India faces a rapidly evolving cardiometabolic risk landscape, with overweight and obesity affecting 23.5% and 6.7% of adults, alongside escalating hypertension, diabetes, and dyslipidemia. Central obesity, impacting 40% of women versus 12% of men, reflects the heightened visceral adiposity unique to Indians. Concurrent dietary shifts, pervasive tobacco use (28.6%, predominantly rural), and emerging lifestyle stressors demand attention; a recent Indian survey indicated that over half of young adults spend 1–3 hours daily on social media, with 31% reporting stress. These converging factors drive metabolic dysfunction, platelet hyperreactivity, and endothelial injury, highlighting the necessity for early antiplatelet strategies, including aspirin, in atherothrombotic risk mitigation, when appropriately indicated.
Potential Role of Aspirin in Lifestyle-Mediated Atherothrombosis
Lifestyle factors—tobacco use, psychosocial stress, unfavourable dietary transitions—perpetuate chronic low-grade inflammation, driving enhanced platelet activation through upregulated COX-1/thromboxane A₂ (TXA₂) biosynthesis. This creates a prothrombotic phenotype where platelet hyperreactivity persists despite optimal lipid and glycemic control (Figure 1), rendering aspirin's COX-1 inhibition as mechanistically critical.,\
Figure 1: Lifestyle Factors Drive COX-1-Mediated Atherothrombotic Risk
Aspirin in CV Event Prevention- Clinical Evidence:
Aspirin in High-Risk Primary Prevention-Recent AHA 2025 Update: The results of propensity analysis reported at the AHA Scientific Congress 2025, New Orleans, USA, indicated that aspirin significantly reduces cardiovascular events and mortality in Type 2 diabetes patients with moderate-to-high ASCVD risk. The analysis included 11,681 patients from an electronic health records (EHR) primary prevention registry across a large healthcare network (>400 sites), followed over 10 years, where 88.6% used aspirin. Results demonstrated moderate-to-high frequency aspirin use (≥30% adherence) yielded 42-58% reduction in MI/revascularization, 43-57% reduction in ischemic stroke, and high-frequency use (≥70% adherence) achieved 47% all-cause mortality reduction (HR 0.53, p<0.001). The benefits associated with aspirin amplified with better glycemic control, validating precision-based aspirin selection in targeted high-risk populations.
Aspirin in High CV-Risk Indian Patients: A prospective Indian study followed 420 patients with moderate-to-high cardiovascular risk for 24 months, validated aspirin's effectiveness in patients with heightened cardiometabolic burden. Aspirin significantly reduced cardiovascular events: while baseline risk scores predicted 14.8% would experience heart attacks or strokes, only 8.6% actually did. The breakdown showed 4.3% had non-fatal heart attacks, 2.9% had strokes, and 1.4% died from cardiovascular causes. The predicted 2-year MACE risk for diabetes was 17.5%, whereas the actual incidence was observed only in 10.2%. Over the 24-month study period, 75.7% of patients maintained consistent aspirin use (>80% adherence), confirming real-world feasibility in high CV risk Indian population.
Case Study: Lifestyle-Mediated Thrombotic Risk Patient Profile: 43-year-old IT manager from Bangalore, smoking 12 cigarettes daily (15 years), sedentary lifestyle with 10+ hours daily screen time, recent shift from home-cooked meals to frequent outside food, and work-related stress. Elder brother underwent angioplasty at age 48. Recently diagnosed with Type 2 diabetes (3 months ago). Clinical Data: BP 146/92 mmHg, WC 102 cm, FPG 142 mg/dl, PPG 210 mg/dl, HbA1c 7.1 %, LDL-C 145 mg/dL, HDL-C 34 mg/dL, TG 198 mg/dL. Qualifies per DCRM 2.0 2024 Recommendation: Multiple CV risk factors, including smoking, central obesity, dyslipidemia (low HDL—classic Indian phenotype), hypertension, and premature ASCVD family history (sibling).Meets ≥2 CV risk factor criteria. Thrombotic Assessment: Diabetes-associated platelet hyperreactivity amplified by tobacco-induced COX-1 upregulation and chronic stress-mediated inflammation creates a heightened atherothrombotic milieu. Aspirin's irreversible COX-1 inhibition directly addresses TXA₂-mediated platelet activation. Clinical Reasoning: Newly diagnosed diabetes with multiple concurrent risk factors drives accelerated atherothrombotic risk requiring a comprehensive prevention strategy. Bleeding Risk: No GI bleed history, normal renal function (eGFR 88 ml/min), no anticoagulant use, no history of peptic ulcer disease—favorable safety profile. Clinical Decision Making: Initiate aspirin alongside statin, lifestyle modification, and smoking cessation counseling—aligns with DCRM 2.0, USPSTF, and ACC/AHA guidance for targeted primary prevention in high-risk, lifestyle-burdened phenotypes., |
Take-Home Message
In India's lifestyle-driven cardiometabolic landscape, low-dose aspirin may have the potential to benefit appropriately selected high-risk patients fulfilling the DCRM 2.0 criteria (≥2 risk factors including central obesity, dyslipidemia, smoking, hypertension, family history of ASCVD). Consistent adherence appears to be associated with meaningful cardiovascular event reduction, supporting individualized risk-based decision-making for considering aspirin, as suggested by recent AHA and Indian real-world evidence.
Abbreviations: ACC/AHA - American College of Cardiology/American Heart Association, AHA - American Heart Association, ASCVD - Atherosclerotic Cardiovascular Disease, BP - Blood Pressure, CAC - Coronary Artery Calcium, CAD - Coronary Artery Disease, CKD - Chronic Kidney Disease, COX-1 - Cyclooxygenase-1, CRP - C-Reactive Protein, CV – Cardiovascular, DCRM - Diabetes, Cardiorenal, and Metabolic Diseases, EHR - Electronic Health Records, ESC - European Society of Cardiology, GI – Gastrointestinal, HbA1c - Hemoglobin A1c, HDL-C - High-Density Lipoprotein Cholesterol, HR - Hazard Ratio, IL-6 - Interleukin-6, LDL-C - Low-Density Lipoprotein Cholesterol, Lp(a) - Lipoprotein(a), MACE - Major Adverse Cardiovascular Events, MI - Myocardial Infarction, TNF-α - Tumor Necrosis Factor-alpha, TXA₂ - Thromboxane A₂, USPSTF - United States Preventive Services Task Force
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