Background— Chronic infections, including periodontal infections, may predispose to cardiovascular disease. We investigated the relationship between periodontal microbiota and subclinical atherosclerosis. Methods and Results— Of 1056 persons (age 69±9 years) with no history of stroke or myocardial infarction enrolled in the Oral Infections and Vascular Disease Epidemiology Study (INVEST), we analyzed 657 dentate subjects. Among these subjects, 4561 subgingival plaque samples were collected (average of 7 samples/subject) and quantitatively assessed for 11 known periodontal bacteria by DNA-DNA checkerboard hybridization. Extensive in-person cardiovascular risk factor measurements, a carotid scan with high-resolution B-mode ultrasound, white blood cell count, and C-reactive protein values were obtained. In 3 separate analyses, mean carotid artery intima-media thickness (IMT) was regressed on tertiles of (1) burden of all bacteria assessed, (2) burden of bacteria causative of periodontal disease (etiologic bacterial burden), and (3) the relative predominance of causative/over other bacteria in the subgingival plaque. All analyses were adjusted for age, race/ethnicity, gender, education, body mass index, smoking, diabetes, systolic blood pressure, and LDL and HDL cholesterol. Overall periodontal bacterial burden was related to carotid IMT. This relationship was specific to causative bacterial burden and the dominance of etiologic bacteria in the observed microbiological niche. Adjusted mean IMT values across tertiles of etiologic bacterial dominance were 0.84, 0.85, and 0.88 ( P =0.002). Similarly, white blood cell values increased across tertiles of etiologic bacterial burden from 5.57 to 6.09 and 6.03 cells ×10 ⁹ /L ( P =0.01). C-reactive protein values were unrelated to periodontal microbial status ( P =0.82). Conclusions— Our data provide evidence of a direct relationship between periodontal microbiology and subclinical atherosclerosis. This relationship exists independent of C-reactive protein.

Evidence from epidemiologic studies suggests that periodontal infections are independently associated with subclinical and clinical atherosclerotic vascular disease. Although the strength of the reported associations is modest, the consistency of the data across diverse populations and a variety of exposure and outcome variables suggests that the findings are not spurious or attributable only to the effects of confounders. Analysis of limited data from interventional studies suggests that periodontal treatment generally results in favorable effects on subclinical markers of atherosclerosis, although such analysis also indicates considerable heterogeneity in responses. Experimental mechanistic in vitro and in vivo studies have established the plausibility of a link between periodontal infections and atherogenesis, and have identified biological pathways by which these effects may be mediated. However, the utilized models are mostly mono-infections of host cells by a limited number of ‘model’ periodontal pathogens, and therefore may not adequately portray human periodontitis as a polymicrobial, biofilm-mediated disease. Future research must identify in vivo pathways in humans that may (i) lead to periodontitis-induced atherogenesis, or (ii) result in treatment-induced reduction of atherosclerosis risk. Data from these studies will be essential for determining whether periodontal interventions have a role in the primary or secondary prevention of atherosclerosis.

Background and Purpose— Chronic infections, including periodontal infections, may predispose to cardiovascular disease. The present study investigates the relationship of periodontal disease and tooth loss with subclinical atherosclerosis. Methods— We enrolled 711 subjects with a mean age of 66±9 years and no history of stroke or myocardial infarction in the Oral Infections and Vascular Disease Epidemiology Study. Subjects received a comprehensive periodontal examination, extensive in-person cardiovascular disease risk factor measurements, and a carotid scan using high-resolution B-mode ultrasound. Regression models were adjusted for conventional risk factors (age, sex, smoking, diabetes, systolic blood pressure, low- and high-density lipoprotein cholesterol, race-ethnicity, education, physical activity) and markers of cultural background, healthy lifestyle, and psychosocial health. Results— Measures of both current and cumulative periodontitis became more severe as tooth loss increased. A significant association was observed between tooth loss levels and carotid artery plaque prevalence. Among those with 0 to 9 missing teeth, 46% had carotid artery plaque, whereas among those with ≥10 missing teeth, carotid artery plaque prevalence was ≈60% ( P <0.05). Conclusions— Our data suggest that tooth loss is a marker of past periodontal disease in this population and is related to subclinical atherosclerosis, thereby providing a potential pathway for a relationship with clinical events.

OBJECTIVE—Type 2 diabetes and periodontal disease are known to be associated, but the temporality of this relationship has not been firmly established. We investigated whether baseline periodontal disease independently predicts incident diabetes over two decades of follow-up. RESEARCH DESIGN AND METHODS—A total of 9,296 nondiabetic male and female National Health and Nutrition Examination Survey (NHANES I) participants aged 25–74 years who completed a baseline dental examination (1971–1976) and had at least one follow-up evaluation (1982–1992) were studied. We defined six categories of baseline periodontal disease using the periodontal index. Of 7,168 dentate participants, 47% had periodontal index = 0 (periodontally healthy); the remaining were classified into periodontal index quintiles. Incident diabetes was defined by 1) death certificate (ICD-9 code 250), 2) self-report of diabetes requiring pharmacological treatment, or 3) health care facility stay with diabetes discharge code. Multivariable logistic regression models assessed incident diabetes odds across increasing levels of periodontal index in comparison with periodontally healthy participants. RESULTS—The adjusted odds ratios (ORs) for incident diabetes in periodontal index categories 1 and 2 were not elevated, whereas the ORs in periodontal index categories 3 through 5 were 2.26 (95% CI 1.56–3.27), 1.71 (1.0–2.69), and 1.50 (0.99–2.27), respectively. The OR in edentulous participants was 1.30 (1.00–1.70). Dentate participants with advanced tooth loss had an OR of 1.70 (P < 0.05) relative to those with minimal tooth loss. CONCLUSIONS—Baseline periodontal disease is an independent predictor of incident diabetes in the nationally representative sample of NHANES I.