Periodontal disease – important to consider in cardiovascular disease prevention

KEYWORDS:

• Myocardial infarction
• periodontitis
• risk factor
• inflammation

The possibility of a connection between oral infection and systemic health was suggested already during the nineteenth century [1] and a discussion on the oral focal infection theory continued, a debate that is still going on. In the late 1980s, after suggestions by Mattila and Beck and co-workers, an increased interest on the association between oral health and cardiovascular disease emerged [2,3]. Since then, the interest for this link has persevered.

Periodontitis is a chronic inflammatory condition following bacterial colonization of the gingiva that successively degrades the tissues attaching the teeth to the alveolar bone. Its mildest form, gingivitis or a bleeding gum, does not affect the underlying supporting structures of the teeth and is reversible with treatment. Periodontitis is common and it has been estimated that 46% of US adults have periodontitis [4] and its severe form, which often result in tooth loss, affect 5–15% worldwide [5]. Furthermore, in the presence of an oral infection or inflammation, the inner wall of the gingival pocket will become ulcerated and its role as a barrier to the systemic circulation is disrupted. Under these conditions, bacteria as well as bacterial products and inflammatory mediators can move from the gingival pocket to the well vascularized periodontal tissues and into the circulation.

Atherosclerosis is a multifactorial disease promoted by chronic inflammatory conditions. An activation of systemic inflammation increases the risk for rupture of the atherosclerotic plaques and is considered of importance for the onset of acute coronary syndromes [6,7]. Cardiovascular disease, an expression of atherosclerosis, is the major cause of mortality in the western world contributing to almost half of all deaths in Europe [8]. Although a multitude of risk factors including smoking, hypertension, dyslipidemia, and diabetes are known to be behind a large proportion of myocardial infarctions (MIs) [9], there are still gaps in the knowledge regarding causes that contribute to the progress of atherosclerosis and cardiovascular events. It has been postulated that an association between periodontal and cardiovascular diseases may be one of these gaps [10]. Both conditions are promoted by similar risk factors, which may be a likely, but perhaps not the only, reason for the connection. An alternate explanation is that systemic inflammation promoted by periodontitis accelerates the atherosclerotic vascular injury and plaque rupture. Then, periodontitis becomes a cause of, rather than just a condition that co-exists with cardiovascular disease [7,11]. That DNA from oral bacteria has been identified in arterial plaques further support that there is a link between the oral microflora and cardiovascular disease [12]. Together with studies in which periodontal intervention favorably influenced inflammatory markers of cardiovascular risk for up to six months after the intervention [13,14], these findings were taken as evidence of a causal relationship. These studies must, however, be interpreted with caution due to the limited study populations, an aggravation of systemic inflammation during the first days after the periodontal intervention, the use of surrogate endpoints as a substitute for cardiovascular morbidity and mortality and incomplete information on shared risk factors of potential importance. This was further supported by an American Heart Association (AHA) statement saying…‘statements that imply a causative association between periodontal disease and specific atherosclerotic vascular disease events or claim that therapeutic interventions may be useful on the basis of that assumption are unwarranted’ [15].

A large, Swedish, multicenter, case-control study, PAROK RANK, recently investigated periodontitis and its relation to coronary artery disease [16]. The study recruited 805 patients <75 years old with a first MI and 805 controls matched for age, gender, and geographical area. The main finding was that the presence of moderate to severe periodontitis was independently associated with a first MI, increasing the risk by 28%. This association was particularly apparent in participants below the age of 65 years and among women (data on file). Thus, PAROKRANK supports the possibility of an independent relationship between periodontitis and cardiovascular disease [17]. The study has several strengths, among them a study population recruited from a nationwide geographical area and covering a variety of educational and socioeconomic conditions. The upper age limit of 75 years and that a first MI, representing both atherosclerosis and plaque vulnerability, was used as the expression of cardiovascular disease made the investigation less influenced by a multiplicity of concomitant disorders. Moreover, the presence and severity of periodontitis was based on alveolar bone loss studied by means of a radiographic method and interpreted at one core center. Still, it is an observational investigation and as such, it cannot be used as proof of a causal relationship.

A pre-planned long-term follow-up of PAROKRANK focusing on the incidence of recurrent cardiovascular mortality and non-fatal events in relation to periodontitis will start during the fall of 2016. Both cases and controls will be studied with the hypothesis that the event rate will be higher among study participants with moderate to severe periodontitis than in those without oral disease. If the hypothesis is confirmed, it will add to the understanding of the true nature of the association between periodontitis and cardiovascular disease, moving it toward a causal relationship.

What are the practical consequences of the knowledge derived from PAROKRANK? It is, if not the largest, one of the largest studies of its kind, and it circumvented several shortcomings of previous investigations thereby providing strong support to the assumption that periodontal and cardiovascular diseases are closely linked. A reasonable conclusion may be that it underlines the importance to look for, and when present, treat periodontal disease not only to improve dental but presumably also cardiovascular health. Prevention of periodontitis is of course the preferred option. However, this would put extra demand on regular dental health checks since it usually is a slowly progressing disease that might be totally painless and therefore may remain undetected by those afflicted for a long time. Good oral health can prevent most cases of periodontitis, but how do we get there? Community programs for the preservation of cardiovascular health underlines the importance of exercise, a balanced diet, and smoking cessation, advice that is of importance for oral health as well. In this perspective, education programs promoting the importance of oral health with a goal of preventing systemic diseases may add to the willingness of patients to cope with such instructions. Such programs are best started already in younger ages, as part of school programs, where children and young adults are encouraged to brush and floss teeth daily and to lower sugar and acidic beverage intake.

That the oral cavity is an important part of the body is obvious to us in the medical profession and hopefully among large parts of the general population. But, when it comes to the health care provision, it seems that there is a tendency to keep the mouth and its problems apart from the rest of the body. Increased collaboration, not the least in the form of educational programs recruiting their audiences both from the dental and medical professions, may be one way to reduce this separation. To take a look in the mouth and to know what to look for may become an important part of ordinary medical checkups. Likewise, it may be beneficial to ask for risk factors or signs of cardiovascular disease in conjunction with dental exams.

In conclusion, and taking present knowledge into account, it is too early to recommend treatment of periodontitis to prevent future MI. Still, we suggest a closer collaboration between the dental and medical health professionals. Dentists should ask patients with moderate to severe periodontitis about other risk factors and signs of cardiovascular disease. Cardiologists should, besides their stethoscope, be equipped with spatulas and look for periodontal disease and when needed refer the patient to a dentist. Meanwhile, we need further research in this important field of medicine on the border between the two separate medical branches. PAROKRANK will hopefully, through continued investigations as discussed above and via detailed analyses of inflammatory markers and other matters of interest, bring additional information on the intriguing relation between the oral cavity and the circulatory system.

Declaration of interest

The PAROKRANK study was supported by grants from AFA Insurance, Swedish Heart-Lung Foundation, Swedish Research Council, Swedish Society of Medicine and Stockholm County Council (ALF project and Steering committee KI/SLL for odontological research). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.