality over a median 6-year follow-up. RESULTS:Of 45 949 patients (69% men), 65% were on GDSI, 25% on <GDSI, and 10% were not on statins. GDSI patients compared with those on <GDSI or no statins had lower rates of myocardial infarction (21.6 versus 34.8 versus 65.3), myocardial infarction/revascularization (38.7 versus 57.5 versus 93.9), and ischemic stroke/transient ischemic attack (10.7 versus 17.7 versus 24.6) (P<0.001 for all). LDL cholesterol levels ≤70 mg/dL correlated with fewer adverse events, multivariable analysis indicated that GDSI significantly lowered recurrent ASCVD events and mortality. CONCLUSIONS:GDSI reduces recurrent ASCVD events and mortality more effectively than less intensive regimens or no statins. Optimizing statin use and LDL cholesterol monitoring could improve ASCVD management and outcomes.