The role of lipoprotein (a) in premature cardiovascular disease: primed for prevention

Elevated Lp(a) is an independent, causal, genetic cardiovascular disease risk factor that is associated with the progression of high-risk coronary plaques. Risk of atherosclerotic cardiovascular disease (ASCVD)-related conditions, which are among the leading causes of death worldwide, may persist in individuals with elevated Lp(a), even in the presence of at-target, guideline recommended-low-density lipoprotein-cholesterol levels. The prevalence of premature ASCVD, often defined as an ASCVD event occurring in men <55 years old and in women <65 years old, is increasing, and several studies support Lp(a) playing a significant role in the development of premature ASCVD. Despite recognition of Lp(a) as a genetic risk factor for ASCVD and recommendations for universal Lp(a) testing in multiple clinical guidelines, Lp(a) testing occurs infrequently in clinical practice. In this review, we examine the role of elevated Lp(a) in premature cardiovascular events, including premature myocardial infarction, stroke, and peripheral arterial disease. We discuss the potential benefit of universal Lp(a) testing in the context of primary prevention to enable personalised risk assessment and to identify high-risk patients who may benefit from early and targeted management. Further, we evaluate ongoing systems initiatives aiming to a) address barriers to the adoption of universal Lp(a) screening, and b) enable the initiation of CV risk management for the prevention of premature ASCVD. Finally, we highlight the importance Lp(a) testing may play in secondary prevention, focusing on cascade screening for elevated Lp(a) in relatives of affected individuals.