ЛІПОПРОТЕЇН (а) ЯК СУЧАСНИЙ МАРКЕР СЕРЦЕВО-СУДИННОГО РИЗИКУ: ВІД ПАТОФІЗІОЛОГІЇ ДО ТЕРАПЕВТИЧНИХ ПЕРСПЕКТИВ (ОГЛЯД ЛІТЕРАТУРИ)

Atherosclerotic cardiovascular diseases (ASCVD) remain the leading cause of mortality worldwide. Despite the widespread use of statins and the effective control of low-density lipoprotein cholesterol (LDL-C), a significant residual risk of cardiovascular events persists. In recent years, lipoprotein(a) (Lp(a)) has emerged as a critical, genetically determined risk factor. Approximately 20% of the global population has elevated Lp(a) levels (>50 mg/dL), which translates to increased susceptibility to coronary artery disease, ischemic stroke, and calcific aortic valve stenosis. Unlike traditional lipid risk factors, Lp(a) levels are largely resistant to lifestyle modifications and standard lipid-lowering therapies.The aim – to comprehensively analyze the current literature regarding the molecular structure, genetic regulation, and pathogenic mechanisms of Lp(a), specifically focusing on its proinflammatory properties mediated by oxidized phospholipids. Furthermore, the review aims to evaluate the clinical evidence linking Lp(a) to cardiovascular outcomes and to discuss the emerging landscape of RNA-targeted therapies and small molecule inhibitors.Results. Lp(a) is a hybrid lipoprotein consisting of an LDL-like particle covalently linked to apolipoprotein(a) (apo(a)), a homolog of plasminogen. Its pathogenicity is driven by three synergistic mechanisms: proatherogenic retention in the arterial wall, proinflammatory activation of the endothelium via oxidized phospholipids (OxPL), and potential antifibrinolytic effects. Current guidelines (AHA/ACC, EAS) recommend screening for Lp(a) at least once in a lifetime to stratify cardiovascular risk. While traditional therapies (statins, ezetimibe) have minimal impact on Lp(a), novel specific therapies are in advanced clinical development. Antisense oligonucleotides (pelacarsen) and small interfering RNAs (olpasiran, lepodisiran) have demonstrated potent dose-dependent reductions in Lp(a) levels (>80-90%) in phase 2 and 3 trials. Additionally, muvalaplin, the first oral small molecule inhibitor of Lp(a) formation, has shown promising results in phase 1 studies.Conclusions. Lp(a) represents a distinct and causal risk factor for ASCVD and aortic stenosis that requires specific attention in clinical practice. The upcoming completion of cardiovascular outcome trials will likely establish Lp(a)-lowering therapy as a new pillar of preventive cardiology.