Infection and Cardiovascular Disease: The Atherosclerosis Risk in Communities Study

Abstract

Infection has been identified as both a chronic and acute risk factor of cardiovascular disease (CVD). Despite the growing body of evidence, additional research elucidating the relationship between infection and CVD is needed. This dissertation employs longitudinal data from the Atherosclerosis Risk in Communities (ARIC) study, the Longitudinal Investigation of Thromboembolism Etiology (LITE) ancillary study, the Dental-ARIC (D-ARIC) ancillary study, and the corresponding ARIC study participant Centers for Medicare and Medicaid Services (CMS) data to examine the relationship between infection and CVD. In the first manuscript we assessed the longitudinal relationship between self-reported periodontal disease and clinical periodontal disease and incident venous thromboembolism (VTE). Self-reported periodontal disease was associated with 30% higher VTE risk that remained significant or borderline significant after adjustment. Crude associations between clinical periodontal disease classifications were attenuated with adjustment and were no longer significant. In the second manuscript we assessed the longitudinal relationship between history of endodontic therapy (ET) and incident coronary heart disease (CHD), ischemic stroke, heart failure, and VTE. We found no significant associations between self-reported history of ET and any of our outcomes of interest that remained after adjustment. In the final manuscript we used a case-crossover study design to evaluate infection as a potential trigger of CHD, ischemic stroke, and VTE. Infection was associated with higher odds of CHD, stroke, and VTE up to 90 days following the infection. The association between infection and CVD/VTE was graded such that the infection-CVD/VTE association was highest immediately following the infection and decreased as the time since the infection increased. Generally, outpatient infection was a weaker CVD/VTE trigger compared to all infections. Further research is needed to pinpoint if periodontal disease is independently associated with VTE risk and if periodontal prevention and treatment could reduce VTE risk. Our results do not support an independent association between endodontic therapy and CVD or VTE. The results of the third manuscript provide evidence in support of our hypothesis that infection is a CVD/VTE trigger. Patients with an infection who are at elevated risk of CVD should be considered potential candidates for CVD prophylaxis during and immediately after infection to reduce the otherwise elevated CVD/VTE risk.