Plasma homocysteine and cardiovascular outcomes in postmenopausal women with coronary heart disease: a retrospective cohort study

Abstract Background The association between plasma homocysteine (Hcy) and adverse cardiovascular outcomes in postmenopausal women with coronary heart disease (CHD) remains unclear. This study aimed to investigate the prognostic value of Hcy levels in this high-risk population. Methods We conducted a retrospective cohort study of 624 postmenopausal women with CHD from Ningxia Medical University General Hospital, with a 3-years follow-up. The association between Hcy and major adverse cardiovascular events (MACE) was evaluated using multivariate Cox regression. Non-linear relationships were assessed using generalized additive models (GAM) and threshold effect analyses. Survival disparities were analyzed via Kaplan-Meier estimates. Stratified analyses assessed association robustness, and receiver operating characteristic (ROC) curve analysis determined the predictive capacity of Hcy for MACE risk. Results During follow-up, 133 MACE occurred. Higher Hcy tertiles were associated with increased cumulative MACE risk (log-rank, P  < 0.001). The multivariable cox regression revealed a significant positive relationship between Hcy and MACE risk. After full adjustment, each 1 µmol/L increment in Hcy was associated with an 16% increased risk of MACE (HR 1.16, 95% CI 1.12–1.22; P  < 0.0001). GAM analyses uncovered non-linear relationships ( P for non-linearity < 0.05). Threshold analysis identified an inflection point at 15.78 µmol/L. Subgroup analyses confirmed the robustness of this association (all P interaction > 0.05). ROC curve analysis demonstrated moderate predictive accuracy for Hcy (AUC 0.729, 95% CI 0.682–0.777), with an optimal risk-stratification cutoff at 19.72 µmol/L. Conclusion Hcy may be independently associated with MACE in postmenopausal women with CHD. Hcy may serve as a valid predictor of MACE in this patient population.