Association between homocysteine and coronary artery disease—trend over time and across the regions: a systematic review and meta-analysis

Background The association of homocysteine with coronary artery disease (CAD) has been explored previously with mixed findings. The present Systematic Review and Meta-Analysis (SRMA) has assessed the pooled estimate of association between homocysteine (Hcy) and CAD, and its variation over the period and geography. Methods Systematic literature search was done in PubMed, Scopus and Cochrane to identify the observational studies that have reported mean Hcy among cases (CAD) and control. The SRMA was registered in PROSPERO (ID-CRD42023387675) . Results Pooled standardized mean difference (SMD) of Hcy levels between the cases and controls was 0.73 (95% CI 0.55–0.91) from 59 studies. Heterogeneity was high (I 2 94%). The highest SMD was found among the Asian studies (0.85 [95% CI 0.60–1.10]), while the European studies reported the lowest SMD between the cases and controls (0.32 [95% CI 0.18–0.46]). Meta-regression revealed that the strength of association was increasing over the years (Beta = 0.0227, p = 0.048). Conclusions Higher homocysteine levels might have a significant association with coronary artery diseases, but the certainty of evidence was rated low, owing to the observational nature of the studies, high heterogeneity, and publication bias. Within the population groups, Asian and African populations showed a greater strength of association than their European and American counterparts, and it also increased over the years.