Oral Infections and Cardiovascular Disease

The clinical entity “coronary heart disease (CHD)” comprises two major components – atherosclerosis (AS) of the coronary arteries and acute thrombosis that occasionally occurs superimposed on an atherosclerotic artery wall, causing various types of acute coronary syndromes (ACS) like acute myocardial infarction (AMI). As CHD is a major cause of mortality and morbidity in the Western societies, massive research efforts have been invested in it. It has become clear e.g. that the triggering factors for acute manifestations of CHD are not identical to the slow-acting, classic risk factors for coronary AS. The large impact of hypercholesterolemia, hypertension and smoking on the development of CHD has been established already some decades ago. Yet they do no explain all clinical and epidemiological features of CHD. These major CVD risk factors have dominated the research filed, and it has not always been easy for other potential risk factors to receive attention and research funding.

Cardiovascular disease (CVD) is now considered to be a multi causal disease. Numerous studies have focused on major risk factors as hypertension, smoking, cholesterol, genes, biomarkers, sex, and family history. Yet they do not explain all CVD events and the associated patophysiology. Mounting evidence is being published on the association of oral infections, periodontal infections in particular, to the disease processes of the cardiovascular system leading to myocardial infarction, stroke, or other cardiovascular diseases. Different causal pathways are being explored. The question arises as to when we have sufficient evidence of causality to mark a factor amenable to prophylactic measures against cardiovascular disease. Causality is the term for studying the association between different factors and the development of a disease or health condition and the disease occurrence and its trends. Causal inference involves making conclusions from current knowledge. Which theoretical framework is available when studying disease and risk factors? Causality is discussed in the context of epidemiology, statistics, philosophy, and evidence based medicine.

Periodontal diseases are a group of pathological conditions of the supporting tissues of the teeth. They are generally accepted as polymicrobial infections elicited by a complex of bacterial species that interact with the release of a broad array of inflammatory cytokines, chemokines and mediators from the host, some of which lead to destruction of the structures of the periodontium and alveolar bone [1]. The purpose of this chapter is to give the reader a brief overview of factors which are considered as risk factors for development of periodontal diseases.

Coronary heart disease (CHD) reached epidemic proportions during three to four decades, and returned to lower levels after about two decades during the 20th century. The factors which were associated with its increase and decline were blood lipids, blood pressure, smoking, body weight and diabetes. These factors are not exclusive entities. They are both overlapping and interrelated. Thus any analysis of their impact on disease frequency and effects of intervention may be difficult when it comes to making a distinction of each factor’s contribution. All these factors are associated with oxidation and inflammation; essential mechanisms behind atherosclerosis and thrombosis. Two of the factors stand out as the most important explanatory factors as to why the CHD epidemic reached such dramatic levels; the adverse dietary pattern affecting blood lipids, and cigarette smoking. Other factors contributed also but their contribution to changes in disease frequency was more modest. The declining CHD incidence and mortality was subsequent both to declining cholesterol levels and cigarette smoking. These changes coincided with declining intake of saturated fat, but recent meta-analyses do not support a causal role of saturated fat. Industrially produced trans fatty acids often consumed together with saturated fat are likely to have played a more important role as they are directly affecting both oxidation and inflammation. Some of the alleged risk factors are “innocent” bystanders, others have a direct detrimental effect, but they may come in the same package, served at the same meal, or be results of the same lifestyle habit. This will affect the results of the analyses and only underlines the need to assess epidemiological data in a biological context, before one draws firm conclusions on risk factors as direct and causal factors.

The present chapter focuses on oral bacteria detected in cardiovascular diseases. It starts describing the diversity of the bacterial flora in the mouth and in the blood stream, invasion of bacteria in coronary artery cells, bacteria of coronary artery walls, bacteria of atheromas/atherosclerotic lesions, bacteria of aneurysms, and bacteria in aortic valve stenosis and infective endocarditis. The review ends with concluding remarks on the possible significance of oral bacteria in cardiovascular diseases.

There is a growing awareness of the role of oral pathogens in cardiovascular disease. Chronic oral disease such as periodontitis, leads to inflammation and bleeding of the gums. This bleeding provides a viable portal of entry for the bacteria to the circulation. Once in the circulation oral bacteria can interact with circulating platelets. Their ability to support platelet adhesion and induce platelet aggregation are critical steps in the pathogenesis of the infective process. Oral bacteria use multiple mechanisms to interact with, and activate platelets thus contributing to cardiovascular disease. This chapter will review the various mechanisms oral bacteria use to interact with platelets.

Association between periodontitis and cardiovascular disease can be explored by a various set of methods. Correlation between microflora in periodontitis and atherosclerosis has to be solved at the strain level. The choice of methods depends on lab facilities, and skilled hands. Combining different methods avoid false positive observations and verify accurate identifications. Serology reveals the host response as systemic versus local by analyzing body fluids for inflammation biomarkers and antibodies against invading pathogens at species level. Scanning electron microscopy (SEM) is useful to explore the localization and visualize the morphology of the microorganisms in the tissue. With the fluorescence in situ hybridization (FISH) technique, specific gene sequences can be explored in intact cells of the tissue sample and microorganisms can be differentiated at strain level. Proteomic analysis of the tissue sample reveals the active part of the infection, and detection of peptides that can be linked to specific microorganisms at strain level and host factors such as immune related factors. High through-put sequencing of total DNA from tissue samples reveals sequences from the tissue as well of microorganisms (metagenomics) but can be difficult to solve 100% because of lack of reference genomes of yet unidentified microorganisms when blasting those small sequence fragments. A sequence profile can be performed by cloning the 16S/18S PCR product or a genus-specific hybridization profiles by microarray hybridization. Whereas fingerprinting techniques based on pure bacteria or Candida make a specific fingerprinting pattern that can indicate strong correlation or not between samples from the same patient.

Periodontal disease is an infectious disease affecting more than 50% of the adult population, and epidemiological studies reveal an increased risk for cardiovascular disease and stroke among individuals with periodontal disease. Hence, prevention and treatment of periodontal diseases through the control of periodontal infections are import issues not only for the oral health but also the general health of the individual. In this chapter current concepts regarding treatment approaches for establishing and maintaining periodontal infection control are discussed.

If oral infection causes CVD, there is a moral imperative to avoid CVD by reducing oral infections. But what if it is not clear whether oral infection causes CVD? Then we are faced with conceptual, methodological and moral challenges. The literature, as the rest of this book, is focusing on methodological challenges, trying to show that and how oral infections cause CVD. However, there has been little or no attention on the conceptual and moral challenges, which are the topics for this chapter. A closer analysis of the scientific basis for claiming that oral infection causes CVD reveals a series of moral issues. These stem from a) how to choose between the many conceptions of causality, and from b) the moral challenge of preventing harm when there is an unclear or weak causal relationship between oral infection and CVD or c) when various kinds of uncertainty prevail. The challenge of how to act under uncertain circumstances comes out as questions of resource allocation and prioritization, but it also poses issues of medicalization and not causing unnecessary health anxiety. Hence, although the literature is void of discussing moral challenges with the relationship between oral infection and CVD, the challenges are ample.

Normal oral bacteria have an important function in the mouth in being a barrier towards unwanted microbes, they exhibit immunological properties, and saliva has a buffering capacity against their acid production in caries activity. Repressed normal flora causes overgrowth of pathogens. Unless adequately controlled an overload of bacteria will arise with the result of infections. Oral bacteria and their infection products produce a reaction by the immune system in the defense of potential harm from infections. It is apparent that many factors are involved as oral bacteria and their bacterial products have no function in the circulatory system. Chronic periodontitis and dental infections are to a great extent lifestyle diseases and as such are preventable in most instances. Coronary heart disease is also considered to be greatly influenced by lifestyle factors and is also acknowledged to be a disease of inflammation and oxidation. The possible outcomes of cardiovascular disease considered are atherosclerosis, thrombosis, myocardial infarction, stroke, aneurysm of the aorta, and heart valve disease. This review examines the relations between the two diseases whether these are strong enough to establish oral infections as an independent risk factor for CVD. Bridging the knowledge gap between these disease entities is important and this research needs to be further developed.

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