Background: Uric acid is a nontraditional risk factor implicated in the development of coronary artery disease (CAD). This study prospectively evaluated the predictive value of serum uric acid (SUA) levels for mortality after angiographic diagnosis of CAD. Methods: Blood samples were collected from 1,595 consecutive, consenting patients with significant, angiographically defined CAD (stenosis 70%). Baseline and procedural variables were recorded and levels of SUA were measured. Patients were followed to death or to the time of contact (mean 2.6 years, range 1.8–5.0 years). Results: Patients averaged 65 ± 11 years of age, 78% were male and 170 subjects died during the follow-up period. In univariate analysis of prospectively defined quintiles, SUA predicted all-cause mortality (fifth quintile vs. first four quintiles: hazard ratio 1.9, p < 0.001). In multivariable Cox regression controlling for 20 covariables, independent predictive value for mortality was retained by SUA (hazard ratio 1.5, confidence interval 1.02–2.1, p = 0.04). In subgroup analysis based on diuretic use status, SUA independently predicted mortality among patients not using diuretics, while SUA was not a significant predictor of mortality among those who used diuretics. Conclusions: In patients with significant, angiographically defined CAD, SUA predicted mortality independent of traditional risk factors. This suggests that elevated SUA may be a risk factor for mortality in patients with significant cardiovascular disease and may be a stronger secondary than primary risk factor in CAD.

Keywords:
Defined coronary disease, Serum uric acid
1.
Dawber TR, Meadors GF, Moore FE: Epidemiologic approaches to heart disease: The Framingham Study. Am J Public Health 1951;41:279–286.
2.
Longo-Mbenza B, Luila EL, Mbete P, Vita EK: Is hyperuricemia a risk factor of stroke and coronary heart disease among Africans? Int J Cardiol 1999;71:17–22.
3.
Torum M, Yardim S, Simsek B, Burgaz S: Serum uric acid levels in cardiovascular diseases. J Clin Pharm Ther 1998;23:25–29.
4.
Iribarren C, Sharp DS, Curb JD, Yano K: High uric acid: A metabolic marker of coronary heart disease among alcohol abstainers. J Clin Epidemiol 1996;49:673–678.
5.
Brand FN, McGee DL, Kannel WB, Stokes J 3rd, Castelli WP: Hyperuricemia as a risk factor of coronary heart disease: The Framingham Study. Am J Epidemiol 1985;121:11–18.
6.
Reunanen A, Takkunen H, Knekt P, Aromaa A: Uric acid: A risk factor for cardiovascular mortality. Acta Med Scand 1982;668:49–59.
7.
Fessel WJ: High uric acid as an indicator of cardiovascular disease. Independence from obesity. Am J Med 1980;68:401–404.
8.
Wannamethee SG, Shaper AG, Whincup PH: Serum urate and the risk of major coronary heart disease events. Heart 1997;78:147–153.
9.
Freedman DS, Williamson DF, Gunter EW, Byers T: Relation of serum uric acid to mortality and ischemic heart disease. The NHANES I Epidemiologic Follow-up Study. Am J Epidemiol 1995;141:637–644.
10.
Fang J, Alderman MH: Serum uric acid and cardiovascular mortality: The NHANES I Epidemiologic Follow-up Study, 1971–1992. JAMA 2000;283:2404–2410.
11.
Hiyamuta K, Toshima H, Koga Y, Nakayama H, Yamaga A, Shiraishi A, Maruyama H, Hidaka Y, Ueno T, Yoshiga O, et al: Relationship between coronary risk factor and arteriographic feature of coronary atherosclerosis. Jpn Circ J 1990;54:442–447.
12.
Tuttle K, Short R, Johnson R: Sex differences in uric acid and risk factors for coronary artery disease. Am J Cardiol 2001;87:1411–1414.
13.
Leyva F, Wingrove CS, Godsland IF, Stevenson JC: The glycolytic pathway to coronary heart disease: A hypothesis. Metabolism 1998;47:657–662.
14.
Lee J, Sparrow D, Vokonas PS, Landsberg L, Weiss ST: Uric acid and coronary heart disease risk: Evidence for a role of uric acid in the obesity-insulin resistance syndrome. The Normative Aging Study. Am J Epidemiol 1995;142:288–294.
15.
Wilson PW, Cupples LA, Kannel WB: Is hyperglycemia associated with cardiovascular disease? The Framingham Study. Am Heart J 1991;121:586–590.
16.
Facchini F, Chen YD, Hollenbeck CB: Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance, and plasma uric acid concentration. JAMA 1991;266:3008–3011.
17.
Culleton BF, Larson MG, Kannel WB, Levy D: Serum uric acid and risk for cardiovascular disease and death: The Framingham Heart Study. Ann Intern Med 1999;131:7–13.
18.
Taylor GS, Muhlestein JB, Wagner GS, Bair TL, Li P, Anderson JL: Implementation of a computerized cardiovascular information system in a private hospital setting. Am Heart J 1998;136:792–803.
19.
Anonymous: Myocardial infarction and mortality in the coronary artery surgery study (CASS) randomized trial. N Engl J Med 1984;310:750–758.
20.
McClellan T, Jorde LB, Skolnick MH: Genetic distances between the Utah Mormons and related populations. Am J Hum Genet 1984;36:836–857.
21.
Muhlestein JB, Horne BD, Carlquist JF, Madsen TE, Bair TL, Pearson RR, Anderson JL: Cytomegalovirus seropositivity and C-reactive protein have independent and combined predictive value for mortality in patients with angiographically demonstrated coronary artery disease. Circulation 2000;102:1917–1923.
22.
Anderson JL, Muhlestein JB, Horne BD, Carlquist JF, Madsen TE, Bair TL: Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease. Circulation 2000;102:1227–1232.
23.
Horne BD, Muhlestein JB, Carlquist JF, Bair TL, Madsen TE, Hart NI, Anderson JL: Statin therapy, lipid levels, C-reactive protein, and the survival of patients with angiographically severe coronary artery disease. J Am Coll Cardiol 2000;36:1774–1780.
24.
Athyros VG, Elisaf M, Papageorgiou AA, Symeonidis AN, Pehlivanidis AN, Bouloukos VI, Milionis HJ, Mikhailidis DP: Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary disease: A subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Am J Kidney Dis 2004;43:589–599.
25.
Low RK, Stoller ML: Uric acid-related nephrolithiasis. Urol Clin North Am 1997;24:135–148.
© 2005 S. Karger AG, Basel
2005
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.