Abstract
Observational studies have revealed that dental diseases such as periodontitis and dental caries increase the risk of cardiovascular diseases (CVDs). However, the causality between periodontal disease (PD) and CVDs is still not clarified. In the present study, two-sample Mendelian randomization (MR) studies were carried out to assess the association between genetic liability for periodontal diseases (dental caries and periodontitis) and major CVDs, including coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), and stroke—including ischemic stroke as well as its three main subtypes—based on large-scale genome-wide association studies (GWASs). Our two-sample MR analyses did not provide evidence for dental caries and periodontitis as the causes of cardiovascular diseases; sensitivity analyses, including MR–Egger analysis and weighted median analysis, also supported this result. Gene functional annotation and pathway enrichment analyses indicated the common pathophysiology between cardiovascular diseases and periodontal diseases. The associations from observational studies may be explained by shared risk factors and comorbidities instead of direct consequences. This also suggests that addressing the common risk factors—such as reducing obesity and improving glucose tolerance—could benefit both conditions.
Highlights
Cardiovascular disease (CVD) is a common and complex disease, especially in middleaged people those over 50 years old; its morbidity, disability, and mortality rates are relatively high, posing a serious threat to human health [1]
Forty-seven independent single-nucleotide polymorphism (SNP) associated with dental caries and periodontitis identified by the latest genome-wide association studies (GWASs) (p < 5 × 10–8) were selected for analysis [11] (Table 1)
We excluded SNPs that were absent and/or significant in GWASs of CVDs; among them, 44 SNPs were incorporated into the analyses of coronary artery disease (CAD) and heart failure (HF), 36 SNPs in the analyses of atrial fibrillation (AF), and 41 SNPs in the analyses of stroke (42 SNPs in ischemic stroke, 43 SNPs in cardioembolic stroke and large-artery atherosclerotic stroke, and 37 SNPs in small-vessel stroke)
Summary
Cardiovascular disease (CVD) is a common and complex disease, especially in middleaged people those over 50 years old; its morbidity, disability, and mortality rates are relatively high, posing a serious threat to human health [1]. The number of people dying from CVD is as high as 17 million, ranking first among all causes of death. Stroke, heart failure (HF), cardiomyopathy, and atrial fibrillation (AF) account for more than 95% of cardiovascular-disease-related deaths [1]. CVD is caused by heredity, environment, and their interactions; conventional risk factors for CVD are mainly lifestyle risk factors, including smoking, lipid metabolism disorders, hypertension, and altered glucose metabolism, all of which can be improved by lifestyle improvements. As knowledge of cardiovascular disease continues to increase, several chronic infectious, inflammatory, and immune diseases—such as periodontitis—are being found to be related to a significantly increased risk of adverse cardiovascular events
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