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Association between oral infections and cardiovascular diseases

Association between oral infections and cardiovascular diseases
Aino Salminen, Elisa Kopra, Laura Lahdentausta, John Liljestrand and Susanna Paju,
Abstract
The association between chronic oral infections and cardiovascular diseases (CVD) has been established in several extensive epidemiological studies. Most evidence is available on the association between periodontitis and atherosclerosis, and periodontitis has been recognised as an independent risk factor for CVD. The association between periodontitis and heart disease risk is independent of confounding factors such as patient's smoking, age, sex, socioeconomic status or obesity. From the infected periodontal pockets of periodontitis patients, periodontal bacteria and their virulence factors may access the systemic circulation. In the arterial wall, periodontal pathogens have several proatherosclerotic effects. Periodontitis also causes low systemic inflammation which contributes to the development of atherosclerosis. In addition, periodontitis has an unfavourable effect on blood lipid levels lipid metabolism. There are also some genetic factors that may predispose to both periodontitis and CVD. Intervention studies have shown that with appropriate periodontal treatment, it is possible to impact CVD risk factors. Periodontal treatment has been shown to improve systemic levels of inflammatory (e.g. C-reactive protein and interleukins), thrombotic (fibrinogen) and metabolic (triglycerides, total cholesterol, HDL cholesterol, HbA1c, i.e. long-term blood glucose) markers and to improve blood vessel endothelial function. Periodontal treatment is thus beneficial for general health in addition to oral health.
Introduction
Chronic oral infections comprise caries, periodontitis, apical periodontitis, pericoronitis and mucous membrane infections. Most research evidence is available on the association between periodontitis and CVD. The role of apical periodontitis as a potential risk factor for heart disease has also been investigated in recent years. A separate article will be published on this subject.
In both periodontitis and atherosclerotic heart diseases, chronic inflammation and degradation of the extracellular matrix play a key role in disease development and progress. In atherosclerosis, lipids accumulate in the vessel wall, forming an atherosclerotic plaque. The chronic inflammation in the plaque contributes to plaque growth and rupture. Local inflammation may also damage the vessel endothelium, causing the formation of blood clots. As it grows in size, the atherosclerotic plaque strives to remodel itself aggressively in order to avoid significant narrowing of the vessel diameter and to ensure blood flow. However, the remodelling weakens the plaque and makes it prone to rupture. A local blood clot forms at the rupture site, which may cause the entire artery to be blocked. Atherosclerotic plaque rupture leads to a CVD event, such as myocardial infarction.
The association between oral infections and CVD has been established in several extensive longitudinal and cross-sectional studies. In the late 1980s, the first studies on this subject were published by Finnish groups (1,2). The study by Mattila et al. observed that oral health was clearly worse in patients with myocardial infarction than in control population even when subjects' age, social class, smoking, blood lipids and diabetes were taken into consideration in the analyses (1). The study by Syrjänen et al. showed that periodontitis, periapical lesions and pericoronitis were more common in young and middle-aged stroke patients than in healthy controls (2).
Periodontitis has been recognised as an independent risk factor for CVD (3). However, in medicine, causality can only be established if strictly defined criteria are met (4). The notion of causality between periodontitis and cardiac diseases is supported by consistent research findings, convincing theoretical explanations and ample experimental evidence. However, establishing true causality between the two would require stronger scientific evidence, such as proof of the temporal sequence of events, i.e. the presence of periodontitis prior to heart disease.
The comprehensive oral infection burden has been illustrated with the help of various indices, some of which also take into account conditions such as caries, pericoronitis and retained dental roots in addition to marginal and apical periodontitis. Cross-sectional studies have shown these infection burden indices to be associated with coronary artery disease (5,6). In a 27-year follow-up study, the oral infection burden in childhood (caries and gingivitis) associated with the thickness of the carotid artery wall and the number of CVD risk factors in adulthood (7). There is also some indication of an association between diseases of the oral mucosa and CVD (8). For example, oral yeast infections may have potential systemic effects, as the treatment of prosthetic stomatitis has been shown to improve arterial function (9). As a whole, all oral infections may thus increase the risk of CVD through similar mechanisms as periodontitis.

Risk factors of chronic oral infections and CVD
Chronic oral infections and CVD share many common risk factors that modify predisposition to disease. Commonly recognised individual risk factors include age, male sex, smoking, heavy alcohol consumption, low socioeconomic status, diabetes, obesity, metabolic syndrome, nutrition-related factors and stress (10,11). In addition, similarities have been identified in the genetic profiles of periodontitis and CVD, and it is likely that in the future, common risk factors that are as yet unknown will be revealed. Tobacco is a significant risk factor for both periodontitis and CVD. It has multiple effects, including those on the circulation, microbiome, neutrophil function and cytokine production as well as on tissue rege
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