Periodontitis, a prevalent disease, is characterized by chronic inflammation of gum tissue, including the ligaments and bony structures that hold the teeth in place. Poor oral health has been associated with cardiovascular and cerebrovascular diseases: patients who have coronary artery disease (CAD) have a higher prevalence of periodontal disease (PD),¹ and patients who have PD might be at increased risk of CAD, myocardial infarction, and stroke.^2,3 Because CAD is a major cause of chronic heart failure (CHF), an association between periodontitis and CHF seems probable.

Periodontitis and CHF share risk factors such as smoking, diabetes mellitus, alcohol consumption, hypertension, and low socioeconomic status.⁴ Periodontitis might produce a biological burden of endotoxin and inflammatory cytokines that initiates and exacerbates inflammation, atherogenesis, and thromboembolic events.⁵ Inflammatory activation has been recognized in CHF patients regardless of its underlying cause,⁶ indicating a probable association between periodontitis and CHF.

So far, the relationship between CHF and periodontitis has not been studied. We therefore sought to evaluate the prevalence of periodontitis in CHF patients with respect to the underlying cause and severity of heart failure symptoms. In addition, we compared the prevalence of periodontitis in CHF patients to that in the age-adjusted general population.

Patients and Methods

We recruited patients who had visited the outpatient heart-failure clinic at the University of Heidelberg, Germany, from December 2010 through March 2011. The diagnosis of CHF was established in accordance with current guidelines on the basis of typical symptoms and signs resulting from an abnormality of cardiac structure or function.⁷ Patients had to have at least 2 of their own teeth per dental sextant to enable a comprehensive dental evaluation. Anyone who had recently undergone periodontal treatment was excluded from this study, because dental examination might have interfered with wound-healing. Patients who needed endocarditis prophylaxis were also excluded, because probing of the periodontal pocket might have led to bacteremia. The extent of periodontitis might be influenced by other noncardiac diseases, such as neutropenia, leukocyte adhesion deficiency, glycogen storage disease, and hypophosphatasia; therefore, to prevent data bias, we excluded CHF patients who had concomitant major diseases.

This prospective study conformed to the principles outlined in the Declaration of Helsinki and was approved by the local ethics committee. All participating patients provided written informed consent.

Of 208 consecutive patients who had visited the outpatient heart-failure clinic at the University of Heidelberg for evaluation of heart failure and who were screened for study inclusion, 71 patients qualified. We excluded 137 patients because of edentulism (n=82), the need for endocarditis prophylaxis (n=16), New York Heart Association (NYHA) class IV functional status (n=13), and other reasons (n=26). Table I shows the baseline characteristics of the study population.

TABLE I. Baseline Characteristics of the 71 Study Participants

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The diagnostic investigations for heart failure included taking patients' medical histories and performing physical examinations, laboratory tests, electrocardiography, echocardiography, and exercise tests. Left ventricular ejection fraction (LVEF) was established by means of the Simpson method. The cause of heart failure was confirmed after left-sided heart catheterization in all patients. Medication prescription was at the discretion of the referring physician. To exclude interobserver variability, all patients underwent dental examination by the same experienced dentist. Dental evaluation involved taking patients' histories, performing oral inspections, and probing periodontal pockets with a World Health Organization (WHO) probe. The spherical top of the probe prevents endothelial penetration and facilitates palpation of subgingival concrements. The probe was inserted to the ground of the gingival sulcus in 6 points at each tooth (mesiobuccal, buccal, distobuccal, mesio-oral, oral, and disto-oral). The distance from the marginal gingiva to the sulcus ground defined the depth of the periodontal pocket. Gum-bleeding upon probing, the presence of calculus, and periodontal pocket depth were determined, and the periodontal screening index (PSI) was calculated for each tooth.⁸ The highest score in a sextant was recorded as the PSI score for that sextant. Scores of 1 and 2 were defined as gingivitis; scores of 3 and ≥4 signified moderate and severe periodontitis, respectively.

Results

Twenty-eight patients (39%) had heart failure caused by ICM, and dilated cardiomyopathy (DCM) was present in 43 patients (61%). Gingivitis (PSI 1/2) and moderate periodontitis (PSI 3) were found in 17 patients each (24%), and 37 CHF patients (52%) had severe periodontitis (PSI 4). No patient had completely healthy gum tissue. Periodontitis was more prevalent than gingivitis in all CHF patients regardless of the underlying cause of heart failure (P=0.03).

In patients who had severe periodontitis, 6-minute walking distance was significantly shorter than in those who had moderate periodontitis or gingivitis (P <0.01). In addition, the patients who had severe periodontitis were older than those who had gingivitis (P=0.02). Table II shows the patients' characteristics according to severity of PD.

TABLE II. Patient Characteristics in Accordance with Severity of Periodontal Disease

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In our comparison of patients who had severe periodontitis with patients who had gingivitis, univariate logistic regression models that included all baseline characteristics revealed that age, the diagnosis of DCM, 6-minute walking distance, hyperlipidemia, statin use, and therapy with aldosterone antagonists were predictors of severe periodontitis (Table III). However, in the multivariate model, only the 6-minute walking distance was an independent predictor of severe periodontitis (odds ratio [OR]=1.008; 95% confidence interval [CI], 1–1.02; P=0.05).

TABLE III. Univariate Logistic Regression Results for Predictors of Severe Periodontitis versus Gingivitis

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The characteristics of patients who had DCM differed substantially from those who had ICM (Table IV). In comparison with the ICM patients, the DCM patients were younger (P=0.01) and had a higher prevalence of gingivitis. In contrast, severe periodontitis was diagnosed predominantly in the ICM patients (P=0.03). Moreover, the ICM patients had more severe heart failure, as indicated by lower LVEF (P=0.03), higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (P=0.001), and shorter 6-minute walking distances (P=0.007).

TABLE IV. Patient Characteristics in Accordance with Cause of Heart Failure

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Table V shows the 6 significant predictors from univariate regression analyses of ICM versus DCM patients, including all baseline characteristics. In the multivariate model, only statin use was an independent predictor of ICM (OR=0.4; 95% CI, 0.005–0.33; P <0.01).

TABLE V. Univariate Logistic Regression Results for Predictors of ICM versus DCM

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Comparison with the General German Population

The mean age in our study cohort was 54 ± 13 years. The 4th German Dental Health Survey reported the prevalence of PD in adults (age range, 35–44 yr) and seniors (age range, 65–74 yr).⁹ To compare the prevalence of periodontitis among CHF patients with that in the general population, we conducted linear interpolation. Table VI shows the interpolated age-adjusted prevalence of gingivitis, moderate periodontitis, and severe periodontitis in the general German population.

TABLE VI. Linear Interpolation of Age-Related Prevalence of Periodontal Disease in the General German Population

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The prevalence of severe periodontitis was highest in CHF patients, whereas moderate periodontitis was prevalent mainly in the general population (P <0.00001) (Fig. 1).

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Discussion

We sought to determine the prevalence of PD in CHF patients with respect to the underlying cause and the extent of severity of CHF. To our knowledge, this is the first such study. Our main findings are:

• The prevalence and severity of PD are higher in CHF patients than in the age-adjusted general population. This is true in ICM and DCM.

• Periodontitis severity is not independently related to the cause of CHF.

• Periodontitis severity does not correlate with the extent of heart failure symptoms.

Periodontitis and Heart Failure. So far, only one study has focused on an association between periodontitis and heart failure: in 2004, Wood and Johnson¹⁰ retrospectively analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III), referring to the presence of periodontitis, a history of CHF, and monthly tomato consumption. They reported a dose–response relationship between dietary monthly tomato consumption and self-reported CHF risk in individuals who had periodontitis. Although the study comprised more than 17,000 patients, its informational value is limited because of the imprecise characterization of CHF. Moreover, the cause of heart failure was not reported.

Periodontitis and Cause of Heart Failure. In our study, the prevalence of periodontitis was high regardless of the cause of CHF. Although severe periodontitis was diagnosed predominantly in ICM patients, no significant association between the severity of periodontitis and the cause of CHF was noticed after adjustment for covariates. Our study is the first to describe the prevalence and severity of periodontitis in DCM patients; however, the association between CAD and periodontitis outside heart failure has been investigated in epidemiologic studies during the past 2 decades. Most of those investigators reported a low-to-moderate positive association between periodontitis and CAD.³ A meta-analysis of 22 case-control and cross-sectional studies yielded a pooled OR of 2.35 (95% CI, 1.87–2.96; P <0.0001) for the simultaneous presence of cardiovascular disease in patients who had periodontitis.¹¹

Experimental data tend to support the association between CAD and periodontitis. Oral pathogens have been identified in up to 44% of atherosclerotic plaques,¹² and a high antibody response against the major periodontal pathogens seems to be associated with prevalent CAD.¹³ Furthermore, dental-plaque bacteria such as Streptococcus sanguis induce platelet aggregation by expression of the platelet aggregation-associated protein in vitro.¹⁴ Intravenous infusion of these pathogens in rabbits can cause changes in electrocardiographic values, heart rate, blood pressure, and cardiac contractility.¹⁵

To date, no reported data have pertained to the prevalence of periodontitis in patients who have DCM. However, an association between periodontitis and DCM is highly likely for various reasons. Inflammatory activity is present in both diseases. Periodontitis is defined as a chronic inflammation of gum tissue; and, in patients who have DCM, inflammation is part of general neurohormonal activation. Myocardial infiltration by T-lymphocytes and macrophages might lead to cytokine release and cardiac tissue damage.¹⁶

The increased activity of matrix metalloproteinases (MMPs) has been implicated in both periodontitis and DCM. The MMPs are a family of zinc- and calcium-dependent endoproteinases that mediate the degradation of extracellular-matrix and basement-membrane components. Among these, increased activity of MMP-1, -2, -3, -8, and -9 has been found in inflamed human periodontal tissues and DCM-affected hearts.^17,18

Finally, there appears to be a familial predisposition for both periodontitis and DCM,^19,20 and genetic factors might account for up to 50% of periodontitis.²¹ Candidate genes for periodontitis include inflammation mediators and structural components of periodontal tissues.²² Variants in perhaps more than 20 genes might be associated with periodontitis.²² In contrast, the oral transmission of infectious agents appears to play only a minor role in periodontitis. The transfer of infectious agents does not necessarily result in colonization or infection of the host, and even individuals who harbor putative pathogens frequently do not manifest signs of periodontitis.²³

Severity of Periodontitis and Heart Failure Symptoms. Although we found that NYHA functional class was not different among groups, physical capacity, as evaluated by 6-minute walking distance, was significantly lower in patients who had severe periodontitis. In addition, the 6-minute walking distance was the only independent predictor of severe periodontitis. We found no other relevant data in the medical literature. In our study, patients who had severe periodontitis were older than those who had gingivitis, and CAD was frequently present. Thus, older age, concomitant peripheral vascular diseases, or both might have impaired the walking distances.

Statin Use and Severity of Periodontitis. Results of prior studies have suggested that statin use has a positive influence on periodontal lesions.^24–27 The authors assumed that the beneficial effects of statins were mediated by their pleiotropic anti-inflammatory effect on periodontal tissue.^26,27 Then again, in the present study, statin use was higher in patients who had severe periodontitis than in the other groups. However, this might indicate the higher proportion of patients who had ICM, rather than the severity of periodontitis. In the multivariate model, we noted no significant independent association between statin use and periodontitis severity.