Lipoprotein(a) selectively associates with vulnerable coronary plaque phenotypes in comparison with other established risk markers

AIMS: Lipoprotein(a) [Lp(a)] is an inherited cardiovascular risk factor. However, its association with coronary plaque characteristics beyond traditional risk enhancers remains unclear. We aimed to evaluate the association between Lp(a) levels and coronary plaque characteristics in asymptomatic primary prevention patients, and to compare its predictive value against other risk enhancers, including LDL particle concentration (LDL-P), high-sensitivity C-reactive protein (hsCRP), and coronary artery calcium (CAC) score. METHODS AND RESULTS: We retrospectively analysed 547 asymptomatic patients undergoing coronary computed tomography angiography (CCTA) between 2018 and 2024. Plaque characteristics were assessed using artificial intelligence-based quantitative CCTA. Associations between Lp(a), LDL-P, hsCRP, CAC score, and plaque features were evaluated using multivariable regression adjusted for age and sex. Median age was 56 years, 69.8% were male. Higher Lp(a) was associated with greater total plaque volume (β=23.1 mm³, P = 0.006), calcified plaque (β=11.1 mm³, P = 0.014), non-calcified plaque (β=12.0 mm³, P = 0.027), and low-density non-calcified plaque (LDNCP; β=0.4 mm³, P < 0.001) volumes, as well as increased area stenosis (β=1.9%, P = 0.031) and remodelling index (β=0.02, P = 0.017). In multivariable models, CAC score was the strongest predictor of overall plaque burden, including calcified and non-calcified plaque (P < 0.000), but was not associated with LDNCP. Lp(a) remained independently associated with LDNCP (β=0.45 mm³, P = 0.013), while LDL-P and hsCRP showed no significant associations. CONCLUSION: In asymptomatic primary prevention patients, Lp(a) was independently associated with high-risk coronary plaque features, specifically LDNCP, beyond traditional risk enhancers. These findings highlight the unique role of Lp(a) in identifying coronary plaque vulnerability and suggest complementary roles for Lp(a) and CAC in refining cardiovascular risk stratification.