Cardio-Metabolic Risk and Aspirin: What Does the Evidence Say for Indian Patients?
India carries a heavy cardiometabolic burden of nearly 30%, intensified by early-onset diabetes, hypertension, dyslipidaemia, and obesity patterns that extend beyond BMI. Among Indians with metabolically obese non-obese (MONO) and metabolically obese obese (MOO) phenotypes, relative CVD risk increases by about 77% (OR 1.77) and 92% (OR 1.92), respectively. Normal-weight central obesity also increases hypertension by about 55% (aOR≈1.55). All these risk factors lead to early CAD/ASCVD among young/middle-aged Indians.
In this landscape of metabolic dysfunction and early vascular disease, aspirin’s antiplatelet and anti-inflammatory effects may offer selective preventive value for carefully risk-stratified cardiometabolic patients.
Metabolic Crisis to Thrombosis-Pathophysiological Interactions
The metabolic dysfunction in Asian Indians represents more than a cluster of risk factors—it is a biologically active state that accelerates endothelial injury and atherothrombosis. Obesity, insulin resistance, and dyslipidaemia create a pro-inflammatory, pro-thrombotic milieu marked by low adiponectin, high leptin, elevated CRP, small-dense LDL, and raised PAI-1, driving endothelial dysfunction, impaired fibrinolysis, and early CV events.
Since inflammation and thrombosis lie at the core of this cardiometabolic risk, an agent that acts at this biological intersection seems clinically relevant. Aspirin, long used in atherosclerosis and ACS, irreversibly inhibits COX-1, suppressing thromboxane A₂-mediated platelet activation and tempering the coagulation cascade driven by thrombin, ADP, and TP-receptor signalling. By dampening both inflammatory and platelet pathways, aspirin appears to intervene precisely at this convergence point.
Aspirin in CV Risk Prevention: Evidence Review
Among contemporary prevention trials, the ASCEND study offers important insight into a key clinical question: Does aspirin help prevent first cardiovascular events in high-risk cardiometabolic patients? Conducted in 15,480 adults with diabetes, an established cardiometabolic high-risk group without known CVD, the trial randomized participants to aspirin 100 mg daily or placebo over 7.4 years. Aspirin produced a 12% relative reduction in major cardiovascular events (absolute reduction 1.1%), nearly balanced by an absolute bleeding increase of 0.9%. These findings reaffirm that in cardiometabolic patients, such as those with diabetes, aspirin for primary prevention must be carefully individualized.In India, where cardiometabolic risks accumulate earlier and substantially elevate ASCVD risk among young and middle-aged adults, the potential preventive benefit of aspirin may be relatively greater, particularly in those with lower baseline bleeding risk.
Translating Evidence into Practice Guidance – Whom to Consider for Aspirin?
The table below summarizes key recommendations (Table 1):
Table 1: Guideline Recommendations for Aspirin
Guideline | Recommendations for Aspirin |
DCRM (2024) | Suggest low-dose aspirin in Individuals with ≥2 CV risk factors: elevated non-HDL-C, LDL-C, Lp(a), reduced HDL-C, diabetes, hypertension, CKD, smoking, family history of ASCVD, or CAC score >100 |
USPSTF (2022) | Adults 40–59 years with ≥10% 10-year ASCVD risk |
ESC (2021)8 | High overall cardiovascular risk |
ACC/AHA (2019)8 | Adults 40–70 years with elevated ASCVD risk |
Practical Decision-Making Framework for Aspirin Use
Case Scenario: A 47-year-old Indian male with T2D, hypertension, and central obesity, with elevated CRP and intermittent smoking. Despite ongoing lipid-lowering therapy, LDL-C has not reached guideline targets. This profile reflects a multi-risk cardiometabolic individual with accelerated atherosclerotic risk. Bleeding Risk Assessment: No prior gastrointestinal bleeding, no peptic ulcer disease, no anticoagulant therapy, normal renal function, and age below 70 years, all suggestive of low bleeding risks. Clinical Interpretation: In patients with multiple cardio-metabolic risks and low bleeding propensity, low-dose aspirin may be considered after shared decision-making, individualized through balancing ASCVD benefit against bleeding risk. |
Tools such as AspirinGuide can further assist clinicians in estimating bleeding risk and guiding shared decision-making.
Take Home Message
In Indian patients with a high cardiometabolic burden, the overlap of metabolic dysfunction, inflammation, and thrombosis highlights where aspirin’s anti-inflammatory and antiplatelet effects may offer selective CV prevention benefit. Used within a risk-based framework and with careful bleeding assessment, aspirin could be considered in appropriately stratified cardio-metabolic risk patients for CV event protection.
Abbreviations: ACS – Acute Coronary Syndrome, ACC/AHA – American College of Cardiology/American Heart Association, ADP – Adenosine Diphosphate, ASCEND – A Study of Cardiovascular Events in Diabetes, ASCVD – Atherosclerotic Cardiovascular Disease, aOR – Adjusted Odds Ratio, BMI – Body Mass Index, CAC – Coronary Artery Calcium, CKD – Chronic Kidney Disease, COX-1 – Cyclooxygenase-1, CRP – C-reactive Protein, CV – Cardiovascular, CVD – Cardiovascular Disease, DCRM – Diabetes Care & Research Management (2024 guideline), DM – Diabetes Mellitus, ESC – European Society of Cardiology, HDL-C – High-Density Lipoprotein Cholesterol, LDL-C – Low-Density Lipoprotein Cholesterol, Lp(a) – Lipoprotein(a), MOO – Metabolically Obese Obese, MONO – Metabolically Obese Normal Weight, MS – Metabolic Syndrome, non-HDL-C – Non-High-Density Lipoprotein Cholesterol, OR – Odds Ratio, PAI-1 – Plasminogen Activator Inhibitor-1, TP receptor – Thromboxane Prostanoid Receptor, T2DM – Type 2 Diabetes Mellitus, USPSTF – United States Preventive Services Task Force, WC – Waist Circumference
Dr. Deepak Gupta, MBBS, MD (Medicine), DM (Cardiology), is an interventional cardiologist with over 25 years of clinical experience. He has been awarded the Fellowship of the Society for Coronary Angiography and Interventions (FSCAI), USA, and is also a Fellow of the European Society of Cardiology (FESC), Europe. Dr. Deepak Gupta is currently practicing at Dr. Deepak Gupta Cardiologist and Health Centre, Ranchi, Jharkhand.
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