Association of circulating Chlamydia pneumoniae DNA with cardiovascular disease: a systematic review

Abstract

Background: Chlamydia pneumoniae antigens, nucleic acids, or intact organisms have been detected in human atheroma. However, the presence of antibody does not predict subsequent cardiovascular (CV) events. We performed a systematic review to determine whether the detection of C. pneumoniae DNA in peripheral blood mononuclear cells (PBMC) was associated with CV disease.

Methods: We sought studies of C. pneumoniae DNA detection in PBMC by polymerase chain reaction (PCR) among patients with CV disease or other clinical conditions. We pooled studies in which CV patients were compared with non-diseased controls. We analyzed differences between studies by meta-regression, to determine which epidemiological and technical characteristics were associated with higher prevalence.

Results: Eighteen relevant studies were identified. In nine CV studies with control subjects, the prevalence of circulating C. pneumoniae DNA was 252 of 1763 (14.3%) CV patients and 74 of 874 (8.5%) controls, for a pooled odds ratio of 2.03 (95% CI: 1.34, 3.08, P < 0.001). Prevalence was not adjusted for CV risk factors. Current smoking status, season, and age were associated with C. pneumoniae DNA detection. High prevalence (>40%) was found in patients with cardiac, vascular, chronic respiratory, or renal disease, and in blood donors. Substantial differences between studies were identified in methods of sampling, extraction, and PCR targets.

Conclusions: C. pneumoniae DNA detection was associated with CV disease in unadjusted case-control studies. However, adjustment for potentially confounding measures such as smoking or season, and standardization of laboratory methods, are needed to confirm this association.

Figure 1

Meta-analysis of circulating Chlamydia pneumoniae DNA detection in cardiovascular studies with controls. Odds ratios with 95% confidence intervals and pooled odds ratios calculated under a random effects model (Review Manager 4.04).

Figure 2

Funnel plot of Chlamydia pneumoniae DNA detection (Review Manager 4.04). Precision of estimate (reciprocal of standard error) versus odds ratio for studies of circulating C. pneumoniae DNA detection by cardiovascular disease status compared with disease-free controls. The dotted line indicates the pooled odds ratio of the studies at 2.0. The curve illustrates a funnel plot centred about the most precise study, in which an equal number of studies are expected in the left and right tails. Asymmetry of the funnel plot suggests publication bias, or bias in selection of cases or controls.