title: Circulating angiopoietins-1 and -2, angiopoietin receptor Tie-2 and vascular endothelial growth factor-A as biomarkers of acute myocardial infarction: a prospective nested case-control study.
abstract: BACKGROUND
  Angiogenesis is up-regulated in myocardial ischemia. However, limited data exist assessing the value of circulating angiogenic biomarkers in predicting future incidence of acute myocardial infarction (AMI). Our aim was to examine the association between circulating levels of markers of angiogenesis with risk of incident acute myocardial infarction (AMI) in men and women.
  
  
  METHODS
  We performed a case-control study (nested within a large cohort of persons receiving care within Kaiser Permanente of Northern California) including 695 AMI cases and 690 controls individually matched on age, gender and race/ethnicity.
  
  
  RESULTS
  Median [inter-quartile range] serum concentrations of vascular endothelial growth factor-A (VEGF-A; 260 [252] vs. 235 [224] pg/mL; p = 0.01) and angiopoietin-2 (Ang-2; 1.18 [0.66] vs. 1.05 [0.58] ng/mL; p < 0.0001) were significantly higher in AMI cases than in controls. By contrast, endothelium-specific receptor tyrosine kinase (Tie-2; 14.2 [3.7] vs. 14.0 [3.1] ng/mL; p = 0.07) and angiopoietin-1 levels (Ang-1; 33.1 [13.6] vs. 32.5 [12.7] ng/mL; p = 0.52) did not differ significantly by case-control status. After adjustment for educational attainment, hypertension, diabetes, smoking, alcohol consumption, body mass index, LDL-C, HDL-C, triglycerides and C-reactive protein, each increment of 1 unit of Ang-2 as a Z score was associated with 1.17-fold (95 percent confidence interval, 1.02 to 1.35) increased odds of AMI, and the upper quartile of Ang-2, relative to the lowest quartile, was associated with 1.63-fold (95 percent confidence interval, 1.09 to 2.45) increased odds of AMI.
  
  
  CONCLUSIONS
  Our data support a role of Ang-2 as a biomarker of incident AMI independent of traditional risk factors.
authors.affiliation: Kaiser Permanente Division of Research, Oakland, CA 94612, USA. cgi@dor.kaiser.org
authors.forename: Carlos
authors.initials: C
authors.lastname: Iribarren
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Phelps
authors.forename: Jeanne A
authors.initials: JA
authors.lastname: Darbinian
authors.forename: Edward R
authors.initials: ER
authors.lastname: McCluskey
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
authors.forename: Evangelos
authors.initials: E
authors.lastname: Hytopoulos
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Vogelman
authors.forename: Norman
authors.initials: N
authors.lastname: Orentreich
mesh_terms: D000368:Aged; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D006279:Health Maintenance Organizations; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D042787:Receptor, TIE-2 / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2