title: Differential expression of chemokines, risk of stable coronary heart disease, and correlation with established cardiovascular risk markers.
abstract: OBJECTIVE
  We investigated the association of several chemokines with the risk of stable coronary heart disease (CHD) in a large case-control study after adjustment for other established risk factors. Furthermore, we analyzed their correlation with various acute-phase proteins, inflammation-associated cytokines, and an adhesion molecule.
  
  
  RESULTS
  We included 312 patients aged 40 to 68 years with angiographically confirmed and stable CHD and 472 age- and gender-matched controls in this study. The main outcome measure was the odds ratio (OR) for CHD associated with increased levels of interferon (INF)-inducible protein of 10 kd (IP-10), interleukin (IL)-8, regulated on activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammation protein 1alpha (MIP-1alpha), or eotaxin determined by rigidly evaluated sandwich ELISAs. Serum levels of IP-10 and IL-8 were higher, and serum levels of RANTES were lower in CHD patients when compared with age- and gender-matched controls. In addition, values in the second and top tertile of IP-10 and IL-8 were associated with an increased OR for CHD when compared with values in the bottom tertile [OR for IP-10 (top tertile) was 2.62 (95% CI, 1.79 to 3.85) in the age- and gender-adjusted model and 1.93 (95% CI, 1.23 to 3.04) in the fully adjusted model, and for IL-8, the OR was 1.77 (95% CI, 1.20 to 2.59) and 1.53 (95% CI, 0.98 to 2.39), respectively]; increased RANTES values were associated with a lower OR for CHD [OR, 0.67 (95% CI, 0.47 to 0.96) and 0.61 (95% CI, 0.40 to 0.94)]. Furthermore, positive correlations of IP-10 and IL-8 with several acute-phase proteins or inflammation-associated cytokines were evident, and positive correlations for IP-10 plasma viscosity and intercellular adhesion molecule 1 were also present.
  
  
  CONCLUSIONS
  The current study suggests that there may be no universal upregulation of chemokines in CHD-associated inflammation but different upregulation of IP-10 and IL-8 versus downregulation of RANTES; there was no clear disease association for MCP-1, MIP-1alpha, or eotaxin.
authors.affiliation: Department of Epidemiology, The German Centre for Research on Ageing, University of Heidelberg, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Rothenbacher
authors.forename: Sylvia
authors.initials: S
authors.lastname: Müller-Scholze
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Hubert
authors.initials: H
authors.lastname: Kolb
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000097:blood; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000097:blood; D054357:Chemokine CXCL10; D018925:Chemokines / Q000097:blood*; D019742:Chemokines, CC / Q000097:blood; D019743:Chemokines, CXC / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000453:epidemiology* / Q000276:immunology*; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology* / Q000276:immunology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D019402:Macrophage Inflammatory Proteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D015854:Up-Regulation / Q000276:immunology; D014657:Vasculitis / Q000097:blood / Q000453:epidemiology / Q000276:immunology
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C515456:CCL11 protein, human; C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D018799:Intercellular Adhesion Molecule-1