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. 2020 Nov:313:111-117.
doi: 10.1016/j.atherosclerosis.2020.09.029. Epub 2020 Oct 4.

Is periodontitis a risk factor for ischaemic stroke, coronary artery disease and subclinical atherosclerosis? A Mendelian randomization study

Steven Bell  1 , Joel T Gibson  2 , Eric L Harshfield  2 , Hugh S Markus  2
Affiliations

Is periodontitis a risk factor for ischaemic stroke, coronary artery disease and subclinical atherosclerosis? A Mendelian randomization study

Steven Bell et al. Atherosclerosis. 2020 Nov.

Abstract

Background and aims: Observational studies have reported an association between periodontitis and cardiovascular disease but whether this association is causal is uncertain. We therefore used Mendelian randomization to test whether periodontitis is causally associated with stroke, coronary artery disease, or subclinical atherosclerosis.

Methods: A two-sample Mendelian randomization analysis was carried out using five single nucleotide polymorphisms previously associated with periodontitis in genome-wide association studies. Summary data were drawn from MEGASTROKE and combined with de novo analyses of UK Biobank for stroke and its major subtypes (up to 44,221 cases, 739,957 controls) and CARDIoGRAMplusC4D and UK Biobank for coronary artery disease (122,733 cases, 424,528 controls). We used existing data on carotid intima-media thickness in UK Biobank as a marker of subclinical atherosclerosis (N = 22,179). Causal estimates were obtained using inverse-variance weighted Mendelian randomization. Sensitivity analyses were performed using weighted median and MR-Egger approaches.

Results: No association was found between periodontitis and any stroke (odds ratio [OR] per doubling in the odds of periodontitis 0.99, 95% confidence interval [CI] 0.97 to 1.02), ischaemic stroke (OR 1.00, 95% CI 0.97 to 1.03) or its major subtypes (p > 0.4), or coronary artery disease (OR 1.01, 95% CI 0.99 to 1.03). Similarly, we found no association for periodontitis and subclinical atherosclerosis (β -0.002, 95% CI -0.004 to 0.001). These results were consistent across a series of sensitivity analyses.

Conclusions: These findings provide no robust evidence for a causal relationship between periodontitis and stroke or coronary artery disease. This suggests that associations reported in observational studies may represent confounding.

Keywords: Carotid intima-media thickness; Coronary artery disease; Inflammation; Mendelian randomization; Periodontitis; Risk factor; Stroke.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Cross-hair plots of genotype-periodontitis and genotype-outcome associations for stroke and coronary artery disease.
Fig. 2
Fig. 2
Causal association estimates for a doubling in the odds of periodontitis with risk of stroke and coronary artery disease obtained from inverse-variance weighted Mendelian randomization. Estimates are shown from analyses using (A) all 5 SNPs and (B) following exclusion of rs1537415. OR (95% CI), odds ratio (95% confidence interval).
See this image and copyright information in PMC

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