INFECTION AND CARDIOVASCULAR DISEASE

Medstar Research Institute, Hyattsville MD

Investigators

Linked publications & trials

Abstract

Recent studies have associated evidence of Chlamydia pneumoniae infection with coronary and carotid atherosclerosis and evidence of increased infection with cytomegalovirus (CMV) in patients developing restenosis or with atherosclerosis. Several other common pathogens have been less consistently associated with atherosclerosis. Altered parameters of inflammation and hemostasis have been identified as prognostic factors of myocardial infarction and have been linked as possible pathogenetic mechanisms. Recent studies have indicated that peripheral blood mononuclear cells (PBMC) from patients with coronary artery disease frequently called Chlamydia pneumoniae DNA and stimulation of PBMCs can reflect an unsuccessful host cellular immune response to CMV associated with elevated C-reactive protein (CRP). This proposed study is both a nested case-cohort study and a nested cohort analysis within the Strong Heart Study (SHS), an ongoing cohort study of 4,549 American Indians. This study will utilize previously collected specimens, baseline data, and the planned ultrasound measurement of carotid wall thickness (IMT) in SHS participants. Within the initial SHS cohort, 400 definite cases of incident myocardial infarction, coronary heart disease, and stroke will be compare with 400 control individuals with no such diagnoses and matched for age, gender, and residence. Their prior serum specimens will be analyzes for Chlamydia pneumoniae-specific IgG, IgM antibody, for cytomegalovirus-specific IgG antibody, and for CRP. In addition, assays will be performed for antibodies to Helicobacter pylori, hepatitis A virus, (HAV) and herpes simplex virus (HSV) type 1 and 2. Correlations will be made with baseline parameters of lipids, coagulation, and adjusted for potential confounding variables of tobacco use, pneumonia, and altered pulmonary function. An additional analysis of a subcohort, the above 400 controls, will be performed looking at the outcome of their carotid IMT, a parameter of subclinical atherosclerosis, in relation to serologic results indicating a prior exposure to CMV, Chlamydia pneumoniae, and/or other pathogens approximately 8 years preceding ultrasound testing. Both case-control and cohort analysis will be stratified by levels of hemostasis and inflammation, including CRP, fibrinogen, Lp(a), and plasminogen- activator inhibitor-1. A separate nested substudy performed on PBMCs, prospectively collected from 80 cases and 80 controls, will examine the host T-cell proliferative response to CMV and other pathogens in relation to disease and also search for a chronic persistent infection with Chlamydia pneumoniae evidence by DNA detection. Thus, this study will assemble a prognostic profile of infectious, inflammatory, and hemostatic factors and provide a foundation for possible future primary prevention trials.