Prevalence of hyperhomocysteinemia in South Asian patients with heart disease: a systematic review and meta-analysis

Hyperhomocysteinemia, characterized by an elevated concentration of serum homocysteine, is a well-recognized risk factor for cardiovascular pathophysiology. South Asians are known to have a high burden of cardiovascular disease, and hyperhomocysteinemia is commonly observed in this population. The present systematic review and meta-analysis aimed to assess the pooled prevalence of hyperhomocysteinemia and estimate the serum homocysteine concentrations among South Asians with heart disease. Following PRISMA 2020 reporting guidelines, systematic searches were conducted to identify studies focusing on the South Asians, heart disease and homocysteine. Random-effects meta-analyses were performed using MetaXL to determine the pooled prevalence of hyperhomocysteinemia among patients with heart disease, and standardized mean difference in serum homocysteine concentration between patients with and without heart disease. Meta-regression analyses were performed to identify the source of data heterogeneity. Additionally, GRADE tool was used to assess the certainty of evidence for the study outcomes. A total of 47 articles comprising 6094 heart disease patients from India, Pakistan, Bangladesh and Afghanistan met the inclusion criteria. The overall pooled prevalence of hyperhomocysteinemia was 61% (95% CI: 49–72%) with a significant heterogeneity (I 2 = 98%; p < 0.01). The weighted mean serum homocysteine concentration was 20.98 µmol/L (SD: 4.57). Additionally, the standardized mean difference in serum homocysteine concentration between patients with and without heart disease was 2.22 (95% CI: 1.63–2.82). Subgroup analyses of pooled prevalence and standardized mean difference based on different covariates demonstrated high degree of heterogeneity (I 2 = 85–98%; p < 0.01) and the subsequent meta-regression analyses indicated that study precision, as indicated by the standard error and the number of patients, substantially contributed to the observed heterogeneity. Finally, GRADE assessment rated certainty of evidence for prevalence as low and for SMD as moderate. Despite variability and limited country representation, this first meta-analysis of South Asian population shows that the prevalence of hyperhomocysteinemia is high among heart disease patients in this region, with homocysteine concentrations significantly exceeding the diagnostic threshold of ≥ 15 µmol/L. These findings stress the need for homocysteine-lowering interventional studies to confirm hyperhomocysteinemia as a potential risk factor of heart disease in this region. Prospero registration number: CRD42023424762.