Association of Lipoprotein(a) With Coronary Atherosclerosis and Cardiovascular Events

BACKGROUND: High lipoprotein(a) (Lp[a]) associates with elevated coronary heart disease event risk, but it remains uncertain whether this excess risk can be explained by increased coronary plaque burden. OBJECTIVES: This study aims to determine whether Lp(a)-related excess cardiovascular risk in the general population is primarily explained by increased coronary atherosclerosis or by additional plaque vulnerability-related effects. METHODS: This study included 28,529 middle-aged individuals from the SCAPIS (Swedish CArdioPulmonary bioImage Study), a population-based cohort. Coronary atherosclerosis was assessed using coronary computed tomography angiography in 25,916 participants. Incident coronary events, defined as fatal or nonfatal myocardial infarction, were ascertained over a median follow-up of 7.8 years. RESULTS: High Lp(a) was present in 14% of participants and associated with severe/extensive coronary atherosclerosis (Segment Involvement Score >4; OR: 1.38; 95% CI: 1.21-1.57) and coronary events (HR: 1.54; 95% CI: 1.18-2.0). Stratified, adjusted, and mediation analyses consistently suggested that the association between Lp(a) and coronary event risk is largely explained by greater atherosclerotic burden (P for mediation