Need for population-specific lipid guidelines for South Asians: Focus on the Indian population and its distinct cardiometabolic risk profile

BACKGROUND South Asian individuals bear a disproportionately high burden of atherosclerotic cardiovascular disease (ASCVD), characterized by earlier onset, greater severity, and higher mortality compared with Western populations. This is despite lower average low-density lipoprotein cholesterol (LDL-C) levels and is driven by a distinctive cardiometabolic phenotype, including adverse lifestyle factors, high prevalence of insulin resistance and diabetes, hypertriglyceridemia, increased small dense LDL particles, elevated lipoprotein(a), and low high-density lipoprotein cholesterol (HDL-C) levels. OBJECTIVE To review the cardiometabolic risk profile of South Asians and the rationale for population-specific lipid management strategies, with a focus on contemporary evidence and recommendations from the Lipid Association of India (LAI). METHODS The relevant evidence was identified from published prospective cohort studies, randomized controlled trials, meta-analyses, and international and Indian guidelines with emphasis on studies evaluating South Asian/ Indian populations. The literature was evaluated with specific attention to differences in ASCVD burden, age at disease onset, cardiometabolic risk factors, lipid and lipoprotein profiles, and treatment responses between South Asian/Indian and Western populations. Evidence supporting intensive LDL-C lowering and combination lipid-lowering therapy was reviewed. RESULTS South Asians demonstrate a high prevalence of atherogenic dyslipidemia characterized by hypertriglyceridemia, low HDL-C, elevated non-HDL-C, and increased apolipoprotein B (apo B) containing particles, often with relatively modest LDL-C levels. Western risk prediction models and lipid thresholds may therefore underestimate ASCVD risk in this population. LAI guidelines recommend lower LDL-C targets than Western counterparts, refined ASCVD risk stratification including extreme-risk group categories, and the use of non-HDL-C and apo B as complementary therapeutic targets. Combination lipid-lowering therapy with statins, ezetimibe, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 inhibitors is often required to achieve recommended goals and address residual lipid-related risk. CONCLUSION Given the distinctive cardiometabolic profile and high ASCVD burden, population-specific lipid guidelines are essential. Intensive LDL-C and non-HDL-C lowering, comprehensive risk stratification, and early combination therapy, alongside sustained lifestyle modification and optimal management of comorbidities, are key strategies to mitigate the growing epidemic of ASCVD in South Asian populations.