Epidemiology
Lp(a) shows a U-shaped, not linear, relationship with MACE in 1,504 three-vessel disease ACS patients (Sci Rep 2025)
Original title: The nonlinear association between lipoprotein(a) and major adverse cardiovascular events in acute coronary syndrome patients with three-vessel disease
In 1,504 patients with acute coronary syndrome and angiographically confirmed three-vessel disease, followed for a median 38 months, higher Lp(a) was independently associated with major adverse cardiovascular events (MACE) on multivariate Cox regression (P < 0.05) after adjustment for confounders, and the association held across subgroups including patients aged 60 years or older, men, and those with hypertension or chronic kidney disease. Lp(a) had modest but significant predictive value for MACE (AUC 0.623, 95% CI 0.593-0.653, P < 0.001). Restricted cubic spline analysis on log-transformed Lp(a) revealed an approximately U-shaped, nonlinear relationship with MACE risk (P nonlinear < 0.001), rather than the simple linear dose-response often assumed. In this high-risk ACS subgroup, both very low and very high Lp(a) may carry excess risk, a pattern worth accounting for in future risk models.
Original abstract
Lipoprotein(a) [Lp(a)] is a lipoprotein with potent atherogenic and thrombogenic potential. Its role in patients with acute coronary syndrome (ACS) combined with three-vessel disease (TVD) remains unclear. This study aimed to investigate the correlation between Lp(a) levels and the occurrence of major adverse cardiovascular events (MACE) in patients with ACS combined with TVD. Patients who underwent coronary angiography and were diagnosed with ACS combined with TVD were selected for the study. Patients were divided into three groups based on their Lp(a) levels. The correlation between Lp(a) and MACE was evaluated using univariate and multivariate Cox regression analysis, subgroup analysis, sensitivity analysis, Kaplan-Meier survival curve, receiver operating characteristic curve (ROC), and restricted cubic spline plot (RCS). A total of 1504 patients were included, with a median follow-up time of 38 months. Univariate Cox regression analysis showed that patients with higher Lp(a) levels had a significantly increased incidence of MACE (P < 0.001). After adjusting for confounding factors, multivariate Cox regression analysis indicated that high Lp(a) levels remained an independent predictor of MACE (P < 0.05). Subgroup analysis revealed that higher Lp(a) levels were significantly associated with a higher risk of MACE in subgroups including patients aged ≥ 60 years, males, those with hypertension, CKD, without diabetes, without hyperlipidemia, and without stroke (P < 0.05). Sensitivity analysis further confirmed the close correlation between Lp(a) and MACE (P < 0.05). Kaplan-Meier survival curve showed that the cumulative incidence of MACE in the high Lp(a) group was significantly higher than in the low-level group (P < 0.001). The ROC curve analysis indicated that Lp(a) had some predictive value for the occurrence of MACE (AUC: 0.623, 95% CI: 0.593-0.653, P < 0.001). The RCS plot demonstrated that after transforming Lp(a) to a normal distribution as Log10Lp(a), there was an approximately U-shaped nonlinear association between Log10Lp(a) and the risk of MACE (P nonlinear < 0.001). Lp(a) levels were significantly associated with the risk of MACE in patients with ACS combined with TVD.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.