The Past, Present, and Future of Dyslipidemia: A Narrative Review

Cardiovascular disease (CVD) remains the leading global cause of death, with dyslipidemia as its most modifiable driver of atherosclerotic CVD. The burden is especially severe in India, where early-onset disease and a distinct lipid profile, marked by elevated triglycerides, low high-density lipoprotein cholesterol (HDL-C), and small dense low-density lipoprotein (sdLDL) particles, contribute to increased lifetime risk. The pathophysiology of atherosclerosis has evolved from the cholesterol-centric model to the response-to-retention hypothesis, highlighting the role of apolipoprotein B (ApoB)-containing lipoproteins in initiating vascular inflammation and plaque formation. Advances in lipid science have revealed complex interactions between lipid metabolism, endothelial dysfunction, and immune activation. The Lipid Association of India 2023 guidelines recommend lifetime risk-based assessment and early intervention using coronary artery calcium scoring (CACS), carotid and femoral plaque imaging, and ankle-brachial index (ABI) to refine risk stratification. Therapeutic options have expanded beyond statins to include ezetimibe, PCSK9 inhibitors, bempedoic acid, and RNA-based agents, offering deeper and safer lipid reduction. Emerging therapies targeting ANGPTL3, liver X receptor (LXR) β, and PPAR-β/δ pathways promise further innovation in lipid modulation. These developments mark a shift toward precision lipidology, integrating genomics, imaging, and long-acting therapeutics to enable early, aggressive, and individualized prevention. As India faces a rising tide of cardiovascular events in younger populations, the future of lipid management lies in personalized, multimodal strategies that address both traditional and residual risk, aiming for sustained cardiovascular protection and improved public health outcomes.