The impact of lipoprotein(a) on coronary atherosclerotic plaque phenotype in primary prevention

AIMS: Lipoprotein(a) (Lp[a]) is a causal risk factor for cardiovascular events. However, the effect of Lp(a) on coronary plaque composition and high-risk plaque (HRP) features has not been fully characterized. This study aimed to investigate the association between Lp(a) and coronary atherosclerotic plaque phenotype at the plaque level. METHODS: This study included 710 patients who underwent coronary computed tomography angiography (CCTA) and had Lp(a) measured between 2008 and 2024. CCTA scans were analyzed with a previously validated artificial intelligence-based algorithm (AI-QCT, Cleerly Inc.). The association of Lp(a) with noncalcified and calcified plaque volumes and HRP features was evaluated at the plaque level using generalized estimating equation models adjusted for traditional cardiovascular risk factors. RESULTS: Among the 710 patients, the mean age was 56±10 years and 379 (53%) were male. In total, 3642 plaques were identified. In the adjusted plaque-level analysis, elevated Lp(a) (≥150 nmol/L) was associated with an increase in noncalcified plaque volume per plaque (P=0.009), but not with an increase in calcified plaque volume (P=0.81). Furthermore, elevated Lp(a) (≥150 nmol/L) was strongly associated with the presence of HRP at the plaque level (adjusted odds ratio: 1.78, 95% CI: 1.25-2.54, P=0.001), whereas low-density lipoprotein-cholesterol and high-sensitivity C-reactive protein were not (P>0.05). CONCLUSION: In this plaque-level CCTA study of 3642 individual plaques, elevated Lp(a) levels were independently associated with increased noncalcified plaque volume and with the presence of HRP, but not with calcified plaque volume. These findings elucidate the impact of Lp(a) on unstable plaque phenotypes, even in patients without prior cardiovascular events.