Aspirin Use in Male Smokers Aged 40-45 Years with Hypertension: Identifying the Ideal Candidates

Premature ASCVD in India

In India, over 50% of cardiovascular disease (CVD) deaths occur before 50 years, and 25% of myocardial infarction (MI) events occur before 40 years. Registry data from India indicate that 31% of men undergoing percutaneous coronary intervention (PCI) are below 54 years, necessitating a shift toward lifetime ASCVD risk assessment. (1)

Epidemiology of Smoking and Hypertension in Young Indian Men

Smoking and hypertension are major contributors to cardiovascular risk among Indian men aged 40–45 years.(1) Smoking peaks between 35–49 years, with a mean initiation age of 45. Tobacco use affects 43% of rural and 29% of urban men.(2,3)

Hypertension is equally concerning in this group—52.8% of new diagnoses occur in those aged 40–49, with men accounting for 56.4%. Despite treatment, BP control remains suboptimal, with an adjusted odds ratio of 0.59–0.7, indicating poorer control in men. (4) (Figure 1)

Figure 1: The Double Burden: Smoking and Hypertension in Indian Men (40–49 Years)

Interaction of Smoking and Hypertension

• Accelerates Atherosclerosis: Smoking and hypertension synergistically increase vascular injury, advancing atherosclerosis onset by nearly a decade. (5)
• Increases Ambulatory BP and LV Mass: Smokers with hypertension show higher daytime BP and greater LV mass. (6)
• Higher All-Cause and CV Mortality: A prospective cohort of 3,468 hypertensive smokers showed a 76% increase in all-cause mortality [HR 1.76]. (7)

Pathophysiological Rationale for Aspirin Use

The synergistic risk from smoking and hypertension amplifies the rationale for antiplatelet therapy

• Smoking accelerates thrombogenic vascular injury, thus contributing to atherosclerosis. (5)
• Hypertension exacerbates endothelial damage and left ventricular mass increase, promoting thrombus formation and elevating cardiovascular risk.(6)
• Aspirin inhibits thromboxane A2, thereby reducing platelet aggregation and preventing thrombus formation. (8)

Evidence Supporting Aspirin in High-Risk Populations

• ASCEND Trial (N=15,480): Aspirin reduced major vascular events by 12% (RR 0.88; 95% CI, 0.79–0.97), demonstrating efficacy in those with multiple risk factors. (9)
• 2024 Lp(a) Study: Aspirin use was associated with a 52% reduction in ASCVD mortality (HR 0.48; 95% CI, 0.28–0.83) in those with elevated Lp(a) levels. (10)

Guideline Recommendations

• DCRM 2.0 (2024): Consider low-dose aspirin for adults aged 40–59 years at very high ASCVD risk, particularly with hypertension and smoking.  (11)
• USPSTF (2022): Aspirin initiation is recommended in adults aged 40–59 years with ≥10% ASCVD risk, provided bleeding risk is low. (12)
• ESC (2021): Low-dose aspirin may be used in high-risk individuals, especially smokers or hypertensives, with low bleeding risk.(12)
• ACC/AHA (2019): Low-dose aspirin can be considered in adults aged 40–70 years at high ASCVD risk without elevated bleeding risk. (12)

Clinical Case: Should Aspirin Be Initiated?

A 43-year-old man with a 10-year history of hypertension (on treatment) and active smoking presents for cardiovascular risk assessment. Laboratory evaluation shows LDL 142 mg/dL, HDL 38 mg/dL, and fasting glucose 104 mg/dL, with normal renal function and no prior ASCVD. He has no history of GI bleeding, peptic ulcer disease or related symptoms, NSAID/steroid use, and is clinically assessed to have a low bleeding risk. As per DCRM 2.0 (2024) guidelines, low-dose aspirin could be considered for initiation after excluding high bleeding risk to reduce major adverse cardiovascular events.

Tools like Aspiringuide can assist in systematically balancing cardiovascular benefit against possible bleeding risk, supporting shared decision-making in such high-risk profiles.

Clinical Implication

Targeted preventive strategies are essential to address the rising burden of premature cardiovascular disease among high-risk men aged 40–45 years. Compared to global patterns, Indian men indulge in smoking more often and have hypertension at a younger age, particularly in their 40s.

The selective initiation of low-dose aspirin, following a structured evaluation of cardiovascular and bleeding risks, is a pragmatic and evidence-backed approach for this high-risk population.

References:

1.Puri, Raman et al. “Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV.” Journal of clinical lipidology vol. 18,3 (2024): e351-e373. doi:10.1016/j.jacl.2024.01.006

2. Singh, S K et al. “Tobacco Use and Cessation among a Nationally Representative Sample of Men in India, 2019-2021.” Journal of smoking cessation vol. 2023 4292647. 22 Mar. 2023, doi:10.1155/2023/4292647

3. Rajdeep, P. S., Shigwan, S. R., & Gera, M. (2022). Prevalence of smoking in rural and urban areas in India: Systematic review. International Journal of Health Sciences, 6(S3), 6606²6616. https://doi.org/10.53730/ijhs.v6nS3.7472

4. Basu, Saurav et al. “Hypertension Control Cascade and Regional Performance in India: A Repeated Cross-Sectional Analysis (2015-2021).” Cureus vol. 15,2 e35449. 25 Feb. 2023, doi:10.7759/cureus.35449

5. Virdis, A et al. “Cigarette smoking and hypertension.” Current pharmaceutical design vol. 16,23 (2010): 2518-25. doi:10.2174/138161210792062920

6. Verdecchia, P et al. “Cigarette smoking, ambulatory blood pressure and cardiac hypertrophy in essential hypertension.” Journal of hypertension vol. 13,10 (1995): 1209-15. doi:10.1097/00004872-199510000-00016

7. Fagard, Robert H. “Smoking amplifies cardiovascular risk in patients with hypertension and diabetes.” Diabetes care vol. 32 Suppl 2,Suppl 2 (2009): S429-31. doi:10.2337/dc09-S354

8. Undas, Anetta et al. “Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions.” Blood vol. 109,6 (2007): 2285-92. doi:10.1182/blood-2006-01-010645

9. Santilli, Francesca et al. “Needs-based considerations for the role of low-dose aspirin along the CV risk continuum.” American journal of preventive cardiology vol. 18 100675. 15 Apr. 2024, doi:10.1016/j.ajpc.2024.100675

10. Razavi, Alexander C et al. “Aspirin use for primary prevention among US adults with and without elevated Lipoprotein(a).” American journal of preventive cardiology vol. 18 100674. 27 Apr. 2024, doi:10.1016/j.ajpc.2024.100674

11. Handelsman, Yehuda et al. “DCRM 2.0: Multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases.” Metabolism: clinical and experimental vol. 159 (2024): 155931. doi:10.1016/j.metabol.2024.155931

12. Della Bona R, Giubilato S, Palmieri M, Benenati S, Rossini R, Di Fusco SA, Novarese F, Mascia G, Gasparetto N, Di Monaco A, et al. Aspirin in Primary Prevention: Looking for Those Who Enjoy It. Journal of Clinical Medicine. 2024; 13(14):4148. https://doi.org/10.3390/jcm13144148

Abbreviations: CVD: Cardiovascular Disease, ASCVD: Atherosclerotic Cardiovascular Disease,MI: Myocardial Infarction, PCI: Percutaneous Coronary Intervention, OR: Odds Ratio, BP: Blood Pressure, NSAID: Nonsteroidal anti-inflammatory Drug, LV: Left Ventricle, HR: Hazard Ratio, RR: Relative Risk, Lp(a): Lipoprotein(a), ESC; European Society of Cardiology, USPSTF: U.S. Preventive Services Task Force, ACC/AHA: American College of Cardiology/American Heart Association, DCRM: Diabetes Cardio-Renal Metabolic Clinical Practice Guidelines