“Lipoprotein(a) across coronary plaque phenotypes from high-risk to layered plaque: An OCT analysis from the RELACS registry”

BACKGROUND Lipoprotein(a) [Lp(a)] is a causal risk factor for coronary artery disease, but its relationship with coronary plaque morphology assessed by optical coherence tomography (OCT) remains incompletely characterized. OBJECTIVE To investigate the association between circulating Lp(a) levels and OCT-defined coronary plaque phenotypes using a comprehensive segment-level approach. METHODS In this prospective single-center study (RELACS registry; NCT05496790), consecutive patients undergoing intracoronary OCT with available Lp(a) measurements were included. Coronary vessels were divided into 3 mm segments and analyzed for plaque characteristics. Lp(a) was primarily modeled as a continuous variable to assess its association with OCT-defined plaque phenotypes, including high-risk, layered, and fibrous plaques. High-risk plaque was defined as the presence of ≥2 criteria between lipid-rich plaque, thin-cap fibroatheroma (TCFA), and macrophages. Mixed-effects logistic regression models were used to account for within-patient clustering. RESULTS A total of 952 coronary segments from 50 patients were analyzed. Increasing Lp(a) levels were significantly associated with multiple features of plaque vulnerability, including TCFA, lipid-rich plaques, macrophages, and microchannels. In the multivariate mixed-effects analysis, higher Lp(a) levels were independently associated with a greater likelihood of high-risk plaque (odds ratios [OR] 1.31, 95% CI 1.16-1.48; P < .001) and layered plaques (OR 1.15, 95% CI 1.02-1.29; P = .024), whereas an inverse association was observed with fibrous plaques (OR 0.84, 95% CI 0.70-1.00; P = .047). CONCLUSION Increasing Lp(a) levels were associated with OCT-defined coronary plaque phenotypes related to vulnerability and instability, including high-risk and layered plaques. Given the limited patient-level sample size, these findings should be considered exploratory and hypothesis-generating.