ReviewChronic infections and coronary heart disease: is there a link?
Section snippets
Review methods
Epidemiological and clinical studies published in any language before January, 1997, that reported on associations between the presence of H pylori, C pneumoniae, or CMV and CHD were sought by Medline searches, scanning of relevant reference lists, hand-searching of cardiology, gastroenterology, and other relevant journals, and discussions with various investigators. Combinations of key words were used in the computer searches, including: Helicobacter pylori, Campylobacter pylori, Chlamydia
Epidemiological associations
Since the first report in 1994, at least 20 epidemiological studies of about 2600 cases in total have reported on the association of H pylori antibody titres and either CHD (19 studies) or stroke (Figure 2). The chief difficulty in trying to find out whether a causal association exists is that certain potential confounding factors; of which low socioeconomic status is a general indicator, seem to be strongly associated both with H pylori infection and with CHD (table).
Failure to make
Epidemiological associations
Most of the 18 published epidemiological studies of C pneumoniae antibodies and CHD (or, in two cases, cerebrovascular disease) found at least two-fold or larger odds ratios (figure 3), and some reported increasing odds ratios with increasing antibody titres. The studies were done in different populations, used different criteria for cases, adjusted for potential confounders to differing degrees, and were, therefore, prone to different biases. The general consistency of their findings in a
Epidemiological associations
Two-fold or larger odds ratios have been reported in several epidemiological studies of CMV antibodies and cardiovascular disease (figure 4). Some of these reports described increasing odds ratios with increasing antibody titres or with the severity of the atherosclerosis, which strengthen the plausibility of the associations. However, these studies of CMV, even more than those of H pylori or C pneumoniae, were characterised by small sample sizes, incomplete adjustments for known confounders,
Observational studies
Epidemiological studies of infections and CHD are needed. These studies should be large enough for moderate-sized effects to be assessed or refuted reliably, and involve repeated antibody measurements in at least a subsample to allow correction for regression dilution.3 In such studies, the effects of residual confounders need to be kept to a minimum, for example by investigation of socially homogeneous populations (such as doctors) or age-matched and sex-matched sibling-pairs (one with and one
Conclusion
The available evidence about chronic infections and CHD is still sparse and its interpretation is limited by potential biases. For H pylori, residual confounding by causal risk factors may account entirely for the rather weak epidemiological associations that have been reported. For C pneumoniae, the evidence of association is stronger, but the temporal sequence of infection and CHD is uncertain. For CMV, only a limited number of patients with classic atherosclerotic CHD have been studied. Some
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