Combined Effect of Low-Density Lipoprotein Cholesterol and Homocysteine on Major Adverse Cardiovascular Events in Coronary Heart Disease: A Retrospective Cohort Study

Background: Residual cardiovascular risk remains substantial despite aggressive low-density lipoprotein cholesterol (LDL-C) lowering in coronary heart disease (CHD). Consequently, this elevated risk has spurred the search for non-lipid targets, such as homocysteine (HCY). However, the combined effect of HCY with LDL-C and the overall potential for combined risk stratification remain unclear. Methods: This retrospective cohort study included patients with CHD confirmed by coronary angiography or computed tomography angiography at the General Hospital of Ningxia Medical University between January 2019 and December 2021. Participants were stratified by baseline LDL-C levels (<1.8 vs. ≥1.8 mmol/L) and HCY (<15 vs. ≥15 μmol/L). Major adverse cardiovascular events (MACEs) were employed as the primary endpoint, defined as a composite of all-cause death, stroke, non-fatal myocardial infarction, or unplanned revascularization. Results: A total of 744 MACEs were recorded during the 25-month follow-up. Elevated levels of LDL-C (adjusted hazard ratio (aHR) = 1.38, 95% confidence interval (CI): 1.09–1.73) and HCY (aHR = 1.47, 95% CI: 1.19–1.81) were independently associated with a higher risk of MACEs. The risk was synergistic when both factors were elevated, as patients in the high LDL-C and high HCY group had a significantly increased risk (aHR = 1.97, 95% CI: 1.34–2.90) compared to the reference group with low levels. Conclusion: LDL-C and HCY are independent predictors of MACEs in patients with CHD, and the combined use of these indices improves risk stratification. Thus, integrating these indices into clinical practice could improve personalized management strategies and outcomes in this high-risk population.