Periodontitis and the Risk of Heart Failure:a Meta-analysis and Mendelian Randomisation Study

Abstract

Purpose: Periodontitis and heart failure (HF) impact millions of individuals globally with heavy social and economic burden. Prior research has indicated a connection between them. However, the conclusions have been somewhat inconsistent. Our objective is to confirm, through meta-analysis and Mendelian randomisation studies, whether patients with periodontitis have an increased risk of HF. Therefore, we conducted a comprehensive analysis to explore the causal association between periodontitis and the risk of HF.

Materials and methods: In this meta-analysis, we searched online to identify studies involving periodontitis on the risk of HF. The main endpoint assessed in this study was the risk of HF. We used R language to calculate the pooled results and create plots. A random-effects model was employed in the analyses. In the Mendelian randomisation (MR) analyses, we obtained data from public databases. MR analyses were conducted using genome-wide association data for acute and chronic periodontitis. Independent genetic variants associated significantly with each exposure (P 5*10-6) were considered as instruments. The primary analysis employed the inverse variance weighted (IVW) method, which was subsequently supplemented by a series of sensitivity analyses to ensure the robustness and reliability of the findings.

Results: Our meta-analysis included three publications, with a total of 21,997 participants. The pooled result demonstrated that periodontitis increased the risk of HF (OR = 1.62, 95% CI 1.29-2.03). Periodontitis increased the risk of heart failure with reduced ejection fraction (HFrEF) with a low level of heterogeneity (OR = 1.99, 95% CI 1.22-3.23) and heart failure with preserved ejection fraction (HFpEF) with little heterogeneity (OR = 1.36, 95% CI 1.00-1.86). In the MR study, acute or chronic periodontitis did not increase the risk of HF. Sensitivity analyses revealed that the causal association estimations were robust.

Conclusion: In summary, the meta-analysis results indicate that individuals with periodontitis are at a higher risk of HF. The findings from the MR study fail to establish a causal link between the two variables under investigation. To validate this assertion and elucidate the fundamental mechanism, additional research is imperative.

Clinical significance: Based on the current evidence, it cannot be concluded that there is a causal relationship between acute or chronic periodontitis and HF.

Keywords: Mendelian randomisation study; causal relationship; heart failure; meta-analysis; periodontitis; systematic review.

Fig 1

Study flow diagram.

Fig 2

Periodontitis increased the risk of HF.

Fig 3

Periodontitis increased the risk of HFrEF.

Fig 4

Periodontitis increased the risk of HFpEF without statistical significance.

Fig 5

Causal effects of periodontitis on the risk of heart failure.

Fig 6

Causal effects of acute periodontitis on the risk of heart failure per allele from the data source of UK biobank.

Fig 7

Causal effects of acute periodontitis on the risk of heart failure per allele from the data source of FinnGen.

Fig 8

Causal effects of chronic periodontitis on the risk of heart failure per allele from the data source of UK biobank.

Fig 9

Causal effects of chronic periodontitis on the risk of heart failure per allele from the data source of FinnGen.

Fig 10

Scatter plot for MR analysis of acute periodontitis on heart failure from the database of UK biobank.

Fig 11

Scatter plot for MR analysis of acute periodontitis on heart failure from the database of FinGen.

Fig 12

Scatter plot for MR analysis of chronic periodontitis on heart failure from the database of UK biobank.

Fig 13

Scatter plot for MR analysis of chronic periodontitis on heart failure from the database of FinGen.

Fig 14

Forest plot for leave-one-out analysis of acute periodontitis on heart failure from the database of UK biobank.

Fig 15

Forest plot for leave-one-out analysis of acute periodontitis on heart failure from the database of FinGen.

Fig 16

Forest plot for leave-one-out analysis of chronic periodontitis on heart failure from the database of UK biobank.

Fig 17

Forest plot for leave-one-out analysis of chronic periodontitis on heart failure from the database of FinGen.

Fig 18

Funnel plot for MR analysis of acute periodontitis on heart failure from the database of UK biobank.

Fig S19

Funnel plot for MR analysis of acute periodontitis on heart failure from the database of FinGen.

Fig S20

Funnel plot for MR analysis of chronic periodontitis on heart failure from the database of UK biobank.

Fig S21

Funnel plot for MR analysis of chronic periodontitis on heart failure from the database of FinGen.