Open Access Highly Accessed Research article

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

Carlos Iribarren1*, Bruce H Phelps2, Jeanne A Darbinian1, Edward R McCluskey2, Charles P Quesenberry1, Evangelos Hytopoulos2, Joseph H Vogelman3 and Norman Orentreich3

Author Affiliations

1 Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612, USA

2 Aviir, Inc., 2463 Faber Place, Palo Alto, CA 94303, USA

3 Orentreich Foundation for the Advancement of Science, Inc., 855 Route 301, Cold Spring-on-Hudson, NY 10516, USA

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BMC Cardiovascular Disorders 2011, 11:31  doi:10.1186/1471-2261-11-31

Published: 14 June 2011



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.


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.


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.


Our data support a role of Ang-2 as a biomarker of incident AMI independent of traditional risk factors.

angiogenesis; acute myocardial infarction; epidemiology