Objective:To assess whether people who ever use any form of chewing substance in Asia are at increased risk of cardiovascular disease(CVD).Methods:PubMed and ISI Web of Science were searched for relevant studies,with no limitation on language or study year.Studies were included if they provided quantitative estimate of the association between ever use of chewing substance and the occurrence of CVD.Two authors independently implemented inclusion criteria,abstracted study characteristics,and performed meta-analysis.Summary relative risks were estimated on the basis of a random effect model.We used Q statistic and Egger’s test to examine heterogeneity across studies and potential publication bias,respectively.Results:Eight eligible studies were included.The relative risk of CVD for ever using chewing substances with or without tobacco was 1.26(95% confidence interval(CI) 1.12-1.40),which was unchanged when restricted to cohort studies [1.25(1.08-1.42)] or cohort studies in Taiwan [1.31(1.12-1.51)].The summary relative risk for ischemic heart disease was 1.27(1.02-1.52),and was lowered to 1.26(0.85-1.67) after exclusion of a cross-sectional study.The overall relative risk for cerebrovascular disease was 1.32(1.08-1.56).On the basis of the Taiwan data,the summary relative risk of CVD for betel(Areca catechu) chewing was 1.30(1.17-1.44).Data on dose-response were limited to betel chewing in Taiwan,suggesting a relationship between risk of CVD and cumulative exposure.Two large cohorts in Taiwan reported a greater risk of CVD with betel chewing than with smoking.Conclusions:An association was detected between betel chewing with or without tobacco and the risk of CVD.Betel chewing may impose a greater CVD risk than smoking.More effort is needed in developing betel chewing cessation programmes.The relationship between betel chewing and subgroups of CVD requires further investigation. Objective: To assess whether people who ever use any form of chewing substance in Asia are at increased risk of cardiovascular disease (CVD). Methods: PubMed and ISI Web of Science were searched for relevant studies, with no limitation on language or study year. Studies were included if they provide quantitative estimate of the association between ever use of chewing substance and the occurrence of CVD.Two authors independently implemented inclusion criteria, abstracted study characteristics, and performed meta-analysis. Summary relative risks were estimated on the basis of a random effect model. We used Q statistic and Egger’s test to examine heterogeneity across studies and potential publication bias, respectively. Results: Eight available studies were included. The relative risk of CVD for ever using chewing substances with or without tobacco was 1.26 (95% confidence interval (CI) 1.12-1.40), which was unchanged when restricted to cohort studies [1.25 (1.08-1.42)] or cohort studies in Taiwan [1.31 (1. The summary relative risk for ischemic heart disease was 1.27 (1.02-1.52), and was lowered to 1.26 (0.85-1.67) after exclusion of a cross-sectional study. The overall relative risk for cerebrovascular disease was 1.32 (1.08-1.56). On the basis of the Taiwan data, the summary relative risk of CVD for betel (Areca catechu) chewing was 1.30 (1.17-1.44). Data on dose-response were limited to betel chewing in Taiwan, suggesting a relationship between risk of CVD and cumulative exposure. Two large cohorts in Taiwan reported a greater risk of CVD with betel chewing than with smoking. Confclusions: An association was detected between betel chewing with or without tobacco and the risk of CVD. Betel chewing may impose a greater CVD risk than smoking. More effort is needed in developing betel chewing cessation programs. The relationship between betel chewing and subgroups of CVD requires further investigation.