title: EN-RAGE: a novel inflammatory marker for incident coronary heart disease.
abstract: OBJECTIVE
  Inflammation plays a key role in atherosclerosis. We hypothesized that novel inflammatory markers may predict the risk of coronary heart disease (CHD).
  
  
  RESULTS
  We investigated the association of 16 inflammatory biomarkers with the risk of CHD in a random subset of 839 CHD-free individuals in a prospective population-based cohort study. A Bonferroni corrected P value of 3.1×10(-3) was used as a threshold of statistical significance. The mean age at baseline was 72.8 years. During a median follow-up of 10.6 years, 99 cases of incident CHD were observed. Among all inflammatory biomarkers, neutrophil-derived human s100a12 (extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE]) showed the strongest association with the risk of CHD (P value 2.0×10(-3)). After multivariable adjustment for established cardiovascular risk factors, each standard deviation increase in the natural log-transformed EN-RAGE was associated with 30% higher risk of incident CHD (hazard ratio, 1.30; 95% confidence interval, 1.06-1.59). Further adjustment for previously studied inflammatory markers did not attenuate the association. Excluding individuals with prevalent type 2 diabetes mellitus, impaired kidney function, or individuals using antihypertensive medication did not change the effect estimates. Cause-specific hazard ratios suggested a stronger association between EN-RAGE and CHD mortality compared with stable CHD.
  
  
  CONCLUSIONS
  Our results highlight EN-RAGE as an inflammatory marker for future CHD in a general population, beyond traditional CHD risk factors and inflammatory markers.
authors.affiliation: From the Department of Epidemiology (S.L., S.S., M.A.I., A.H., O.H.F., A.D.), Department of Neurology (M.A.I.), and Department of Radiology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Symen
authors.initials: S
authors.lastname: Ligthart
authors.affiliation: From the Department of Epidemiology (S.L., S.S., M.A.I., A.H., O.H.F., A.D.), Department of Neurology (M.A.I.), and Department of Radiology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Sedaghat
authors.affiliation: From the Department of Epidemiology (S.L., S.S., M.A.I., A.H., O.H.F., A.D.), Department of Neurology (M.A.I.), and Department of Radiology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: From the Department of Epidemiology (S.L., S.S., M.A.I., A.H., O.H.F., A.D.), Department of Neurology (M.A.I.), and Department of Radiology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: From the Department of Epidemiology (S.L., S.S., M.A.I., A.H., O.H.F., A.D.), Department of Neurology (M.A.I.), and Department of Radiology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: From the Department of Epidemiology (S.L., S.S., M.A.I., A.H., O.H.F., A.D.), Department of Neurology (M.A.I.), and Department of Radiology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology / Q000401:mortality; D005260:Female; D006801:Humans; D015994:Incidence; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D009426:Netherlands / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D009418:S100 Proteins / Q000097:blood*; D000067616:S100A12 Protein
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human
keywords: biomarker; coronary artery disease; cytokines; inflammation