Cardiovascular disease (CVD) remains the leading global cause of morbidity and mortality. While low-dose aspirin is well established for secondary prevention, its role in primary prevention is controversial because modest benefits in cardiovascular benefits must be balanced against increased bleeding risk, as highlighted by recent large trials. Current guidelines recommend restricting aspirin use to individuals at higher cardiovascular risk without elevated bleeding risk, yet significant heterogeneity persists in defining these thresholds. Evidence from randomized trials, guidelines, cohort and modeling analyses, and post hoc or observational subgroup studies suggests that selected patients with advanced subclinical atherosclerosis or specific high-risk markers may have a more favorable risk–benefit profile, although the certainty and directness of evidence vary across subgroups. This narrative review and pragmatic clinical guide presents an illustrative tiered framework based on clinical, imaging, and biomarker markers—such as coronary artery calcium score, carotid plaque score, and lipoprotein(a)—to support individualized discussion of preventive aspirin therapy. The framework is not a validated risk calculator or standalone treatment algorithm, and decisions should balance absolute cardiovascular risk, major bleeding risk, evidence certainty, and patient preferences.
Coronary artery calcium (CAC) scoring has become an important tool for cardiovascular risk refinement in primary prevention and is increasingly used in both internal medicine and cardiology practice. By quantifying subclinical coronary atherosclerosis, CAC improves risk estimation beyond traditional risk factors and can help guide preventive strategies. Indeed, CAC tracks with actual risk more precisely than pooled equations and is a superior risk categorization tool. However, a growing clinical challenge is the tendency to use CAC score alone to support initiation of aspirin therapy. Although a high CAC score identifies patients with greater atherosclerotic burden and elevated long-term atherosclerotic cardiovascular disease (ASCVD) risk, it does not directly determine whether an individual patient is likely to derive net clinical benefit from aspirin. Contemporary primary prevention trials have demonstrated that aspirin provides only modest reductions in cardiovascular events while consistently increasing bleeding risk, resulting in a narrow therapeutic margin that is highly dependent on overall cardiovascular risk, bleeding susceptibility, and concomitant preventive therapies such as statins. In this focused review, we examine the available evidence linking CAC burden to aspirin benefit, discuss the limitations of CAC-guided treatment decisions, and propose a practical framework that integrates ASCVD risk, bleeding risk, and patient-specific clinical factors. We also identify key evidence gaps requiring prospective study. A more individualized approach to aspirin allocation may help clinicians avoid reflexive score-driven prescribing and better align preventive therapy with expected net benefit.
Zachary C Ahart, Richard C Becker· American Journal of Medicine· 0 citations
Prevention of atherosclerotic cardiovascular disease (ASCVD) is fundamental for both cardiologists and primary care physicians. From risk estimation to medical therapy for primary and secondary prevention, management is evolving with increasing evidence. Risk estimation is moving toward a model that emphasizes lifetime risk in addition to traditional shorter-term risk and takes a holistic view of individual patient cardiovascular risk, accounting for genetic predisposition and risk-enhancing comorbid conditions. Lipoprotein(a) and apolipoprotein B measurement and coronary artery calcification (CAC) scoring have emerged as tools for identifying residual risk and making decisions in cases of borderline risk. While statins remain foundational to management, newer treatment paradigms emphasize early intensification of therapy and addition of non-statin agents. These trends are reflected in recent guideline updates from the American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS). In the future, polygenic risk scoring and RNA-based therapies may offer opportunities to identify and treat those at highest residual risk.
Andrew Carlson, Zaid A. Zayyad, Stefanie Driesenga et al.· Cardiology and Therapy· 0 citations
Low‐dose aspirin is no longer routinely recommended for the primary prevention of cardiovascular disease in older adults due to a lack of net benefit over bleeding risk. We hypothesized that genetic subgroups may experience differential harm or benefit from aspirin therapy. To investigate this, we screened 572 polygenic scores (PGSs) for modification of aspirin's effect on major bleeding and major adverse cardiovascular events (MACE) in the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, placebo‐controlled trial of daily 100 mg aspirin. Participants were aged ≥70 years (≥65 years for US minorities) and free of cardiovascular disease, dementia, or physical disability at enrolment. Among participants with high‐quality genotyping data (n = 13,571), PGS–aspirin interactions were tested using Cox proportional hazards models with Bonferroni correction for multiple testing. During a median follow‐up of 4.6 years, 414 major bleeding events and 464 MACE occurred. A triglyceride‐related PGS (PGS003144) significantly modified aspirin‐associated bleeding (interaction P = 5.9 × 10−5; Bonferroni‐adjusted P = 0.034). In the lowest quintile of the PGS distribution, aspirin increased major bleeding risk (HR 2.28; 95% CI: 1.45–3.58; P = 0.00036), including separate bleeding subgroups gastrointestinal (HR 3.17; 95% CI: 1.48–6.80; P = 0.0029), and intracranial bleeding (HR 4.10; 95% CI: 1.54–11.0; P = 0.0049). In contrast, in the highest quintile, aspirin was associated with lower risk of bleeding (HR 0.62; 95% CI 0.38–0.97) and reduced MACE (HR 0.66; 95% CI 0.44–0.99). Baseline serum triglycerides showed similar effect modification. These hypothesis‐generating findings suggest triglyceride‐related genetic variation may identify individuals with differential responses to aspirin.
P. Fransquet, Chenglong Yu, C. Tran et al.· Clinical pharmacology and th...· 0 citations
Although there are conflicting clinical data on the efficacy of weight reduction in reducing secondary events in patients with comorbid overweight and obesity (OAO) and cardiovascular disease (CVD), there is excellent epidemiological and biological evidence of a cause-effect relationship between OAO, CVD, and other systemic complications. There is also new interventional evidence that pharmacotherapies improve cardiovascular, hepatic, and renal outcomes in individuals with OAO and pre-existing CVD. New trial data confirm that not all weight loss strategies are equal in terms of reducing cardiovascular risk. Using Global Burden of Disease data and a pooled analysis of registry data on ~30,000 patients with CVD, we estimate that about 34 million patients across the Middle East could benefit from secondary prevention of CVD by targeting OAO phenotypes. Implementing secondary prevention in practice will require updating clinical guidelines on both obesity management and CVD secondary prevention, as well as policy changes that allow for reimbursement. Crucially, it will also require a philosophical shift that there exist distinct OAO phenotypes for which treatment success is not solely dictated by weight loss. The cumulative burden of future cardiovascular risk is set to increase, mandating comprehensive strategies to implement secondary prevention in at-risk groups, including children.
W. Almahmeed, J. Barajas-Gamboa, M. Zubaid et al.· Obesity Reviews· 0 citations
Peripheral artery disease (PAD) is a prevalent manifestation of systemic atherosclerosis, associated with elevated risks of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Despite its clinical significance, PAD remains underdiagnosed and undertreated, reflecting substantial gaps in guideline implementation. This review highlights advances in the medical management of PAD, focusing on strategies targeting the metabolic, lipid, immuno-inflammatory, and thrombotic drivers of disease to improve cardiovascular and limb outcomes. Optimal management requires intensive, multifaceted approaches that integrate lifestyle modification (including smoking cessation, a healthy diet, and physical activity), risk factor control, and pharmacologic interventions. Dual pathway antithrombotic therapy with low-dose rivaroxaban and aspirin has emerged as a superior strategy to mitigate both cardiovascular and limb events in patients with high ischaemic risk and non-high bleeding risk. Statins are the first-line lipid-lowering therapy for all patients with PAD, and if low-density lipoprotein cholesterol (LDL-C) goals are not achieved with maximally tolerated doses, adjunctive agents-such as ezetimibe, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i)-should be added. Novel antidiabetic agents, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is), confer cardiovascular and renal benefits independent of glycaemic control, with emerging data suggesting that GLP-1 RAs may also reduce limb events. To date, semaglutide remains the only anti-obesity pharmacotherapy that has been demonstrated to reduce cardiovascular events in high-risk patients with overweight or obesity in the absence of diabetes. We propose a phenotype-driven approach to enable refined risk stratification across the PAD spectrum, supporting individualized and, when needed, more intensive management.
F. Garagoli, L. Slipczuk, Michael D. Shapiro et al.· European Heart Journal· 0 citations
Despite achieving guideline-recommended lipid levels, patients with atherosclerotic cardiovascular disease (ASCVD) retain substantial residual risk arising from heterogeneous biological pathways, including persistent inflammation and genetically determined atherogenic susceptibility. High-sensitivity C-reactive protein (hs-CRP) provides a pragmatic measure of potentially modifiable inflammatory activity, whereas lipoprotein(a) [Lp(a)] identifies relatively stable, genetically mediated risk that is not adequately captured by standard lipid panels. The 2025 American College of Cardiology Scientific Statement highlights hs-CRP as a clinically useful inflammatory-risk marker and supports consideration of low-dose colchicine in appropriately selected secondary-prevention patients. The 2026 ACC/AHA multisociety dyslipidemia guideline further provides a Class I recommendation for once-in-a-lifetime Lp(a) measurement, creating a complementary multimodal framework for residual-risk assessment. In China, where cardiovascular disease accounts for a substantial proportion of deaths and the national cardiovascular burden continues to increase, implementation of this framework remains limited. Routine hs-CRP measurement is uncommon, cardiovascular use of colchicine remains negligible, and Lp(a) testing is still concentrated in selected tertiary centers. Emerging East Asian data and a recent Chinese expert advisory suggest that an hs-CRP threshold of approximately 1.0 mg/L may improve inflammatory-risk discrimination in Chinese patients with coronary artery disease; however, this threshold should not yet be interpreted as a stand-alone treatment threshold for colchicine. In this perspective, we compare international recommendations with current Chinese practice, analyze barriers related to infrastructure, safety, education, standardization, and evidence localization, and propose a multimodal implementation framework. Short-term priorities include once-in-a-lifetime Lp(a) measurement, context-specific hs-CRP assessment, intensified management of modifiable atherosclerotic risk factors, and carefully selected use of low-dose colchicine in secondary prevention. Elevated Lp(a) should prompt comprehensive risk-factor intensification and, when appropriate, family-based evaluation, but should not by itself constitute an indication for colchicine. Medium- and long-term priorities include pragmatic trials, real-world registries, assay standardization, cost-effectiveness studies, and policy initiatives to integrate residual-risk assessment into Chinese cardiovascular prevention pathways.
Ming Chi, Tao-Ming Qian, Jirong Zhang et al.· Frontiers in Medicine· 0 citations
