Angiopoietin-2 levels as a biomarker of cardiovascular risk in patients with hypertension.
BACKGROUND
Abnormal angiogenesis is a pathophysiological component of cardiovascular disease (CVD), where circulating biomarkers of angiogenesis are associated with increased CVD risk in hypertension. We hypothesized that raised levels of angiopoietin (Ang)-1 and -2 would predict events in patients with hypertension treated for CVD.


METHODS
We measured angiopoietin levels by enzyme-linked immunosorbent assay (ELISA) in 251 hypertensive participants (85% male; mean age 63.5 years; 192 free of previous CVD events). Plasma angiopoietin levels were related to the subsequent CVD events over a mean follow-up period of 57.1 (SD 11) months.


RESULTS
There were 11 cases of myocardial infarction (MI) and 18 cases of stroke during follow-up. Ang-2 was a significant predictor of MI, stroke, and composite CVD events, with the greatest event-free survival amongst those in the lower tertile (all P<0.05). Ang-1 was not predictive of CVD outcomes. Of CVD risk factors at recruitment (blood pressure, body mass index, plasma glucose, serum and high-density lipoprotein (HDL)-cholesterol), Ang-2 was the only discriminator of incident MI (area under curve (AUC) = 73%, P = 0.013), where a value >4.3 ng/mL optimized specificity and sensitivity. On Cox regression analysis (CVD treatments and risk factors), raised Ang-2 was an independent predictor of MI, P<0.05, but not stroke or composite outcomes.


CONCLUSIONS
Among patients with hypertension, raised levels of Ang-2 were predictive of MI, and further study is warranted to evaluate the use of this biomarker in CVD management, risk stratification, and prevention.
Patel
Jeetesh V
JV
University Department of Medicine, City Hospital, Birmingham, UK.
Lim
Hoong Sern
HS
Varughese
George I
GI
Hughes
Elizabeth A
EA
Lip
Gregory Y H
GY
D000368:Aged; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D019540:Area Under Curve; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D020521:Stroke / Q000175:diagnosis / Q000503:physiopathology; D016019:Survival Analysis
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers