Blood Pressure and Arterial Stiffness in Kenyan Adolescents With a + Thalassemia Anthony O. Etyang, MBChB, MMed, MSc; Christopher Khayeka-Wandabwa, MSc; Sailoki Kapesa, Dip Clin Med & Surg; Esther Muthumbi, MBChB, MSc; Emily Odipo, BSc; Marylene Wamukoya, MPH; Nicholas Ngomi, MPH; Tilahun Haregu, PhD; Catherine Kyobutungi, MBChB, MSc, PhD; Metrine Tendwa, DLT; Johnstone Makale, DLT; Alex Macharia, MSc; J. Kennedy Cruickshank, MBChB, MD, FRCP; Liam Smeeth, PhD, FRCGP, FMedSci; J. Anthony G. Scott, FRCP; Thomas N. Williams, PhD, FRCPCH Background-—Recent studies have discovered that a-globin is expressed in blood vessel walls where it plays a role in regulating vascular tone. We tested the hypothesis that blood pressure (BP) might differ between normal individuals and those with a + thalassemia, in whom the production of a-globin is reduced. Methods and Results-—The study was conducted in Nairobi, Kenya, among 938 adolescents aged 11 to 17 years. Twenty-four- hour ambulatory BP monitoring and arterial stiffness measurements were performed using an arteriograph device. We genotyped for a + thalassemia by polymerase chain reaction. Complete data for analysis were available for 623 subjects; 223 (36%) were heterozygous (Àa/aa) and 47 (8%) were homozygous (Àa/Àa) for a + thalassemia whereas the remaining 353 (55%) were normal (aa/aa). Mean 24-hour systolic BP ÆSD was 118Æ12 mm Hg in aa/aa, 117Æ11 mm Hg in Àa/aa, and 118Æ11 mm Hg in Àa/Àa subjects, respectively. Mean 24-hour diastolic BP ÆSD in these groups was 64Æ8, 63Æ7, and 65Æ8 mm Hg, respectively. Mean pulse wave velocity (PWV)ÆSD was 7Æ0.8, 7Æ0.8, and 7Æ0.7 ms À1 , respectively. No differences were observed in PWV and any of the 24-hour ambulatory BP monitoring-derived measures between those with and without a + thalassemia. Conclusions-—These data suggest that the presence of a + thalassemia does not affect BP and/or arterial stiffness in Kenyan adolescents. ( J Am Heart Assoc. 2017;6: e005613. DOI: 10.1161/JAHA.117.005613.) Key Words: adolescence • ambulatory blood pressure monitoring • a + thalassemia T he thalassemias, in which there is disordered or absent production of the a- or b-globin chains that make up normal hemoglobin, are the most common monogenic disorders of humans. 1 The geographical distribution of a + thalassemia, in which there is deletion of 1 or more of the HBA genes that encode a-globin (Hba) production, closely mirrors that of malaria transmission, 2 and it has been demonstrated that these deletions confer protection against both severe and nonsevere malaria. 2–5 Although it has long been believed that Hba expression is limited to red blood cells, it has recently been demonstrated that Hba is also expressed in mouse endothelial cells where it plays a role in nitric oxide (NO) signaling, influencing vascular smooth muscle tone in resistance arteries. 6,7 A macromolec- ular complex formed by Hba and endothelial nitric oxide synthase (eNOS), regulates NO signaling at myoendothelial junctions. 8 Disruption of this complex lowers blood pressure (BP) in both normotensive and hypertensive mice. 8 It has also been shown that resistance arteries from mice lacking 2 of the 4 a-globin genes (Àa 2 /Àa 2 ) have reduced contractility posttreatment with the vasoconstrictor, phenylephrine. 9 Indi- viduals with a + thalassemia have been shown to have higher microvasculature tortuosity. 10 From the foregoing, it could be expected that individuals with a + thalassemia might have lower BP compared with those with normal hemoglobin. However, the few studies conducted in humans have yielded inconsistent results. Whereas 1 review 11 suggested that a + thalassemic individuals have moderate hypotension, other investigators have found elevated BPs in subjects with this condition. 12,13 These studies were limited by small sample sizes and the failure to use 24-hour ambulatory blood From the KEMRI-Wellcome Trust Research Program, Kilifi, Kenya (A.O.E., S.K., E.M., E.O., M.T., J.M., A.M., J.A.G.S., T.N.W.); London School of Hygiene and Tropical Medicine, London, United Kingdom (A.O.E., L.S., J.A.G.S.); African Population and Health Research Centre, Nairobi, Kenya (C.K.-W., M.W., N.N., T.H., C.K.); King’s College, London, United Kingdom (J.K.C.); Imperial College, London, United Kingdom (T.N.W.). Correspondence to: Anthony O. Etyang, MBChB, MMed, MSc, KEMRI- Wellcome Trust Research Program, Department of Epidemiology and Demog- raphy, PO Box 230, Kilifi, 80108 Kenya. E-mail: aetyang@kemri-wellcome.org Received January 18, 2017; accepted March 1, 2017. ª 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduc- tion in any medium, provided the original work is properly cited. DOI: 10.1161/JAHA.117.005613 Journal of the American Heart Association 1 ORIGINAL RESEARCH