Editorial
Number of Missing Teeth as a Surrogate Marker for Risk of Atherosclerotic Disease
2023 Volume 30 Issue 10 Pages 1309-1310
Details
2023 Volume 30 Issue 10 Pages 1309-1310
See article vol. 30: 1350-1363
In the last three decades, periodontal disease (PD), which is the chronic inflammation of tooth-supporting tissues, has been observed to be a risk factor for the onset and progression of atherosclerotic disease (AD)1). Although the impact of PD is minor compared with other classical risk factors for AD, it cannot be ignored from the viewpoint of preventive medicine owing to its high prevalence and long disease duration2). Moreover, despite continued health promotion, the prevalence of AD and PD has not improved visibly. From my perspective as a dentist, the pathological relationship between the two diseases is expected to become more pronounced in a super-aging society in which the number of older people with PD is increasing.
Studies on AD, systemic diseases as risk factors, and their association with PD have been conducted from the perspectives of exploring pathological mechanisms and conducting clinical epidemiological studies. Regarding pathological mechanisms, early research proposed the effects of inflammatory cytokines produced by PD on arteries3) and the direct damage to arteries caused by PD pathogens such as Porphyromonas gingivalis4). Recently, new pathways have been explored using model animals. For example, swallowed P. gingivalis disrupted intestinal flora and altered intestinal mucosa permeability5). As a result, it has been hypothesized that PD contributes to the development of AD-related systemic disease through the exacerbation of liver and adipose tissue inflammation.
Clinical epidemiological studies have investigated the relationship between PD and AD using biomarkers obtained from various tests. Clinical examinations for PD include detailed examinations that evaluate pathological changes in the periodontal tissue, such as periodontal pocket depth and attachment loss, on a tooth-by-tooth basis; examinations that evaluate a mouth-by-mouth basis, such as the community periodontal index; and saliva tests for detecting occult blood due to inflammation and PD-causing bacteria. Naturally, in the case of large-scale epidemiological studies, there is a tendency to select simpler methods in consideration of human resources and the burden on participants. The number of missing teeth (or the number of existing teeth) in middle-aged and older people has been recognized as a surrogate marker for the burden of periodontal tissue inflammation from the past to the present, which can be measured most easily6) because the most common cause of tooth loss is periodontal tissue destruction attributable to the development of PD.
In recent years, with increasing interest in the relationship between oral health and systemic health in Japan, the results of various large-scale cohort studies targeting the general population have been reported. One example is Nagahama study on 10,000 residents of Nagahama City, Shiga prefecture, which is being conducted since 2007. Fukuhara et al. have reported remarkably interesting findings about the association between PD and AD by combining multiple PD markers7). The three markers they used were pocket depth, which represents the initial reversible inflammatory burden of PD, attachment loss, and the number of missing teeth, which represents the cumulative inflammatory burden from the past to the present. The maximum intima-media thickness (max-IMT) of the common carotid artery was used as an index of AD. No association was found between pocket depth and max-IMT. However, multivariate analysis after adjusting for conventional risk factors showed that a large number of missing teeth (＜9 remaining teeth) was significantly associated with max-IMT. In addition, the presence of two or more areas with an attachment loss of ≥ 4 mm showed an association with max-IMT, and no association was observed between attachment loss and max-IMT in the group without tooth loss. Based on these findings, the authors concluded, “The association between PD and AD was suggested to depend on the intensity, extent, and duration of inflammation in PD.” This finding faithfully supports the recognized characterization of PD as a systemic low-grade inflammatory response associated with oral tissues.
In the Suita study, which began in 1998 as a large-scale cardiovascular disease cohort, in Suita City, Osaka Prefecture, dental checkups were introduced in 2008, and I have been involved in dental research. Kida et al. used CPI (0–4) as a marker of PD severity in 1472 participants aged 50–70 years to determine whether hypertension affects the relationship between PD and IMT in the common carotid artery8). They found that the mean IMT increased in proportion to the severity of PD in the normotensive group, but the increase was not strictly significant in the hypertensive group. Further, they found no association between PD severity and max-IMT. These findings suggest that the inflammatory burden caused by PD and that caused by hypertension interact with each other in the relationship between PD and AD and that the appearance of the association differs depending on the markers of PD and AD.
On the other hands, tooth loss due to severe PD leads to the deterioration of masticatory ability. People with decreased masticatory ability tend to avoid chewy foods and consume soft processed foods, which inevitably increase their intake of carbohydrates, lipids, and sugars9). It is likely to cause the incidence and progression of lifestyle-related diseases such as obesity, hyperlipidemia, and impaired glucose tolerance, which are components of the metabolic syndrome. In the Suita study, masticatory performance was objectively evaluated using a standardized test food (gummy jelly), and longitudinal analysis revealed that men with reduced masticatory performance were found to have a higher risk for the novel development of metabolic syndrome even after adjusting for the effects of PD10). Therefore, it is necessary to consider the number of missing teeth as a surrogate marker for measuring the risk of AD not only from the duration and severity of exposure to inflammation by PD but also from the pathway of poor nutritional intake due to decreased masticatory performance.
Elucidating the causal relationship between oral health and AD is challenging because of the influence of various systemic diseases, such as components of the metabolic syndrome that are risk factors for AD, and the mutual effects of these diseases and oral health, which exist as confounding factors. However, the development of animal models in experimental pathology and the utilization of diverse oral health parameters in clinical epidemiology are expected to drive future research on this topic.
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