Published Online
on October 23, 2006

A more recent version of this article appeared on December 1, 2006

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Submitted on June 22, 2006
Revised on July 7, 2006

Uric Acid and the Development of Hypertension. The Normative Aging Study

Todd S. Perlstein; Olga Gumieniak; Gordon H. Williams; David Sparrow; Pantel S. Vokonas; Michael Gaziano; Scott T. Weiss; and Augusto A. Litonjua^*

From the Divisions of Endocrinology, Diabetes, and Hypertension (T.S.P., O.G., G.H.W.) and Aging (M.G.) and Channing Laboratory (S.T.W., A.A.L.), Department of Medicine, Brigham and Women’s Hospital, Boston, Mass; Veterans Administration Boston Healthcare System (D.S., P.S.V., M.G., A.A.L.), Mass; the Department of Medicine (D.S., P.S.V.), Boston University School of Medicine, Mass; and Harvard Medical School (T.S.P., O.G., G.H.W., S.T.W., A.A.L.), Boston, Mass.

^* To whom correspondence should be addressed. E-mail: reaal{at}channing.harvard.edu.

Abstract--Experimental evidence supports a causative role for uric acid in the pathogenesis of hypertension. Prospective studies have variably adjusted for relevant confounders and have been of relatively limited duration. We prospectively examined the relationship between uric acid level and the development of hypertension in the Normative Aging Study, a longitudinal cohort of healthy adult men. Of the 2280 initial men in the Normative Aging Study, 2062 had available information for inclusion in the analysis. Cox proportional hazards model was used to examine the relationship between baseline serum uric acid level and the development of hypertension adjusting for age, body mass index, abdominal circumference, smoking, alcohol, plasma triglycerides, total cholesterol, and plasma glucose. A total of 892 men developed hypertension over a mean of 21.5 years of follow-up. Serum uric acid level independently predicted the development of hypertension in age-adjusted (relative risk [RR]: 1.10; 95% CI: 1.06 to 1.15: P<0.001) and multivariable (RR: 1.05; 95% CI: 1.01 to 1.10; P=0.02) models. Among 1277 men at risk for the development of hypertension at the time of their first serum creatinine measurement, 508 (39.8%) developed hypertension over a mean of 10.3±5.5 years of follow-up. Additionally adjusting for calculated glomerular filtration rate in this subset, serum uric acid remained associated with the development of hypertension (RR: 1.06; 95% CI: 1.01 to 1.12; P=0.03). The baseline serum uric acid level is a durable marker of risk for the development of hypertension. The association is independent of elements of the metabolic syndrome, alcohol intake, and renal function.

Key words: uric acid • hypertension • renal function • prospective studies • aging

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