Features of Lipid Disorders in Cardiovascular-Kidney-Metabolic Syndrome

Cardiovascular-kidney-metabolic (CKM) syndrome is driven by the interplay of visceral adiposity, insulin resistance, chronic inflammation, oxidative stress, and progressive kidney dysfunction. These mechanisms generate a distinct atherogenic dyslipidaemic phenotype characterised by elevated triglycerides (TG), reduced high-density lipoprotein-cholesterol (HDL-C), increased apolipoprotein B (apoB)-containing lipoproteins, remnant cholesterol (RC) accumulation, small dense low-density lipoprotein (LDL) particles, and frequently elevated lipoprotein(a) [Lp(a)]. Such lipid abnormalities contribute to accelerated atherosclerosis and early renal deterioration. In turn, kidney dysfunction further amplifies lipid abnormalities. These pathways underscore the need for a timely and comprehensive lipid assessment using apoB, non-HDL-C, RC, and Lp(a) within the CKM framework. Effective lipid management is crucial for CKM syndrome treatment, with the potential to reduce residual cardiovascular and renal risk and improve long-term clinical outcomes. In this narrative review, we examine current evidence on the pathophysiological mechanisms underlying CKM-related dyslipidaemia and provide a practical framework for its assessment and management. Management requires a multimodal approach tailored to the patient's lipid phenotype and overall cardiovascular risk, incorporating a range of lipid-lowering strategies including statins, ezetimibe, PCSK9 inhibitors, bempedoic acid, fibrates, icosapent ethyl, and emerging therapies targeting apoC-III, ANGPTL3, and Lp(a). Beyond lipid lowering, lifestyle interventions and cardiometabolic therapies such as glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, and finerenone may provide complementary cardiometabolic and renal protection.