(Hypertension. 1999;34:144-150.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Serum Uric Acid and Cardiovascular Events in Successfully Treated Hypertensive Patients
From the Department of Epidemiology and Social Medicine (M.H.A., H.C., S.M.), Albert Einstein College of Medicine, Bronx, NY; and Merck & Co (S.K), West Point, Pa.
Correspondence to Michael H. Alderman, MD, Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Room 1311, Belfer ECHS, Bronx, NY 10461.
Abstract—To determine whether pretreatment and/or in-treatment serum uric acid (SUA) is independently and specifically associated with cardiovascular events in hypertensive patients, we examined the 20-year experience of 7978 mild-to-moderate hypertensive participants in a systematic worksite treatment program. Clinical evaluation and treatment were protocol-directed. SUA was measured at entry and annually thereafter. Subjects were stratified according to gender-specific quartile of baseline SUA. Blood pressures at entry and in-treatment were, respectively, 152.5/95.6 and 138.9/85.4 mm Hg. SUA was normally distributed with a mean of 0.399±0.0893 and 0.321±0.0833 mmol/L for men and women, respectively. Subjects with highest SUA were heavier, had greater evidence of cardiovascular disease (CVD), higher systolic blood pressure, higher creatinine, more frequent diuretic use, and lower prevalence of diabetes. During an average follow-up of 6.6 years (52 751 patient-years), 548 CVD events (183 mortal) and 116 non-CVD events occurred. In bivariate analysis, the association of SUA to CVD was more robust in nonwhites than whites and in patients at low versus high CVD risk. In multivariate analysis, CVD incidence was significantly associated with SUA with a hazard ratio of 1.22 (95% confidence interval 1.11 to 1.35), controlling for other known cardiovascular risk factors, including serum creatinine, body mass index, and diuretic use. Despite blood pressure control, SUA levels increased during treatment and were significantly and directly associated with CVD events, independently of diuretic use and other cardiovascular risk factors.
Key Words: uric acid, serum • blood pressure • cardiovascular disease • hypertension, essential
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
M. H. Alderman Serum Uric Acid and Cardiovascular Disease Risk Ann Intern Med, April 4, 2000; 132(7): 591 - 591. [Full Text] [PDF]
|
|
|
|
|
|
R. J. Johnson, K. R. Tuttle, B. Culleton, and D. Levy Much Ado About Nothing, or Much to Do About Something? The Continuing Controversy Over the Role of Uric Acid in Cardiovascular Disease Hypertension, March 1, 2000; 35 (3): e10 - e10. [Full Text]
|
|
|
|
|
|
P. August Hypertension in Men J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3451 - 3454. [Full Text] [PDF]
|
|
|
|
 |
|
 Is Uric Acid a Real Cardiovascular Risk Factor? Journal Watch Cardiology, September 16, 1999; 1999(916): 12 - 12. [Full Text]
|
|
|
|
 |
|
 M. Mazzali, J. Kanellis, L. Han, L. Feng, Y.-Y. Xia, Q. Chen, D.-H. Kang, K. L. Gordon, S. Watanabe, T. Nakagawa, et al. Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism Am J Physiol Renal Physiol, June 1, 2002; 282(6): F991 - F997. [Abstract] [Full Text] [PDF]
|
|