Ethnic/racial differences in circulating markers of angiogenesis and their association with cardiovascular risk factors and cardiovascular disease Philip C. Bennett a, b , Paramjit S. Gill c, 1 , Stanley Silverman b , Andrew D. Blann a , Balu Balakrishnan a , Gregory Y.H. Lip a, ⁎ , 1 a University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, B18 7QH, United Kingdom b Department of Vascular Surgery, City Hospital, Birmingham, B18 7QH, United Kingdom c Primary Care Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, England, United Kingdom abstract article info Article history: Received 12 January 2012 Accepted 17 March 2012 Available online xxxx Keywords: Ethnic differences Angoipoietin-1 Angiopoietin-2 Soluble Tie-2 receptor Angiogenin Cardiovascular risk factors Objective: To determine (a) whether ethnic/racial differences exist in circulating markers of angiogenesis (Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), soluble Tie-2 receptor (sTie-2) and Angiogenin) between South Asian (SA; from India, Pakistan and Bangladesh); Black African-Caribbean and White (W) ethnic groups, and (b) associations between these markers in stable cardiovascular disease (CVD) and its risk factors. Patients and methods: We recruited 243 subjects (82 SA, 84 Black and 77 W) with symptomatic and clinically confirmed CVD (n = 108), risk factor controls (with ≥1 cardiovascular risk factor, e.g. smoking, diabetes mel- litus, dyslipidaemia, hypertension) and with ankle brachial pressure index > 1) (n = 64) and healthy controls free of CVD and risk factors (n = 56). Angiogenic markers were measured by enzyme linked immunoassay. Results: In healthy controls, angiogenin was higher in SA and Black subjects, compared to Whites (p b 0.05). sTie-2 correlated inversely with angiogenin (p = 0.001), was higher in women (p = 0.029) and was lower in smokers (p = 0.007). Overall, age (p = 0.001) was the only independent factor associated with angiopoietin-1. Angiogenin (p = 0.01) and SBP (p = 0.014) were both independently higher in the Black group compared to the White group. Conclusions: Ethnic, racial, and demographic differences are evident in certain circulating markers of angio- genesis. With the exception of an effect of smoking on sTie-2, these differences are not influenced by the presence of other risk factors, nor the presence of stable cardiovascular disease. © 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Cardiovascular disease, manifesting as peripheral arterial disease, coronary artery disease or cerebrovascular disease, is an important consequence of atherosclerosis. Angiogenesis, the formation of new blood vessels, is evident in these conditions and is closely related to atherogenesis, thrombogenesis and the development of intra-plaque vasa vasorum [1,2]. Furthermore, angiogenesis is a feature of disease development and progression [3,4], and is especially frequent in ad- vanced cardiovascular disease and may characterise atherosclerotic lesions at high risk of haemorrhage or rupture [4–6]. Vascular endo- thelial growth factor (VEGF), acting on the endothelium, is one of the major growth factors driving angiogenesis, and raised plasma levels in diabetes, peripheral artery disease and coronary artery dis- ease is evidence of this increased angiogenic activity [7]. In addition to VEGF, the angiopoietins (Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are additional angiogenic growth factors that are specific for endothelium. Ang-1 and Ang-2 play modulatory roles by binding a common receptor, the endothelial cell-specific tyrosine kinase receptor Tie-2 [8,9], a soluble form of which (i.e. sTie-2) can be detected in plasma. Together, the angiopoietins regulate endothelial cell differentiation: Ang-1 accelerates the maturation of the blood ves- sel, whilst Ang-2, an antagonist of Ang-1, destabilises the vessel and de- grades the basal lamina [10,11]. Plasma levels of Ang-1 and Ang-2 levels are abnormal in, and are associated with, cardiovascular risk in patients with cardiovascular disease [12] and also in other manifestations of atherosclerosis, including heart failure, acute coronary syndromes and hypertension [8,13–17]. Angiogenin is a small polypeptide implicated in angiogenesis normally found in the vasculature, but also in some physiological and pathological conditions, including peripheral and coronary athero- sclerosis [18–20]. Elevated angiogenin levels have been found to be higher in those with severe peripheral atherosclerosis, compared to mild and moderate disease [19], and raised levels in acute coronary syndromes predict a poor outcome at six months [20]. Thus, angiogenin International Journal of Cardiology xxx (2012) xxx–xxx ⁎ Corresponding author. Tel.: + 44 121507 5080; fax: + 44 121 5544083. E-mail address: g.y.h.lip@bham.ac.uk (G.Y.H. Lip). 1 These authors contributed equally to this work. IJCA-14647; No of Pages 4 0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2012.03.158 Contents lists available at SciVerse ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard Please cite this article as: Bennett PC, et al, Ethnic/racial differences in circulating markers of angiogenesis and their association with cardio- vascular risk factors and cardiovascular disease, Int J Cardiol (2012), doi:10.1016/j.ijcard.2012.03.158