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Abstract
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.
Acknowledgements
We acknowledge the support of the Sandwell and West Birmingham Hospitals NHS Trust Research and Development programme for the Haemostasis Thrombosis and Vascular Biology Unit. We thank Professor DG Beevers, Dr C Spencer, Dr S Nadar and Dr D Felmeden for help with data collection. Other ASCOT Investigators are listed in reference Citation19.