Prevalence of intimal pathogen burden in acute coronary syndromes

Increasing evidence supports a link between serological evidence of prior exposure to infectious pathogens, pathogen burden, and the risk for future myocardial infarction and death in patients with coronary artery disease. Based on this concept, we evaluated the intimal presence of four pathogens in human coronary atheroma, clinically associated with acute coronary syndromes (ACS) and stable angina (SA), and the effect of pathogen burden on the expression of human heat-shock protein 60 (hHSP60), a key protein in (auto-)immune pathogenesis of atherosclerosis. Coronary atherectomy specimens retrieved from 53 primary target lesions of patients with ACS (n = 33) or SA (n = 20) were assessed immunohistochemically for the presence of Chlamydia pneumoniae (C.pn.), Helicobacter pylori (H. p.), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV), and for the expression of hHSP60. Chlamydia pneumoniae-was present in 74%, Helicobacter pylori in 32%, CMV in 13% and EBV in 42%. Exclusively C. pn. revealed a prevalence in ACS (91%) vs SA (45%; p < 0.001). Immunohistochemical analysis revealed 6 lesions without, 21 lesions with 1, 17 lesions with 2, 6 lesions with 3 and 3 lesions with 4 infectious agents. As an important finding, the mean value in ACS lesions was significantly increased compared to those in SA (1.9 vs 1.1; p < 0.01). ACS-subgroup analysis revealed the highest mean value in patients with pain at rest within the last two days (Braunwald class III). In addition, expression of hHSP60 was significantly higher in ACS (8.7%) compared to SA (1.3%; p < 0.001). Pathogen burden correlated highly significant (p < 0.01) with the expression of hHSP60 (r = 0.44). Our data demonstrate the impact of intimal pathogen burden in plaque instability, and suggest the presence of (auto-)immunoreactions against upregulated hHSP60 as an important pathomechanism that may contribute to acute coronary syndromes.