title: Multimarker approach predicts adverse cardiovascular events in women evaluated for suspected ischemia: results from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation.
abstract: BACKGROUND
  Inflammatory marker and hemoglobin levels (eg biomarkers) considered separately, predict adverse events in selected populations.
  
  
  OBJECTIVE
  A multiple biomarker approach predicts adverse events in women referred for evaluation of ischemia.
  
  
  METHODS
  We investigated associations between biomarkers (high sensitivity C-reactive protein, interleukin-6, serum amyloid-A, and hemoglobin levels) with adverse outcomes in women referred for coronary angiography for suspected ischemia in the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE).
  
  
  RESULTS
  Among 595 women (mean age 58 years, ejection fraction [EF] 65%, majority without coronary stenosis >or= 50%) followed for 3.6 +/- 1.8 years (mean +/- SD), those without abnormal markers had fewer events (11.6%) compared to those with 1 (18.4%), 2 (20.9%), or 3 (37%) abnormal markers (p < 0.001 for trend). Women without abnormal markers had fewer deaths (1.6%) than women with 1 (6.1%), 2 (9.1%), or 3 (17%) abnormal markers (p < 0.001 for trend). Adding low hemoglobin was associated with higher adverse event and all-cause mortality rates. In multivariate analysis, as the number of abnormal biomarkers increased risk increased. Women with 3 or 4 abnormal biomarkers were approximately 10-20 times more likely to die (p < 0.05). Biomarkers added to the predictive information provided by the Framingham Risk Score.
  
  
  CONCLUSIONS
  Among women undergoing coronary angiography for suspected ischemia, a multibiomarker approach predicted adverse events. Biomarkers added prognostic information beyond that obtained from traditional risk factors.
authors.affiliation: Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Arant
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Wessel
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: Marian B
authors.initials: MB
authors.lastname: Olson
authors.forename: Steven E
authors.initials: SE
authors.lastname: Reis
authors.forename: B
authors.initials: B
authors.lastname: Delia Johnson
authors.forename: Barry L
authors.initials: BL
authors.lastname: Sharaf
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Pauly
authors.forename: Eileen
authors.initials: E
authors.lastname: Handberg
authors.forename: Issam
authors.initials: I
authors.lastname: Zineh
authors.forename: George
authors.initials: G
authors.lastname: Sopko
authors.forename: Sheryl F
authors.initials: SF
authors.lastname: Kelsey
authors.forename: C
authors.initials: C
authors.lastname: Noel Bairey Merz
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D016001:Confidence Intervals; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D015999:Multivariate Analysis; D017202:Myocardial Ischemia / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D054555:National Heart, Lung, and Blood Institute (U.S.); D011379:Prognosis; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000032:analysis; D012737:Sex Factors; D013318:Stroke Volume; D013577:Syndrome; D014481:United States / Q000453:epidemiology; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D015850:Interleukin-6; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein