Does lipoprotein(a) associate with coronary high-risk plaque in patients without hypercholesterolemia? Insights from optical coherence tomography imaging

Background Lipoprotein(a) (Lp(a)) increased the risk of cardiovascular events and atherosclerotic disease. More than 10% of the population has isolated lipoprotein(a) elevation in the absence of hypercholesterolemia. Purpose This study aimed to investigate the coronary plaque features in patients with isolated lipoprotein(a) elevation by using optical coherence tomography (OCT) imaging. Methods This single-center, observational study included 827 patients with acute coronary syndrome and without hypercholesterolemia who underwent OCT imaging during coronary intervention. Baseline serum samples were obtained and the level of lipoprotein(a) was measured. Patients were divided into the elevated Lp(a) group (Lp(a) ≥75nmol/L, n=124, 15.0%) and the normal Lp(a) group (Lp(a) <75nmol/L, n=703, 85.0%). Coronary plaque features were analyzed by using OCT. Results The average age of all patients was 57.6±10.7 years, with 74.1% of male. A total of 827 culprit lesions and 3285 non-culprit lesions were measured. In culprit lesion, the prevalence of plaque rupture (60.5% vs. 50.1%, P=0.032) and thin-cap fibroatheroma (TCFA, 59.7% vs. 46.2%, P=0.006) was significantly higher in the elevated Lp(a) group than the normal Lp(a) group. The elevated Lp(a) group also had thinner fibrous cap (56.7 [40.0, 76.7]μm vs. 61.6 [46.7, 90.8]μm, P=0.013). As for non-culprit segments, patients with elevated Lp(a) levels had more prevalent TCFA (38.7% vs. 26.3%, P=0.005). Similar findings were also found at the lesion-level analyses. Non-culprit lesions in the elevated Lp(a) group presented with a higher incidence of TCFA (13.5% vs. 9.7%, P=0.022), and they also had a smaller minimal lumen area (3.9 [2.5, 5.3]mm2 vs. 4.0 [2.6, 5.9] mm2, P=0.015) and thinner fibrous cap (95.0[70.0,123.3]μm vs. 100.0 [73.3,136.7]μm, P=0.025). Multivariate analysis showed Lp(a) ≥75nmol/L was independently associated with culprit TCFA (adjusted odds ratio [95%CI]: 1.87 [1.19 - 2.93], P=0.006) and non-culprit TCFA (adjusted OR [95%CI]: 1.91 [1.19- 3.05], P=0.005). Conclusion In patients with acute coronary syndrome and without hypercholesterolemia, elevated lipoprotein(a) levels are independently associated with a higher prevalence of high-risk coronary plaques in both culprit and non-culprit lesions. These findings highlight the prognostic value of Lp(a) for identifying vulnerable coronary plaque even in the absence of elevated LDL-C or hypercholesterolemia, supporting the role of Lp(a) as an independent risk marker for coronary vulnerability in this population.