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

• Published in: BMC cardiovascular disorders Vol. 11; no. 1; p. 31
• Main Authors: Iribarren, Carlos, Phelps, Bruce H, Darbinian, Jeanne A, McCluskey, Edward R, Quesenberry, Charles P, Hytopoulos, Evangelos, Vogelman, Joseph H, Orentreich, Norman
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.06.2011; BioMed Central; BMC
• Subjects: acute myocardial infarction; Aged; angiogenesis; Angiopoietin-1 - blood; Angiopoietin-2 - blood; Biological markers; Biomarkers - blood; California - epidemiology; Care and treatment; Case-Control Studies; Cell receptors; Chi-Square Distribution; Diagnosis; epidemiology; Female; Health Maintenance Organizations; Heart attack; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction - blood; Myocardial Infarction - epidemiology; Myocardial Infarction - physiopathology; Neovascularization; Neovascularization, Physiologic; Odds Ratio; Physiological aspects; Predictive Value of Tests; Prognosis; Prospective Studies; Receptor, TIE-2 - blood; Risk Assessment; Risk Factors; Time Factors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - blood; California; United States
• ISSN: 1471-2261; 1471-2261
• DOI: 10.1186/1471-2261-11-31

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.