Aspirin in Obese T2D with Atherogenic Dyslipidemia: Identifying the Ideal Candidates

India faces a rapidly escalating triple syndemic of obesity, type 2 diabetes (T2D), and atherogenic dyslipidemia, conditions that frequently overlap and amplify each other’s cardiovascular risks. More than 90% of diabetics are estimated to have an atherogenic lipid profile. [1] Even “lean” Indians with NAFLD often demonstrate visceral fat accumulation, insulin resistance, and platelet-driven inflammatory risk similar to that seen in obesity. [2] Around 41.9% of Indians with T2D and dyslipidemia already show evidence of atherogenic dyslipidemia. [3]

Patients presenting with this combination of obesity, T2D, and dyslipidemia face roughly a 1.4-fold higher risk of major cardiovascular events, including myocardial infarction and stroke, compared with those having normal lipid profiles, even when blood pressure is well controlled. [4] In addition, elevated lipoprotein(a) [Lp(a)] contributes an independent, genetically determined atherogenic burden. High Lp(a) is found in over a quarter of Indian T2D patients, with levels increasing as diabetes duration lengthens. [5] This article explains why this uniquely high-risk Indian phenotype may warrant earlier aspirin consideration. Understanding the underlying pathophysiological interactions further clarifies this rationale.

Pathophysiological Interactions: When Obesity Meets Platelet Hyperreactivity

Insulin resistance, visceral adiposity, and chronic low-grade inflammation generate ROS and cytokines such as TNF-α, IL-6, and CRP, driving endothelial dysfunction and heightened platelet reactivity. Atherogenic dyslipidemia accelerates small dense LDL-mediated plaque instability even before overt ASCVD. In this context, low-dose aspirin’s antiplatelet action becomes clinically relevant for interrupting platelet activation before primary cardiovascular events. [6,7,8]

Who Actually Benefits? Ideal Indian Candidate Profile for Aspirin

Aspirin’s mechanism seems relevant to obese, insulin-resistant T2D patients with high triglycerides, low HDL-C, elevated non-HDL cholesterol, or elevated Lp(a), a subgroup characterized by heightened thromboxane-mediated platelet activation and inflammation. This lipid–inflammatory profile is distinct and not universal to all diabetes, reinforcing the need for precise risk stratification rather than blanket aspirin use. [5,9,10] Aspirin is clinically relevant when ASCVD-related macrovascular risk clearly outweighs bleeding concerns, particularly in Indians with early vascular stiffness, or a strong family history of positive and/or premature ASCVD. In such predisposed lipid–inflammatory states, platelet activation emerges early, making aspirin consideration appropriate for carefully selected high-risk profiles. [11]

Guideline Positioning: Where Aspirin Fits Today

Current guidance from USPSTF, ESC, AHA/ACC, and DCRM 2024 supports individualized low-dose aspirin use. [12] The DCRM 2.0 guidelines recommend considering aspirin when two or more difficult to modify CV risk enhancers are present (including elevated non-HDL-C, elevated LDL-C, elevated Lp(a), low HDL-C, diabetes, hypertension, CKD, cigarette smoking, family history of ASCVD, elevated CAC score >100) and bleeding risk is low.[11] The new ESC 2025 (ESC Congress 2025, Madrid) update further strengthens this position by formally recognizing elevated Lp(a) as a causal risk factor where aspirin has shown meaningful ASCVD risk reduction. [13]

A meta-analysis involving 49,871 participants presented at ESC Congress 2025 showed that aspirin significantly reduced major adverse cardiovascular events in individuals with elevated Lp(a) ≥50 mg/dL (HR 0.51; 95% CI 0.35–0.75) and in rs-3798220-C/LPA variant carriers (HR 0.59; 95% CI 0.36–0.98), without a rise in bleeding risk, further supporting aspirin’s role in primary prevention for genetically or biochemically high-Lp(a) populations. [14]

Key Messages

India’s metabolic phenotype is uniquely high risk, with obesity, type 2 diabetes, and atherogenic dyslipidemia; often also present even in lean individuals with NAFLD, and platelet hyperreactivity emerging early with high triglycerides, low HDL-C, or elevated Lp(a). In such high-risk profiles, aspirin use may be considered when macrovascular ASCVD risk seems dominant over bleeding risk, through a systematic individualized approach.

Abbreviations: AD – Atherogenic Dyslipidemia, ACS – Acute Coronary Syndrome, AHA – American Heart Association, ASCVD – Atherosclerotic Cardiovascular Disease, CAC – Coronary Artery Calcium, CKD – Chronic Kidney Disease, CRP – C-Reactive Protein, CV – Cardiovascular, DCRM – Diabetes Cardiometabolic Risk Management, ESC – European Society of Cardiology, HDL-C – High-Density Lipoprotein Cholesterol, IL-6 – Interleukin-6, LDL-C – Low-Density Lipoprotein Cholesterol, Lp(a) – Lipoprotein(a), MI – Myocardial Infarction, NAFLD – Non-Alcoholic Fatty Liver Disease, PCOS – Polycystic Ovary Syndrome, ROS – Reactive Oxygen Species, T2D – Type 2 Diabetes, TG – Triglycerides, TNF-α – Tumor Necrosis Factor-alpha, USPSTF – United States Preventive Services Task Force