Abstract 4363265: Lipoprotein(a) Selectively Associates with Vulnerable Coronary Plaque Phenotypes in Comparison with Other Established Risk Markers

Background: Lipoprotein(a) [Lp(a)] is associated with increased cardiovascular risk; however, its contribution to coronary plaque burden and composition, compared to traditional risk enhancers, remains incompletely defined. Objectives: Investigate associations between Lp(a) levels and coronary plaque characteristics in asymptomatic patients, and to compare its predictive value against other cardiovascular disease (CVD) risk enhancers, including LDL particle concentration (LDL-P), high-sensitivity C-reactive protein (hsCRP), and coronary artery calcium (CAC) score. Methods: Retrospective study of asymptomatic patients undergoing coronary computed tomography angiography (CCTA) for primary prevention between 2018–2024. Plaque characteristics were assessed using artificial intelligence-based quantitative CCTA (AI-QCT). Associations between standardized Lp(a), LDL-P, CAC score, hsCRP and plaque volumes were evaluated using linear regression models adjusted for age and sex. Results: The cohort included 547 patients (median age 56 years old, 70% male, 50% on statin therapy). In linear regression analyses adjusted for age and sex, higher Lp(a) levels (per 1 SD increase) were significantly associated with greater total plaque volume (β=23.11 mm 3 , p=0.006), calcified plaque (β=11.13 mm 3 , p=0.014), non-calcified plaque (β=11.99 mm 3 , p=0.027), low-density non-calcified plaque (LDNCP) (β=0.43 mm 3 , p<0.001; Figure 1), maximum diameter stenosis (β=1.37%, p=0.027), area stenosis (β=1.91%, p=0.031), and remodeling index (β=0.02, p=0.017). In a multivariable model, comparing the different CVD risk enhancers, CAC score remained the strongest predictor of total plaque, calcified plaque, and non-calcified plaque volumes (p < 0.0001 for all). However, CAC score was not associated with LDNCP. Elevated Lp(a) levels were independently associated with LDNCP (β=0.45 mm 3 , p=0.013), even after adjustment for LDL-P, hsCRP, and CAC. Neither LDL-P nor hsCRP were significantly associated with any plaque subtype in the multivariable analysis (Table 1). Conclusions: In asymptomatic primary prevention patients, Lp(a) was independently associated with high-risk coronary plaque features, specifically LDNCP, beyond traditional risk enhancers.