Young, Diabetic, and at High CV Risk: Is It Time for Early Aspirin?
Young, Diabetic, and at High CV Risk: A Case for Early CV Prevention with Aspirin in the High-Risk Young
The Rising Cardio-Metabolic Tide in India
Cardiovascular disease (CVD) remains the leading cause of death in India, responsible for 26.6% of total mortality, with a strikingly earlier onset—nearly a decade ahead of Western populations—and over 60% of deaths occurring prematurely. (1) This growing crisis is fueled by poor control of cardio-metabolic risk factors, rising obesity, and low awareness or treatment of diabetes and hypertension. (2)
Younger individuals (ages 20–50), especially men, are increasingly affected by myocardial infarctions linked to hypertension, smoking, and central obesity. (3)
The unique “thin-fat” Indian phenotype, characterized by central adiposity at lower BMI levels, amplifies insulin resistance, metabolic syndrome, and early atherosclerosis, forming an interconnected and escalating pathophysiological burden that traditional risk assessments often fail to detect. (4,5)
Clinical Profile of a Young, High-Risk Patient: A 36-year-old male, corporate professional with early-onset diabetes presents with multiple CV risk factors, including a family history of sudden cardiac death, dyslipidemia, and a history of smoking. Despite a normal BMI and WC > 91 cm, central obesity and insulin resistance are evident. He is highly susceptible to premature and extensive CAD, with a possible risk of developing triple-vessel disease at a young age.
Why Traditional Risk Factor Prevalence Alone Isn’t Enough
Young patients may often present with ACS without prior angina or symptoms. Accelerated atherothrombosis, endothelial dysfunction, and heightened platelet reactivity are known contributors to CVD events in the absence of obstructive disease. Underlying inflammation, vasoconstriction, and platelet hyper-reactivity contribute to a prothrombotic state. (6,7)
In young CVD/CAD patients, diagnosis is challenging due to subtle early symptoms, normal LV function, and atypical presentations, making stress tests less revealing.
Though revascularization is often needed, emergent surgery increases the risks of bleeding, ventilation, and hospital stay. Long-term graft patency is also a concern. Persistent cardiometabolic risk factor burden continues to drive atherosclerosis progression despite intervention. (7)
The QRISK 3, calculated based on parameters such as age, ethnicity, weight, and height, (8) with “Indian” included as an ethnicity option, making it appropriate for identifying high-risk individuals in the Indian population, where age-related increases in coronary calcium and risk scores have shown statistically significant associations. (9) The TyG index demonstrated a very strong association (r = 0.90, p < 0.001) with atherogenic dyslipidemia, including elevated triglycerides, decreased HDL-C, and indirectly small dense LDL particles in T2DM patients with poor glycemic control. (10)
The Role of Early Prevention with Aspirin – Building the Shield
Aspirin exerts its antiplatelet effect by irreversibly inhibiting COX-1, thereby suppressing thromboxane A2 production and reducing platelet aggregation. While firmly established in secondary prevention of ASCVD, it may be considered for primary prevention in high CV risk individuals, particularly when the bleeding risk is low, guided by clinical judgment and individualized risk-benefit assessment. (11)
In the TIPS-3 trial, adding aspirin to standard care reduced the composite of CV death, MI, stroke, cardiac arrest, HF, or revascularization by 31% (HR 0.69, 95% CI 0.50–0.97), supporting additive benefit alongside lifestyle interventions and standard care. (11)
Clinical Pearls:
The American College of Cardiology/American Heart Association (ACC/AHA) and the USPSTF provide recommendations on the use of aspirin for primary prevention of CVD
The greatest benefit is observed in adults with elevated Lp(a) (≥50 mg/dL), where aspirin use is associated with a 52% reduction in ASCVD mortality. (11)
The 2024 DCRM 2.0 recommends low-dose aspirin for primary prevention in individuals with two or more risk factors, such as high Lp(a), LDL-C, diabetes, hypertension, smoking, or a family history of ASCVD, when the bleeding risk is low. (12)
A risk–benefit evaluation remains essential, and decision-support tools like AspirinGuide can aid clinicians in balancing benefits and bleeding risks in such high-risk individuals.
Conclusion—Before the Storm Hits: In young adults, CVD often begins silently, especially in those with a family history, early-onset diabetes, or features of metabolic syndrome, making timely prevention critical. In selected high-risk individuals, low-dose aspirin provides a safe, cost-effective, and impactful strategy for preventing premature major CV events.
Abbreviations: CVD – Cardiovascular Disease, CV – Cardiovascular, BMI – Body Mass Index, MI – Myocardial Infarction, ACS – Acute Coronary Syndrome, CAD – Coronary Artery Disease, ASCVD – Atherosclerotic Cardiovascular Disease, COX-1 – Cyclooxygenase-1, Lp(a) – Lipoprotein(a), TIPS-3 – International Polycap Study 3, HF – Heart Failure, TyG index – Triglyceride-Glucose Index, LV – Left Ventricular, HR – Hazard Ratio, CI – Confidence Interval
References
1. Kalra A, et al. The burgeoning cardiovascular disease epidemic in Indians – perspectives on contextual factors and potential solutions. Lancet Regional Health Southeast Asia 2023;12:100156.
2. Nila, Sindhu et al. “Changes in Cardiometabolic Risk Factors Over Two Decades in a Rural Population in Western India.” Indian journal of public health vol. 69,2 (2025): 159-165. doi:10.4103/ijph.ijph_488_24
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6. Alfaddagh, Abdulhamied et al. “Inflammation and cardiovascular disease: From mechanisms to therapeutics.” American journal of preventive cardiology vol. 4 100130. 21 Nov. 2020, doi:10.1016/j.ajpc.2020.100130
7. Wang, Xia, and Ben He. “Endothelial dysfunction: molecular mechanisms and clinical implications.” MedComm vol. 5,8 e651. 22 Jul. 2024, doi:10.1002/mco2.651
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9. Chandrawanshi V, Gaikwad NR, Keche Y, et al. Ten-Year Cardiovascular Risk as Predicted by the QRISK®3 Calculator in Diabetic Patients Attending a Tertiary Care Teaching Hospital in Central India and Its Application to Stratify Statin Over-Users and Under-Users. Cureus 2023;15(10):e47213
10. Gajjar M, Mishra M K, Shah T J, et al. (March 31, 2025) Triglyceride-Glucose Index and Atherogenic Index as Alternative Biomarkers for Glycemic Control in Type 2 Diabetes Mellitus. Cureus 17(3): e81550. DOI 10.7759/cureus.81550
11. Della Bona, R.; Giubilato, S.; Palmieri, M.; Benenati, S.; Rossini, R.; Di Fusco, S.A.; Novarese, F.; Mascia, G.; Gasparetto, N.; Di Monaco, A.; et al. Aspirin in Primary Prevention: Looking for Those Who Enjoy It. J. Clin. Med. 2024, 13, 4148. https://doi.org/10.3390/jcm13144148
12. 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
