title: Chlamydia pneumoniae, heat shock proteins 60 and risk of secondary cardiovascular events in patients with coronary heart disease under special consideration of diabetes: a prospective study.
abstract: BACKGROUND
  There have been suggestions of an association between Chlamydia pneumoniae, chlamydial heat shock protein (Ch-hsp) 60 and human heat shock protein (h-hsp) 60 infection sero-status and development of secondary cardiovascular events. Patients with diabetes might be at higher risk since they are prone to infections. The objective of this study was to investigate prospectively the role of Chlamydia pneumoniae (CP), chlamydial heat shock protein (Ch-hsp) 60 and a possible intermediate role of human heat shock protein (h-hsp) 60 sero-status in the development of secondary cardiovascular disease (CVD) events in patients with coronary heart disease (CHD) under special consideration of diabetes mellitus.
  
  
  METHODS
  Patients aged 30-70 undergoing an in-patient rehabilitation program after acute manifestation of coronary heart disease (International Classification of Disease, 9th Rev. pos. 410-414) between January 1999 and May 2000 in one of two participating rehabilitation clinics in Germany were included in this analysis. Chlamydia pneumoniae (CP), chlamydial heat shock protein (Ch-hsp) 60 and human heat shock protein (h-hsp) 60 status at baseline were measured by serum immunoglobulin G and A antibodies. Secondary CVD events (myocardial infarction, stroke, and cardiovascular death) were recorded during a mean follow-up period of 33.5 months (response = 87%).
  
  
  RESULTS
  Among the 1052 subjects 37.4% and 39.3% were sero-positive to CP IgA and IgG respectively, 22.2% were sero-positive to Ch-hsp 60 IgG and 8.4% were positive to h-hsp 60 IgG at baseline. During follow-up, secondary CVD events occurred among 71 (6.8%) participants. Occurrence of a secondary CVD event was more common among CP (IgA) and CP (IgG) sero-positive than among sero-negative patients (p-values 0.04 and 0.1, respectively). The risk of secondary CVD events was increased among patients with both a positive CP sero-status and diabetes compared to infection negative, non-diabetic patients and in general, sero-positivity added a hazard to diabetes. The interaction term between infection sero-status and diabetes was not statistically significant. We were not able to show an intermediate role of human heat shock protein (h-hsp) 60 sero-status in the development of secondary CVD events in patients with CHD.
  
  
  CONCLUSIONS
  Results from this cohort of 1052 patients with pre-existing CHD cannot exclude a possible moderate increase in risk of secondary CVD events among patients with a positive infection sero-status. However, our study showed no intermediate role of human heat shock protein (h-hsp) 60 sero-status in the development of secondary CVD events in patients with CHD. Larger studies or meta-analysis of multiple studies are needed to address the interaction between infection sero-status and diabetes with adequate power.
authors.affiliation: Department of Epidemiology, German Centre for Research on Ageing, University of Heidelberg, Heidelberg, Germany. m.guech-ongey@dkfz-heidelberg.de
authors.forename: Mercy
authors.initials: M
authors.lastname: Guech-Ongey
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.forename: Dorothee
authors.initials: D
authors.lastname: Twardella
authors.forename: Dietrich
authors.initials: D
authors.lastname: Rothenbacher
mesh_terms: D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000209:etiology*; D018834:Chaperonin 60 / Q000097:blood*; D023521:Chlamydophila Infections / Q000150:complications*; D016993:Chlamydophila pneumoniae; D003327:Coronary Disease / Q000097:blood / Q000150:complications* / Q000382:microbiology; D006801:Humans; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000907:Antibodies, Bacterial; D018834:Chaperonin 60; D002097:C-Reactive Protein