Abstract
OBJECTIVES: To evaluate whether periodontitis is associated with stroke and to update pooled estimates with recent studies. METHODS: We systematically searched Medline, Embase, and the Cochrane Database of Systematic Reviews from inception to July 2025. We included cohort and case-control studies of adults comparing periodontitis with no periodontitis and reporting any stroke (ischemic, hemorrhagic, or unspecified). Random-effects models were used. Case-control and cohort data were pooled separately. Prespecified subgroups included stroke subtype, study design, sex, and follow-up duration. Publication bias was assessed when ≥10 studies were available. RESULTS: Twenty-two studies were included (16 cohorts; 6 case-control). In case-control studies, periodontitis was associated with higher odds of stroke (OR, 2.22; 95% CI, 1.48-3.34; I (2) = 33%). In cohorts, periodontitis was associated with increased incident stroke risk (RR, 1.49; 95% CI, 1.23-1.80; I (2) = 96%). In subgroup analysis, prospective cohorts showed slightly higher and more stable estimates than retrospective cohorts (RR, 1.53 vs. 1.40; I (2) = 61% vs. 98%). Studies with >10 years of follow-up showed a stronger, less heterogeneous association (RR, 1.57; 95% CI, 1.35-1.84; I (2) = 32%). Funnel plots suggested limited publication bias. CONCLUSIONS: Periodontitis is associated with increased stroke risk, most clearly for ischemic outcomes and in long-term prospective cohorts. Given high heterogeneity and potential residual confounding, the findings support association rather than causation. Standardized periodontal definitions, subtype-specific endpoints, and rigorous prospective and interventional studies are needed to test clinical impact.