Association between antibodies to heat shock protein 65 and coronary atherosclerosis. Possible mechanism of action of Helicobacter pylori and other bacterial infections in increasing cardiovascular risk.

INTRODUCTION: There is growing evidence that the immune response is involved in atherosclerosis. Antibodies to heat shock protein 60/65 have been shown to be a risk factor for carotid atherosclerosis and been proposed as a diagnostic marker of atherosclerosis. In addition, it has been suggested that the immune response to heat shock protein 60/65 may be a link between exposure to microorganisms and increased cardiovascular risk.

AIMS: (1) To investigate the association between anti-shock protein 65 titre and coronary atherosclerosis. (2) To assess whether anti-mhsp65 titre is a useful diagnostic marker of atherosclerosis; (3) To examine the influence of Helicobacter pylori infection on anti-heat shock protein 65 titre.

METHODS AND RESULTS: In the first study we measured anti-heat shock protein 65 titres in 136 consecutive male subjects admitted for routine coronary angiography. Anti-heat shock protein 65 titres correlated with both the severity and extent of coronary atherosclerosis and the relationship remains statistically significant for the presence of atherosclerosis (P = 0.012) after adjustment for possible confounding influences. However the association had insufficient sensitivity to be a useful clinical test. In the second study we recruited 100 patients with confirmed active H. pylori infection and double blindly randomized them to eradication therapy or placebo. Successful eradication of H. pylori led to a significant fall in anti-heat shock protein 65 titres (from a mean of 256.4 AU.ml-1 to 137.5 AU. ml-1. P = 0.033).

CONCLUSION: These results raise the possibility that exposure to H. pylori and other micro-organisms lead to an increased risk of clinically manifest coronary artery disease by an autoimmune process.