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6 July 1999 | Volume 131 Issue 1 | Pages 7-13
Background: Hyperuricemia is associated with risk for cardiovascular disease and death. However, the role of uric acid independent of established risk factors is uncertain.
Objective: To examine the relation of serum uric acid level to incident coronary heart disease, death from cardiovascular disease, and death from all causes.
Design: Community-based, prospective observational study.
Setting: Framingham, Massachusetts.
Patients: 6763 Framingham Heart Study participants (mean age, 47 years).
Measurements: Serum uric acid level at baseline (1971 to 1976); event rates per 1000 person-years by sex-specific uric acid quintile.
Results: During 117 376 person-years of follow-up, 617 coronary heart disease events, 429 cardiovascular disease deaths, and 1460 deaths from all causes occurred. In men, after adjustment for age, elevated serum uric acid level was not associated with increased risk for an adverse outcome. In women, after adjustment for age, uric acid level was predictive of coronary heart disease (P = 0.002), death from cardiovascular disease (P = 0.009), and death from all causes (P = 0.03). After additional adjustment for cardiovascular disease risk factors, uric acid level was no longer associated with coronary heart disease, death from cardiovascular disease, or death from all causes. In a stepwise Cox model, diuretic use was identified as the covariate responsible for rendering serum uric acid a statistically nonsignificant predictor of outcomes.
Conclusions: These findings indicate that uric acid does not have a causal role in the development of coronary heart disease, death from cardiovascular disease, or death from all causes. Any apparent association with these outcomes is probably due to the association of uric acid level with other risk factors.
Author and Article Information
From the National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts; and Boston University School of Medicine, Boston, Massachusetts.
Grant Support: The Framingham Heart Study is supported by National Institutes of Health/National Heart, Lung, and Blood Institute contract N01-HC-38038. This investigation was supported in part by a research grant from Merck and Co., Inc. Dr. Culleton is a recipient of the 1997-1999 Kidney Foundation of Canada Fellowship.
Requests for Reprints: Daniel Levy, MD, Framingham Heart Study, 5 Thurber Street, Framingham, MA 01702; e-mail, Dan{at}fram.nhlbi.nih.gov.
Current Author Addresses: Dr. Culleton: Division of Nephrology, University of Calgary, Foothills Hospital, Room C-210, 1403 29th Street, Calgary, Alberta T2N 2T9, Canada.
Drs. Larson, Kannel, and Levy: Framingham Heart Study, 5 Thurber Street, Framingham, MA 01702. ARTICLE
Serum Uric Acid and Risk for Cardiovascular Disease and Death: The Framingham Heart Study
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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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|
|
 |
|
 H. Janssens, E. van de Lisdonk, H Bor, H. van den Hoogen, and M Janssen Gout, just a nasty event or a cardiovascular signal? A study from primary care Fam. Pract., August 1, 2003; 20(4): 413 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 K. T. Rott and C. A. Agudelo Gout JAMA, June 4, 2003; 289(21): 2857 - 2860. [Full Text] [PDF]
|
|
|
|
 |
|
 T Bardin Fenofibrate and losartan Ann Rheum Dis, June 1, 2003; 62(6): 497 - 498. [Full Text] [PDF]
|
|
|
|
|
|
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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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|
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