Published online before print July 25, 2005, doi: 10.1161/01.HYP.0000174988.81829.72
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(Hypertension. 2005;46:527.)
© 2005 American Heart Association, Inc.
Original Articles |
Cardiovascular Risk in Relation to 
-Adducin Gly460Trp Polymorphism and Systolic Pressure
A Prospective Population Study
From the Study Coordinating Centre, Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, University of Leuven, Belgium (Y.L., L.T., T.K., J.A.S); the Division of Nephrology, Dialysis, and Hypertension, University Vita Salute San Raffaele, Milan, Italy (L.Z., G.B.); and the Department of Pharmacology and Toxicology, Cardiovascular Research Institute, Maastricht University, the Netherlands (H.S.-B.).
Correspondence to Jan A. Staessen, MD, PhD, FESC, FAHA, Studiecoördinatiecentrum, Laboratorium Hypertensie, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. E-mail jan.staessen{at}med.kuleuven.be
Preliminary evidence from 1 case-control study suggested that in hypertensive patients, the 
-adducin 460Trp allele might be associated with a 2-fold higher risk of coronary heart disease. In a prospective population study, we investigated whether the -adducin Gly460Trp polymorphism predicted mortality and morbidity. From August 1985 until July 2003, we randomly recruited 2235 Belgian residents. We obtained information on vital status (until July 1, 2004) and the incidence of events via registries and repeat examinations (median 3). In Cox regression, before and after adjustment for other risk factors, we found strong interaction between systolic blood pressure at baseline, analyzed as a continuous variable, and the -adducin polymorphism in relation to total (P=0.01) and cardiovascular mortality (P=0.007) and all cardiovascular (P=0.003), cardiac (P=0.001), and coronary events (P=0.03). The hazard ratio for total mortality associated with the Trp allele relative to GlyGly homozygosity was 2.30 (95% confidence interval, 1.12 to 4.72; P=0.02) in patients with stage-2 systolic hypertension (
160 mm Hg) and 0.88 (0.61 to 1.26; P=0.48) in the other participants. For all cardiovascular complications, these estimates were 2.94 (1.28 to 6.74; P=0.01) and 0.83 (0.58 to 1.20; P=0.32), respectively. For all cardiovascular events, the positive predictive value and the attributable risk associated with the Trp allele in patients with stage-2 systolic hypertension were 76.9% and 44.3%, respectively. In conclusion, the -adducin Gly460Trp polymorphism, in combination with systolic blood pressure, is a strong predictor of cardiovascular mortality and morbidity.
Key Words: genes • epidemiology • morbidity
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