O tratamento endodôntico modifica os níveis séricos de marcadores inflamatórios de risco cardiovascular em indivíduos com periodontite apical assintomática? uma revisão sistemática e meta-análise

Abstract

Introduction: Cardiovascular diseases, the leading global cause of death, are associated with asymptomatic apical periodontitis, which plays a contributing role in the onset of chronic low grade systemic inflammation, potentially impacting the overall health of the individual. Chronic low-grade systemic inflammation involves increased blood levels of inflammatory markers, which play a role in the origin and development of cardiovascular alterations, becoming useful in predicting cardiovascular risk. However, there is no consensus on whether these markers—such as inflammatory cytokines [Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6)], cell adhesion molecules [Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1)], and C-reactive protein (CRP)—are reduced with endodontic treatment. This study aimed to summarize the available evidence on the effect of endodontic treatment on serum levels of inflammatory markers associated with cardiovascular risk. Methods. This systematic review and meta-analysis followed PRISMA guidelines and were registered in PROSPERO under the number CRD42023391374. Observational studies including cohorts and case-controls, as well as experimental studies including controlled clinical trials and before-and after, with asymptomatic apical periodontitis patients, were included, without restrictions on age, race, gender, or socioeconomic status. Excluded were cross-sectional studies, case reports, expert opinions, technical reports, editorials, reviews, studies not measuring inflammatory markers in serum before and after endodontic treatment, studies involving acute endodontic conditions, and patients with comorbidities or without control of behavioral risk factor exposures. A systematic search was conducted in PubMed/Medline, Embase, Web of Science, Scopus, BVS (Medline, IBECS, BBO, LILACS), and grey literature sources, with no language or publication date restrictions, in October and November 2022. After removing duplicates, two independent reviewers assessed titles and abstracts. Eligible studies were read in full. Data extraction was performed by two independent reviewers, as well as risk assessment using the Newcastle-Ottawa Scale (NOS) adapted for intervention studies. Additionally, the quality of evidence and strength of recommendation was assessed using the GRADE system (Grading of Recommendations Assessment, Development, and Evaluation). Discrepancies were resolved by consensus or third party adjudication. Random-effects meta-analyses with DerSimonian and Laird estimator were conducted to estimate pooled mean differences (MD) and 95% confidence intervals (CI) of inflammatory marker concentrations between groups undergoing endodontic treatment and controls. Subgroup analyses were conducted to investigate differences in estimates between studies with and without their control group, using an external control group. Heterogeneity among studies was assessed using Cochran's Q test and I2. Due to the limited number of studies, publication bias analyses were not feasible. All analyses were performed using Stata version 14.0, considering alpha=5%. Results: A total of 2,101 publications were identified. After removing duplicates and evaluating titles and abstracts, 12 studies were eligible. After full-text reading, five studies evaluating serum levels of inflammatory markers before and after endodontic treatment, compared to healthy controls, were included in the systematic review and meta-analysis. Various inflammatory markers were analyzed, including CRP, IL-6, TNF-α, VCAM-1, and ICAM-1. Based on NOS, all studies showed a moderate risk of bias. The evidence level, according to GRADE, was considered very low for all evaluated outcomes. Meta-analysis results indicated that endodontic treatment possibly reduced serum levels of CRP [MD=0.50 (95% CI: -0.64, 1.65)] and VCAM-1 [MD=0.03 (95% CI: -0.15, 0.21)] to values similar to controls, but did not affect IL-6 [MD=6.26 (95% CI: 4.26, 7.87)], TNF-α [MD=7.26 (95% CI: 3.61, 10.91)], and ICAM-1 [MD= 44102.04 (95% CI: -122551.39, 34347.32)]. Heterogeneity among studies was observed in most meta-analyses (I2>50% and P<0.10), even in subgroup analyses. Conclusion: Available evidence suggests the possibility that endodontic treatment may reduce serum levels of CRP and VCAM 1. However, with few studies, a risk of bias, and a very low evidence level, confidence in the effect estimate is limited, indicating a significant degree of uncertainty in these findings.