Lipoprotein(a) as a risk factor in young patients with Myocardial Infarction: Pathophysiology, clinical implications, and therapeutic perspectives

Elevated lipoprotein(a) [Lp(a)] is increasingly recognized as a genetically determined, independent risk factor for premature myocardial infarction (MI). Unlike traditional atherosclerotic risk markers, Lp(a) contributes to both atherogenesis and thrombosis through its unique structural and biochemical properties, including proinflammatory oxidized phospholipids and apo(a)-mediated antifibrinolytic activity. Young patients with high Lp(a) frequently present with distinctive phenotypes characterized by multivessel involvement, soft thrombotic plaques, minimal calcification, and abrupt clinical events, often in the absence of conventional risk factors. Epidemiologic studies and clinical registries consistently demonstrate an elevated relative risk of MI in individuals with elevated Lp(a), particularly when small apo(a) isoforms are present or familial hypercholesterolemia coexists. Current clinical guidelines emphasize targeted screening in high-risk populations, yet standardized assay methodologies and universal reference thresholds remain evolving. Therapeutic strategies to lower Lp(a) include conventional lipid-lowering agents, PCSK9 inhibitors, and emerging RNA-based therapies, which show promising reductions in circulating Lp(a) levels and potential mitigation of cardiovascular risk. Despite growing evidence, critical gaps persist regarding threshold definitions, optimal screening strategies, and long-term outcomes of Lp(a)-lowering interventions. This review synthesizes current knowledge on the pathophysiology, epidemiology, clinical phenotypes, and therapeutic implications of elevated Lp(a) in young MI patients, highlighting opportunities for personalized risk assessment and next-generation preventive strategies.