Infection as a Risk Factor for Heart Disease 

A number of pieces of evidence suggest a link between chronic infection and risk of atherosclerotic cardiovascular disease. Herpesviruses promote atherosclerosis in experimental animals, and they have been found in atherosclerotic plaques in humans. Chlamydia pneumoniae have been found in atheromatous plaques, and increased antibodies to these agents are associated with increased risk of new infarction in patients who have had myocardial infarction. Periodontal disease is also associated with an increased risk of coronary artery disease and peripheral vascular disease, even after adjusting for known confounding factors. Mouth organisms, such as Porphyromonas gingivalis and Streptococcus sanguis have been found in plaques. Injection of Cytomegalovirus, Chlamydia, or P. gingivalis into animal models does not cause atherosclerosis, but it does accelerate its progression. It is also noteworthy that C-reactive protein, which is produced by the liver in response to inflammation, is a non-specific marker of chronic inflammation, and it is considered to be an independent risk factor for atherosclerotic disease.

For an excellent review see Mattila KJ, et al.: Role of Infection as a Risk Factor for Atherosclerosis, Myocardial Infarction, and Stroke. Clin. Infect. Dis. 1998;26(3):719-734.

These observations led to a number of clinical trials that tested the possibility of treating high risk patients with antibiotics. Nevertheless, the results to date have been almost universally negative. (See editorial by Jeffrey L Anderson in N. Engl. J. Med.) Given the lack of effect of antibiotics, some believe that it may be the total "pathogen burden," i.e., the cumulative exposure to multiple atherogenic infectious agents that might enhance risk over a long period of time. While the role of infection remains to be established, the report below by Tonetti et al. suggests that chronic infection may predispose to atherogenesis by causing endothelial dysfunction.

Tonetti MS, et al.: Periodontal Disease Treatment of Periodontitis and Endothelial Function. N Engl J Med 2007;356:911-20.

From the abstract:

"We randomly assigned 120 patients with severe periodontitis to community-based periodontal care (59 patients) or intensive periodontal treatment (61). Endothelial function, as assessed by measurement of the diameter of the brachial artery during flow (flow-mediated dilatation), and inflammatory biomarkers and markers of coagulation and endothelial activation were evaluated before treatment and 1, 7, 30, 60, and 180 days after treatment.


Twenty-four hours after treatment, flow-mediated dilatation was significantly lower in the intensive-treatment group than in the control-treatment group (absolute difference, 1.4%; 95% confidence interval [CI], 0.5 to 2.3; P = 0.002), and levels of C-reactive protein, interleukin-6, and the endothelial-activation markers soluble E-selectin and von Willebrand factor were significantly higher (P<0.05 for all comparisons). However, flow-mediated dilatation was greater and the plasma levels of soluble E-selectin were lower in the intensive-treatment group than in the control treatment group 60 days after therapy (absolute difference in flow-mediated dilatation, 0.9%; 95% CI, 0.1 to 1.7; P = 0.02) and 180 days after therapy (difference, 2.0%; 95% CI, 1.2 to 2.8; P<0.001). The degree of improvement was associated with improvement in measures of periodontal disease (r = 0.29 by Spearman rank correlation, P = 0.003). There were no serious adverse effects in either of the two groups, and no cardiovascular events occurred.


Intensive periodontal treatment resulted in acute, short-term systemic inflammation and endothelial dysfunction. However, 6 months after therapy, the benefits in oral health were associated with improvement in endothelial function."