Elevated lipoprotein(a) is a known genetic risk factor for cardiovascular disease, but its role in coronary plaque progression is less understood. ESC 2025 analysis assessed 157 patients with acute coronary syndrome who underwent optical coherence tomography of non-culprit lesions at baseline and 12-month follow-up. Patients were divided into normal Lp(a) (<75 nmol/L) and elevated Lp(a) (≥75 nmol/L) groups.

At follow-up, patients with normal Lp(a) demonstrated plaque stabilization, with decreased prevalence of thin-cap fibroatheroma and reduced lipid arc. Conversely, patients with elevated Lp(a) experienced increased thin-cap fibroatheroma (26.7% vs 42.2%, P=0.004) and macrophage accumulation (92.2% vs 97.8%, P=0.046). Notably, 27.8% of non-culprit lesions in the elevated Lp(a) group developed new thin-cap fibroatheroma compared with 10.1% in the normal group. Multivariate analysis confirmed elevated Lp(a) as an independent predictor of newly occurring vulnerable plaques (odds ratio 3.42, 95% CI 1.78–6.56, P<0.001).

These findings highlight the critical role of Lp(a) in plaque instability and underscore the need for targeted strategies to manage Lp(a)-mediated cardiovascular risk.