Association between cardiovascular diseases and apical periodontitis: An umbrella review with stratification of evidence and sensitivity analysis

Abstract

Objectives: To systematically evaluate epidemiological evidence regarding cardiovascular disease (CVD) and apical periodontitis (AP) associations through umbrella review methodology.

Data: Ten systematic reviews were synthesized, including five meta-analyses encompassing 1108-673,083 participants. Meta-analytical effect sizes demonstrated relative risks ranging from 1.20 to 1.38, odds ratios of 1.53 to 2.94, with substantial between-study heterogeneity (I² = 54 %-100 %). The pooled estimates of RR studies were 1.32[1.0 to 1.62; p = 0.007] and for Odds ratio 1.83[1.33 to 2.53; P < 0.001]. Evidence stratification revealed significant heterogeneity in effect magnitudes, methodological approaches, and study quality assessments.

Sources: Comprehensive searches of PubMed/MEDLINE, Scopus, EBSCO Host, and multiple grey-literature repositories were conducted from database inception to February 2025, using optimized strategies that integrated Medical Subject Headings, Boolean logic, truncation, and proximity operators.

Study selection: Dual independent reviewer screening identified systematic reviews examining CVD-AP associations. Following duplicate removal and consensus resolution, 10 systematic reviews were included from 7472 initially screened articles.

Conclusion: This umbrella review of ten systematic reviews-including five meta-analyses spanning 1108 to 673,083 participants-demonstrates a consistent, moderately elevated cardiovascular risk associated with apical periodontitis. Pooled estimates showed a 32 % increase in relative risk (RR = 1.32, 95 % CI = 1.00-1.62; p = 0.007) and an 83 % higher odds of cardiovascular disease (OR = 1.83, 95 % CI = 1.33-2.53; p < 0.001). However, substantial between-study heterogeneity (I² = 54 - 100 %) and variability in diagnostic criteria temper causal inference.

Clinical significance: Collectively, the evidence supports AP as an independent, clinically important marker of cardiovascular vulnerability, justifying intensified prevention and management of endodontic infection within cardiometabolic risk reduction strategies. Future large, prospective cohorts employing standardized AP definitions and rigorous confounder control are needed to clarify dose-response patterns and underlying mechanisms.

Keywords: Apical periodontitis; Cardiovascular diseases; Endodontics; Evidence-based dentistry; Meta-analysis; Periapical diseases; Periapical periodontitis; Risk assessment; Systematic review.