A prospective study of cytomegalovirus, herpes simplex virus 1, and coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Conflicting evidence exists implicating infectious disease in the pathological processes leading to coronary heart disease (CHD). The objective of this article is to describe the relationship of previous infection with cytomegalovirus (CMV) and herpes simplex virus 1 to incident CHD in a population-based cohort study. Methods: Using a nested case-cohort design from the Atherosclerosis Risk in Communities Study, antibody levels to CMV and herpes simplex virus i were determined in serum samples that had been frozen at the baseline examination in participants free of CHD. Determinations were made in those who developed incident CHD (n=221) during follow-up of up to 5 years from baseline and in a stratified random sample of all participants (n=515). Results: The population with the highest antibody levels of CMV (approximately the upper 20%) showed an increased relative risk (RR) of CHD of 1.76 (95% confidence interval, 1.00-3.11), adjusting for age, sex, and race. After adjustment for additional covariates of hypertension, diabetes, years of education, cigarette smoking, low-density lipoprotein and high-density lipoprotein cholesterol levels, and fibrinogen level, the RR increased slightly. Based on a priori hypotheses, the RR of CHD at the highest antibody levels in individuals with diabetes was particularly large but with wide confidence intervals (RR, 9.2; 95% confidence interval, 1.8- 47.0), and the interaction between high levels of antibody to CMV and diabetes was statistically significant (P=.05). There was no association of CHD with the highest herpes simplex virus 1 antibody levels (adjusted RR, 0.77; 95% confidence interval, 0.36-1.62). Conclusions: High levels of CMV antibodies are significantly associated with incident CHD. Infection with CMV, particularly in more susceptible disease states such as diabetes, may be an important risk factor for CHD.