Lipid profile metabolism, pathophysiology, clinical correlations, and therapeutic strategies in cardiovascular and metabolic diseases

Abstract

Lipid abnormalities, encompassing dysregulations in cholesterol, triglycerides, and lipoprotein fractions, have emerged as pivotal modifiable risk factors for cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and other systemic conditions such as nonalcoholic fatty liver disease and chronic kidney disease. This review synthesizes current evidence on the molecular biology of lipid metabolism, including cholesterol biosynthesis and homeostasis, triglyceride synthesis and clearance, and the structure and function of lipoproteins—high-density lipoprotein (HDL) and low-density lipoprotein (LDL), with special emphasis on the atherogenic small dense LDL subfraction. Epidemiological, genetic, and clinical studies linking lipid profiles to disease pathology are critically examined, highlighting the causal and prognostic significance of lipid fractions beyond traditional metrics. The review also discusses advanced lipid markers, their utility in risk stratification, and the emerging concept of HDL dysfunction. Furthermore, correlations between lipid profiles and T2DM, NAFLD, cancer, inflammation, and other diseases are explored. Contemporary lifestyle and pharmacological interventions—ranging from statins, ezetimibe, and PCSK9 inhibitors to novel triglyceride-targeted therapies—are reviewed with respect to efficacy, safety, and guideline recommendations. Advances in precision medicine, including genetic testing and personalized lipid management, are also addressed. The evolving landscape of lipidology underscores the need for comprehensive, multifactorial approaches to lipid abnormalities to optimize patient outcomes and reduce residual cardiovascular and metabolic risk.