Background . Several investigators have found that Chlamydia pneumoniae and cytomegalovirus infections may be risk factors for coronary heart disease. However, the data remain controversial. To address this hypothesis, data and specimens were collected from a well-established prospective cohort of active-duty personnel from the US military.

Methods . A nested case-control study was conducted with 300 case patients and 300 matched control subjects. Case patients were men (age, 30–50 years) with a medically documented, first-time hospitalization for acute myocardial infarction (MI) and from whom a serum specimen had been drawn ⩾1 year before the time of the acute MI. Population-based control subjects were chosen from the same cohort and were individually matched by age, race, and time of specimen collection. Evidence of past infections with C. pneumoniae and cytomegalovirus were measured by microimmunofluorescence assay and enzyme-linked immunosorbent assay, respectively.

Results . Significant risk was associated with high titer (⩾1 : 64) to C. pneumoniae immunoglobulin A (IgA) (adjusted relative risk [RR_adj], 1.67; 95% confidence interval [CI], 1.04–2.70). This increased risk was greatest when specimens were collected 1–5 years before the event (RR_adj, 2.11; 95% CI, 1.06–4.21). High titer (⩾1 : 256) to C. pneumoniae immunoglobulin G (IgG) was also associated with an elevated risk (RR_adj, 1.74; 95% CI, 0.90–3.34) after full adjustment for cardiovascular risk factors, whereas no independent risk for acute MI was associated with cytomegalovirus IgG seropositivity.

Conclusions . This study demonstrates a significant association between high titers to C. pneumoniae IgG and IgA and acute MI in a cohort of young men and suggests that recent or chronic active infections could be associated with an increased risk for MI.