Lipoprotein(a) as a Cardiovascular Risk Factor: Clinical Significance and Therapeutic Perspectives

Lipoprotein(a) (Lp(a)) is an elusive yet powerful cardiovascular risk factor, largely independent of LDL cholesterol. Elevated Lp(a) increases the risk of coronary artery disease, stroke, peripheral arterial disease, calcific aortic valve disease, heart failure, and abdominal aortic aneurysm. The challenge is that conventional lipid-lowering therapies have minimal impact on Lp(a), leaving patients with substantial residual risk. While observational and genetic studies generally support Lp(a) as a driver of cardiovascular events, results are not entirely consistent, and risk may differ between primary and secondary prevention. Novel therapies—including antisense oligonucleotides, siRNA therapeutics, CETP inhibitors, and experimental gene-editing approaches—show promising potential, reducing Lp(a) levels by up to 90%. Ongoing phase III trials will clarify whether these reductions translate into meaningful decreases in cardiovascular morbidity and mortality. This review critically examines the current evidence, highlights gaps in knowledge, and discusses emerging therapeutic strategies, emphasizing the need for individualized risk assessment. Lp(a) may soon shift from a “silent threat” to a precise, actionable target in cardiovascular prevention.