Homocysteine is associated with higher risks of ischemic stroke: A systematic review and meta-analysis

BACKGROUND: High levels of homocysteine (Hct) have been associated with great risks of ischemic stroke. However, some controversy still exists. We performed a systematic review and meta-analysis to compare the levels of Hct between patients with ischemic stroke and controls. METHODS: We performed a systematic literature search for articles reporting Hct levels of patients with occurrence of ischemic stroke. We employed a random-effects inverse-variance weighted meta-analytical approach in order to pool standardized mean differences, with estimation of τ(2) through the DerSimonian-Laird method. RESULTS: The initial search yielded 1361 studies. After careful analysis of abstracts and full texts, the meta-analysis included data from 38 studies, which involved almost 16 000 stroke events. However, only 13 studies reported means and standard deviations for cases and controls, and therefore were used in the meta-analysis. Those studies presented data from 5002 patients with stroke and 4945 controls. Standardized mean difference was 1.67 (95% CI 1.00–2.25, P < 0.01), indicating that Hct levels were significantly larger in patients with ischemic stroke compared to controls. Between-study heterogeneity was very large (I(2) = 99%), particularly because three studies showed significantly large mean differences. CONCLUSION: This meta-analysis shows that patients with ischemic stroke have higher levels of Hct compared to controls. Whether this is a modifiable risk factor remains to be assessed through larger prospective cohorts.