Association of homocysteine level with risk of stroke: A dose-response meta-analysis of prospective cohort studies

Background and aims: Homocysteine (Hcy) level has been increasingly linked with stroke and ischemic stroke (IS). However, a dose-response meta-analysis of prospective cohort studies of the association is lacking. We aimed to explore the quantitative dose-response association of Hcy level with stroke and IS in a meta-analysis of prospective cohort studies. Methods and results: We performed a systematic search of PubMed, Embase and Web of Science databases up to April 25, 2019 for prospective cohort studies assessing the association of Hcy level with stroke and IS. We used random-effect models to estimate the pooled relative risk (RRs) (with 95% confidence intervals [CIs]) for the association of Hcy with risk of stroke and IS. Restricted cubic splines were used to evaluate possible linear or nonlinear association of Hcy level with stroke and IS. We included 10 prospective cohort studies (7 articles) with 11,061 participants in the meta-analysis. Hcy level was associated with increased risk of stroke (RR = 1.58, 95% CI 1.25-2.00, I-2 = 39.5%) and IS (RR = 1.54, 95% CI 1.21-1.97, I-2 = 36.4%) for the highest versus the lowest categories. We found a linear association between Hcy level and stroke (P-nonlinearity = 0.660) and IS (P-nonlinearity = 0.981). For each 1-mmol/L increase in Hcy, the pooled RR was 1.06 (95% CI 1.01-1.12, I-2 = 59.0%) for stroke and 1.05 (95% CI 1.00-1.11, I-2 = 58.6%) for IS. Conclusion: This meta-analysis indicated that elevated Hcy level was associated with increased risk of stroke and IS. (C) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.