Lipoprotein(a) Distribution and Cardiovascular Risk in Japan: Insights from a Multi-center LEAP Study

Abstract

Aim: Although lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for cardiovascular disease (CVD), its distribution and risk thresholds in the Japanese population remain unclear. This study aimed to characterize the distribution of Lp(a) in Japanese clinical settings and evaluate its association with CVD risk, including coronary artery disease (CAD), atherosclerotic cardiovascular disease (ASCVD), and familial hypercholesterolemia (FH).

Methods: The LEAP study is a multicenter retrospective cohort analysis of 6,173 patients from six Japanese institutions. The Lp(a) values were harmonized to nmol/L using kit-specific conversion equations, enabling a consistent analysis across different immunoassays. Associations with CAD, ASCVD, chronic kidney disease (CKD), diabetes mellitus (DM), and FH were assessed. The risk thresholds were defined using a receiver operating characteristic analysis.

Results: The median Lp(a) concentration was 20.88 nmol/L, with a right-skewed distribution. Elevated Lp(a) levels were significantly associated with CAD, ASCVD, CKD, and FH. In contrast, DM was related to lower Lp(a). An ROC analysis identified 25 nmol/L as a screening threshold and 125 nmol/L as a high-risk boundary. The CAD prevalence increased stepwise across these categories: 20.2% (≤ 25 nmol/L), 30.3% (25–125 nmol/L), and 39.9% (＞125 nmol/L).

Conclusion: This study provides the first nmol/L-standardized Lp(a) distribution in Japanese patients and proposes provisional thresholds for clinical risk stratification.