Association Between Smokeless Tobacco Use and Cardiovascular Disease Outcomes: A Systematic Review and Meta-Analysis With Subgroup Evaluation of Nawar-Type Products

Background: Smokeless tobacco (SLT) use remains prevalent globally and is associated with cardiovascular disease (CVD). However, variations in product composition, particularly between Scandinavian snus and alkaline, unfermented preparations such as Nawar, may influence risk profiles. Methods: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from January 1990 to December 2024 (final search: December 15, 2024). Observational studies evaluating SLT use and CVD outcomes in adults were included. Sixteen studies met the inclusion criteria, including 14 primary studies and 2 prior meta-analyses. Random-effects models were used to compute pooled odds ratios (ORs). Primary outcomes included composite CVD events (fatal and non-fatal), myocardial infarction (MI), stroke, and CVD mortality. Results: SLT use was associated with increased CVD risk (pooled OR: 1.45; 95% CI: 1.28-1.64; I² = 47%). Elevated risks were observed for MI (OR: 1.42; 95% CI: 1.21-1.67) and composite CVD outcomes (OR: 1.61; 95% CI: 1.32-1.96). Subgroup analyses showed higher estimates in South and Central Asia (OR: 1.83), though these were based on a limited number of studies. Nawar-type products were represented in a small subset of studies, and their contribution to the pooled estimate was limited relative to mixed SLT and Scandinavian snus cohorts. Sensitivity analyses excluding prior meta-analyses yielded consistent but slightly attenuated estimates. Conclusions: SLT use is associated with a statistically significant increase in CVD risk. While Nawar-type products may confer a higher risk, evidence remains limited and predominantly derived from cross-sectional studies. Large prospective studies in high-prevalence regions are required to clarify product-specific effects.