Identifying Aspirin Candidates for Primary Prevention: Focus on Men Aged 40- 50 with Metabolic Syndrome and Cardiometabolic Risk

Unique CV Risk in India- Epidemiological Backdrop

Cardiovascular diseases (CVDs) remain the leading cause of death in India, with a WHO-reported age-adjusted CVD mortality rate of 349 per 100,000 men. (1) NFHS-5 data show that Indian men aged 40–49 have nearly four times the odds of heart disease compared to adolescents. (2) Moreover, 1.1% of Indian men meet IDF criteria for metabolic syndrome, doubling the risk of CVD and increasing stroke and CVD mortality risk by 1.5-fold. (3,4) These findings underscore the need for individualized primary prevention strategies, such as illustrated in the case scenario.

Why is this case a High CV-Risk?

Hypertension: Contributes to 48% of strokes and 18% of coronary events. (5)

Central Obesity: Visceral fat promotes inflammatory markers (↑FFA, IL-1, IL-6, TNF-α); ↓adiponectin. (6)

High Triglycerides: Contribute to foam cell formation and early atherogenesis. (7)

Elevated TyG Index: Associated with a 33% higher risk of cardiovascular events. (7)

Prediabetes (IFG): Raises the incidence of MACCE to 27.3% vs. 18.4% in normoglycemic individuals. (8)

Ethnicity: South Asian males have significantly higher rates of dyslipidemia and hypertension compared to women, necessitating earlier preventive strategies.(9)

Aspirin in Primary Prevention- Rationale & Guideline Recommendations: Aspirin reduces primary cardiovascular events through irreversible COX-1 inhibition in platelets, decreasing thromboxane A2 production, and reducing platelet aggregation. Additionally, it may lower Lp(a) concentrations by suppressing hepatic apo(a) mRNA expression. (10)

The DCRM (2024) advocates considering low-dose aspirin for primary prevention when patients present with two or more cardiovascular risk factors—such as elevated non-HDL-C, LDL-C, Lp(a), reduced HDL-C, diabetes mellitus, hypertension, chronic kidney disease, smoking, family history of ASCVD, or coronary artery calcium score >100. (11) The USPSTF (2022) endorses aspirin initiation in adults aged 40–59 years with ≥10% 10-year ASCVD risk, whereas ESC (2021) recommends therapy when overall CV risk is high, and ACC/AHA (2019) broadens consideration to individuals aged 40–70 years with elevated ASCVD risk.(10)

All guidelines emphasize that cardiovascular benefits must outweigh bleeding risks, requiring careful assessment and monitoring. Tools like AspirinGuide help clinicians evaluate bleeding risk and support shared decision-making.

Key Takeaway

Men aged 40–50 with metabolic syndrome and multiple CV-metabolic risk factors may represent a prudent consideration as a candidate for primary prevention with aspirin therapy, provided bleeding risk remains acceptably low. The decision must remain individualized, carefully weighing the CV benefits against the bleeding risks through shared decision-making and the use of appropriate risk assessment tools.

Abbreviations: ASCVD – Atherosclerotic Cardiovascular Disease, CVD – Cardiovascular Disease, MI – Myocardial Infarction, LDL-C – Low-Density Lipoprotein Cholesterol, HDL-C – High-Density Lipoprotein Cholesterol, TG – Triglycerides, BP – Blood Pressure, COX-1 – Cyclooxygenase-1, CAC – Coronary Artery Calcium, CKD – Chronic Kidney Disease, DCRM – Diabetes, Cardiorenal, and/or Metabolic (platform/consensus), USPSTF – United States Preventive Services Task Force, ESC – European Society of Cardiology, AHA/ACC – American Heart Association / American College of Cardiology, FFA - Free Fatty Acids IL-1 - Interleukin-1 IL-6 - Interleukin-6 TNF-α - Tumor Necrosis Factor-alpha, IDF - International Diabetes Federation NFHS-5 - National Family Health Survey-5 MACCE - Major Adverse Cardiovascular and Cerebrovascular Events

Reference

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2. Ram, Sumit, et al. "Prevalence and determinants of self-reported heart disease among Indian men aged 15–54 years: Evidence from NFHS-5." Clinical Epidemiology and Global Health, vol. 23, Sept.–Oct. 2023, 101374. Elsevier, https://doi.org/10.1016/j.cegh.2023.101374.

3. Meher, Trupti, and Harihar Sahoo. “The Epidemiological Profile of Metabolic Syndrome in Indian Population: A Comparative Study between Men and Women.” Clinical Epidemiology and Global Health, vol. 8, no. 4, Dec. 2020, pp. 1047–52.

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7. Kazibwe, Richard. “Triglyceride-Glucose Index and Cardiovascular Events in Non-Diabetic Hypertension: Secondary Analysis of SPRINT.” American Journal of Preventive Cardiology, vol. 19, Supplement, Sept. 2024, 100740.

8. Zhao, X., Zhuang, Y., Tang, S. et al. Prognostic impact of prediabetes on long-term cardiovascular outcomes in patients under 35 with premature acute myocardial infarction. Diabetol Metab Syndr 17, 90 (2025). https://doi.org/10.1186/s13098-025-01662-3

9. Agarwala, Anandita et al. “Cardiovascular Disease Risk in South Asians in the Baylor Scott and White Health DILWALE Registry.” JACC. Advances vol. 3,12 101349. 30 Oct. 2024, doi:10.1016/j.jacadv.2024.101349

10. Della Bona, Roberta et al. “Aspirin in Primary Prevention: Looking for Those Who Enjoy It.” Journal of clinical medicine vol. 13,14 4148. 16 Jul. 2024, doi:10.3390/jcm13144148

11. Handelsman Y, Anderson JE, Bakris GL, et al. DCRM 2.0: Multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases. Metabolism. 2024;159:155931. doi:10.1016/j.metabol.2024.155931