Use of smokeless tobacco and risk of cardiovascular disease: A systematic review and meta-analysis.

Objective The purpose of this study was to assess the risk of ischaemic heart disease (IHD) and stroke (non-fatal and fatal) among adult ever-users of smokeless tobacco (ST). Design The study design involved a systematic review and meta-analysis of observational studies. Methods Data sources for the review included key electronic databases and reference lists. Studies were included based on design (cohort or case-control), exposure (exclusive use of ST or adjusted for smoking), and outcome (non-fatal and fatal IHD and stroke). Data extraction included reported measures of association (risk ratios (RRs) or odds ratios (ORs)) between ever-use of ST (current or past) and cardiovascular disease (CVD) outcomes among non-smokers, and other study characteristics. The Newcastle-Ottawa scale was used to assess study quality. Summary measures were estimated using random effects models. Results Twenty studies were included in the meta-analyses. Overall, significantly increased risk of IHD deaths (1.15, 95% confidence interval (CI: 1.01-1.30) and stroke deaths (1.39, 95% CI: 1.29-1.49) was found among ever-users of ST. We did not find an overall significant increased risk for IHD (1.14, 95% CI: 0.92-1.42) or stroke (1.01, 95% CI: 0.90-1.13). But geographical variations were marked for IHD, with significant positive association in Asian studies (1.40, 95% CI: 1.01-1.95), and the INTERHEART study, where ST data was mainly reported from Asia (2.23, 95% CI: 1.41-3.53). European studies did not show an increased risk for non-fatal CVD. Conclusion An association was found between ever use of ST and risk of fatal IHD and stroke, consistent with previous reviews. ST consumption also appears to significantly increase risk of non-fatal IHD among users in Asia, but not in Europe.