Hypertension. 2003;41:1183-1190
Published online before print April 21, 2003, doi: 10.1161/01.HYP.0000069700.62727.C5
Published online before print April 21, 2003, doi: 10.1161/01.HYP.0000069700.62727.C5
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2003;41:1183.)
© 2003 American Heart Association, Inc.
Brief Review |
Is There a Pathogenetic Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease?
From the Division of Nephrology (R.J.J., D.-H.K., J.K., S.W., M.M.) and Texas Children’s Hospital (D.F.), Baylor College of Medicine, Houston, Tex; Merck and Company, Inc (S.K.), West Point, Pa; The Heart Institute of Spokane (K.R.T.), Spokane, Wash; Hospital Universitario and Universidad del Zulia (B.R.-I.), Maracaibo, Venezuela; and Instituto de Cardiologia (J.H.-A.), Mexico City, Mexico.
Correspondence to Richard J. Johnson, Baylor College of Medicine, Division of Nephrology, SM-1273, 6550 Fannin St, Houston, TX 77030. E-mail rjohnson{at}bcm.tmc.edu
Hyperuricemia is associated with hypertension, vascular disease, renal disease, and cardiovascular events. In this report, we review the epidemiologic evidence and potential mechanisms for this association. We also summarize experimental studies that demonstrate that uric acid is not inert but may have both beneficial functions (acting as an antioxidant) as well as detrimental actions (to stimulate vascular smooth muscle cell proliferation and induce endothelial dysfunction). A recently developed experimental model of mild hyperuricemia also provides the first provocative evidence that uric acid may have a pathogenic role in the development of hypertension, vascular disease, and renal disease. Thus, it is time to reevaluate the role of uric acid as a risk factor for cardiovascular disease and hypertension and to design human studies to address this controversy.
Key Words: antioxidants • hypertension, essential • cardiovascular diseases • renin-angiotensin system • vascular diseases • renal disease
This article has been cited by other articles:
 |
|
 |
|
  W. Zhang, K. Sun, Y. Yang, H. Zhang, F. B. Hu, and R. Hui Plasma Uric Acid and Hypertension in a Chinese Community: Prospective Study and Metaanalysis Clin. Chem., November 1, 2009; 55(11): 2026 - 2034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Arora, P. Aukrust, T. Ueland, K. Broch, S. Simonsen, E. Gude, A. E. Fiane, O. Geiran, R. Wergeland, A. K. Andreassen, et al. Elevated serum uric acid levels following heart transplantation predict all-cause and cardiac mortality Eur J Heart Fail, October 1, 2009; 11(10): 1005 - 1013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ohtsubo, K. Matsumura, K. Sakagami, K. Fujii, K. Tsuruya, H. Noguchi, I. I. Rovira, T. Finkel, and M. Iida Xanthine Oxidoreductase Depletion Induces Renal Interstitial Fibrosis Through Aberrant Lipid and Purine Accumulation in Renal Tubules Hypertension, October 1, 2009; 54(4): 868 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. Min, I. J. Yun, J. M. Kang, Y. J. Park, S. K. Min, C. Ahn, S. J. Kim, and J. Ha Moderate-to-severe early-onset hyperuricaemia: a prognostic marker of long-term kidney transplant outcome Nephrol. Dial. Transplant., August 1, 2009; 24(8): 2584 - 2590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-C. SEE, C.-F. KUO, F.-H. CHUANG, H.-Y. LI, Y.-M. CHEN, H.-W. CHEN, and K.-H. YU Serum Uric Acid Is Independently Associated with Metabolic Syndrome in Subjects with and without a Low Estimated Glomerular Filtration Rate J Rheumatol, August 1, 2009; 36(8): 1691 - 1698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Bainbridge, J. M. Roberts, F. von Versen-Hoynck, J. Koch, L. Edmunds, and C. A. Hubel Uric acid attenuates trophoblast invasion and integration into endothelial cell monolayers Am J Physiol Cell Physiol, August 1, 2009; 297(2): C440 - C450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Hillis, B. H. Cuthbertson, P. H. Gibson, J. D. McNeilly, G. S. Maclennan, R. R. Jeffrey, K. G. Buchan, H. El-Shafei, G. Gibson, and B. L. Croal Uric acid levels and outcome from coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., July 1, 2009; 138(1): 200 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Luk, G. P. Levin, E. E. Moore, X.-H. Zhou, B. R. Kestenbaum, and H. K. Choi Allopurinol and mortality in hyperuricaemic patients Rheumatology, July 1, 2009; 48(7): 804 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Bainbridge, J.-S. Deng, and J. M. Roberts Increased Xanthine Oxidase in the Skin of Preeclamptic Women Reproductive Sciences, May 1, 2009; 16(5): 468 - 478. [Abstract] [PDF]
|
|
|
|
|
|
T. NEOGI, R. C. ELLISON, S. HUNT, R. TERKELTAUB, D. T. FELSON, and Y. ZHANG Serum Uric Acid Is Associated with Carotid Plaques: The National Heart, Lung, and Blood Institute Family Heart Study J Rheumatol, February 1, 2009; 36(2): 378 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. S. Voruganti, S. D. Nath, S. A. Cole, F. Thameem, J. B. Jowett, R. Bauer, J. W. MacCluer, J. Blangero, A. G. Comuzzie, H. E. Abboud, et al. Genetics of Variation in Serum Uric Acid and Cardiovascular Risk Factors in Mexican Americans J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 632 - 638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Euser, A. Hofman, R. G. J. Westendorp, and M. M. B. Breteler Serum uric acid and cognitive function and dementia Brain, February 1, 2009; 132(2): 377 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Gadegbeku and G. M. Chertow Cum Hoc, Ergo Propter Hoc: Health Disparities Real and Imagined Clin. J. Am. Soc. Nephrol., February 1, 2009; 4(2): 251 - 253. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Pacifico, V. Cantisani, C. Anania, E. Bonaiuto, F. Martino, R. Pascone, and C. Chiesa Serum uric acid and its association with metabolic syndrome and carotid atherosclerosis in obese children Eur. J. Endocrinol., January 1, 2009; 160(1): 45 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Obermayr, C. Temml, G. Gutjahr, M. Knechtelsdorfer, R. Oberbauer, and R. Klauser-Braun Elevated Uric Acid Increases the Risk for Kidney Disease J. Am. Soc. Nephrol., December 1, 2008; 19(12): 2407 - 2413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Choi, M. A. De Vera, and E. Krishnan Gout and the risk of type 2 diabetes among men with a high cardiovascular risk profile Rheumatology, October 1, 2008; 47(10): 1567 - 1570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Luque-Ramirez, F. Alvarez-Blasco, M. G. Uriol Rivera, and H. F. Escobar-Morreale Serum uric acid concentration as non-classic cardiovascular risk factor in women with polycystic ovary syndrome: effect of treatment with ethinyl-estradiol plus cyproterone acetate versus metformin Hum. Reprod., July 1, 2008; 23(7): 1594 - 1601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Annemans, E Spaepen, M Gaskin, M Bonnemaire, V Malier, T Gilbert, and G Nuki Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000-2005 Ann Rheum Dis, July 1, 2008; 67(7): 960 - 966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Meisinger, W. Koenig, J. Baumert, and A. Doring Uric Acid Levels Are Associated With All-Cause and Cardiovascular Disease Mortality Independent of Systemic Inflammation in Men From the General Population: The MONICA/KORA Cohort Study Arterioscler Thromb Vasc Biol, June 1, 2008; 28(6): 1186 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T. Rosolowsky, L. H. Ficociello, N. J. Maselli, M. A. Niewczas, A. L. Binns, B. Roshan, J. H. Warram, and A. S. Krolewski High-Normal Serum Uric Acid Is Associated with Impaired Glomerular Filtration Rate in Nonproteinuric Patients with Type 1 Diabetes Clin. J. Am. Soc. Nephrol., May 1, 2008; 3(3): 706 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Boueiz, M. Damarla, and P. M. Hassoun Xanthine oxidoreductase in respiratory and cardiovascular disorders Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L830 - L840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-L. Chien, M.-F. Chen, H.-C. Hsu, W.-T. Chang, T.-C. Su, Y.-T. Lee, and F. B. Hu Plasma Uric Acid and the Risk of Type 2 Diabetes in a Chinese Community Clin. Chem., February 1, 2008; 54(2): 310 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Kutzing and B. L. Firestein Altered Uric Acid Levels and Disease States J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 1 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Reungjui, C. A. Roncal, W. Mu, T. R. Srinivas, D. Sirivongs, R. J. Johnson, and T. Nakagawa Thiazide Diuretics Exacerbate Fructose-Induced Metabolic Syndrome J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2724 - 2731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Baker, H. R. Schumacher, and E. Krishnan Serum Uric Acid Level and Risk for Peripheral Arterial Disease: Analysis of Data From the Multiple Risk Factor Intervention Trial Angiology, September 1, 2007; 58(4): 450 - 457. [Abstract] [PDF]
|
|
|
|
|
|
V. F. Panoulas, H. J. Milionis, K. M. J. Douglas, P. Nightingale, M. D. Kita, R. Klocke, M. S. Elisaf, and G. D. Kitas Association of serum uric acid with cardiovascular disease in rheumatoid arthritis Rheumatology, September 1, 2007; 46(9): 1466 - 1470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Alderman Podagra, Uric Acid, and Cardiovascular Disease Circulation, August 21, 2007; 116(8): 880 - 883. [Full Text] [PDF]
|
|
|
|
|
|
H. K. Choi and G. Curhan Independent Impact of Gout on Mortality and Risk for Coronary Heart Disease Circulation, August 21, 2007; 116(8): 894 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Y. Sautin, T. Nakagawa, S. Zharikov, and R. J. Johnson Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress Am J Physiol Cell Physiol, August 1, 2007; 293(2): C584 - C596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Gao, L. Qi, N. Qiao, H. K. Choi, G. Curhan, K. L. Tucker, and A. Ascherio Intake of Added Sugar and Sugar-Sweetened Drink and Serum Uric Acid Concentration in US Men and Women Hypertension, August 1, 2007; 50(2): 306 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gullu, D. Erdogan, M. Caliskan, D. Tok, S. Kulaksizoglu, A. Yildirir, and H. Muderrisoglu Elevated serum uric acid levels impair coronary microvascular function in patients with idiopathic dilated cardiomyopathy Eur J Heart Fail, May 1, 2007; 9(5): 466 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Iwanaga, M. Sato, T. Maeda, T. Ogihara, and I. Tamai Concentration-Dependent Mode of Interaction of Angiotensin II Receptor Blockers with Uric Acid Transporter J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 211 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Han, M. J. Lim, Y. J. Lee, J. H. Lee, I. S. Yang, and M. Taub Uric acid inhibits renal proximal tubule cell proliferation via at least two signaling pathways involving PKC, MAPK, cPLA2, and NF-{kappa}B Am J Physiol Renal Physiol, January 1, 2007; 292(1): F373 - F381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. S. Perlstein, O. Gumieniak, G. H. Williams, D. Sparrow, P. S. Vokonas, M. Gaziano, S. T. Weiss, and A. A. Litonjua Uric Acid and the Development of Hypertension: The Normative Aging Study Hypertension, December 1, 2006; 48(6): 1031 - 1036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H J E M Janssens, E H van de Lisdonk, M Janssen, H J M van den Hoogen, and A L M Verbeek Gout, not induced by diuretics? A case-control study from primary care Ann Rheum Dis, August 1, 2006; 65(8): 1080 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Price, Y. Y. Sautin, D. A. Long, L. Zhang, H. Miyazaki, W. Mu, H. Endou, and R. J. Johnson Human Vascular Smooth Muscle Cells Express a Urate Transporter J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1791 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Bos, P. J. Koudstaal, A. Hofman, J. C.M. Witteman, and M. M.B. Breteler Uric Acid Is a Risk Factor for Myocardial Infarction and Stroke: The Rotterdam Study Stroke, June 1, 2006; 37(6): 1503 - 1507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zoccali, R. Maio, F. Mallamaci, G. Sesti, and F. Perticone Uric Acid and Endothelial Dysfunction in Essential Hypertension J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1466 - 1471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Lee, Y.-G. Kim, Y.-H. Choi, W. Huh, D. J. Kim, and H. Y. Oh Serum Uric Acid Is Associated With Microalbuminuria in Prehypertension Hypertension, May 1, 2006; 47(5): 962 - 967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Daghini, A. R. Chade, J. D. Krier, D. Versari, A. Lerman, and L. O. Lerman Acute inhibition of the endogenous xanthine oxidase improves renal hemodynamics in hypercholesterolemic pigs Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R609 - R615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Iwashima, T. Horio, K. Kamide, H. Rakugi, T. Ogihara, and Y. Kawano Uric Acid, Left Ventricular Mass Index, and Risk of Cardiovascular Disease in Essential Hypertension Hypertension, February 1, 2006; 47(2): 195 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-H. Kang, S.-K. Park, I.-K. Lee, and R. J. Johnson Uric Acid-Induced C-Reactive Protein Expression: Implication on Cell Proliferation and Nitric Oxide Production of Human Vascular Cells J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3553 - 3562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Di Serio and P Vicard Graphical chain models for the analysis of complex genetic diseases: an application to hypertension Statistical Modeling, July 1, 2005; 5(2): 119 - 143. [Abstract] [PDF]
|
|
|
|
|
|
R. J. Johnson, M. S. Segal, T. Srinivas, A. Ejaz, W. Mu, C. Roncal, L. G. Sanchez-Lozada, M. Gersch, B. Rodriguez-Iturbe, D.-H. Kang, et al. Essential Hypertension, Progressive Renal Disease, and Uric Acid: A Pathogenetic Link? J. Am. Soc. Nephrol., July 1, 2005; 16(7): 1909 - 1919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Viazzi, D. Parodi, G. Leoncini, A. Parodi, V. Falqui, E. Ratto, S. Vettoretti, G. P. Bezante, M. Del Sette, G. Deferrari, et al. Serum Uric Acid and Target Organ Damage in Primary Hypertension Hypertension, May 1, 2005; 45(5): 991 - 996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Hediger, R. J Johnson, H. Miyazaki, and H. Endou Molecular Physiology of Urate Transport Physiology, April 1, 2005; 20(2): 125 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Domrongkitchaiporn, P. Sritara, C. Kitiyakara, W. Stitchantrakul, V. Krittaphol, P. Lolekha, S. Cheepudomwit, and T. Yipintsoi Risk Factors for Development of Decreased Kidney Function in a Southeast Asian Population: A 12-Year Cohort Study J. Am. Soc. Nephrol., March 1, 2005; 16(3): 791 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sundstrom, L. Sullivan, R. B. D'Agostino, D. Levy, W. B. Kannel, and R. S. Vasan Relations of Serum Uric Acid to Longitudinal Blood Pressure Tracking and Hypertension Incidence Hypertension, January 1, 2005; 45(1): 28 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tinschert, N. Ruf, I. Bernascone, K. Sacherer, G. Lamorte, H.-H. Neumayer, P. Nurnberg, F. C. Luft, and L. Rampoldi Functional consequences of a novel uromodulin mutation in a family with familial juvenile hyperuricaemic nephropathy Nephrol. Dial. Transplant., December 1, 2004; 19(12): 3150 - 3154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ohtsubo, I. I. Rovira, M. F. Starost, C. Liu, and T. Finkel Xanthine Oxidoreductase Is an Endogenous Regulator of Cyclooxygenase-2 Circ. Res., November 26, 2004; 95(11): 1118 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rodriguez-Iturbe, N. D. Vaziri, J. Herrera-Acosta, and R. J. Johnson Oxidative stress, renal infiltration of immune cells, and salt-sensitive hypertension: all for one and one for all Am J Physiol Renal Physiol, April 1, 2004; 286(4): F606 - F616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Johnson and B. A. Rideout Uric Acid and Diet -- Insights into the Epidemic of Cardiovascular Disease N. Engl. J. Med., March 11, 2004; 350(11): 1071 - 1073. [Full Text] [PDF]
|
|
|
|
|
|
K. Masuo, H. Kawaguchi, H. Mikami, T. Ogihara, and M. L. Tuck Serum Uric Acid and Plasma Norepinephrine Concentrations Predict Subsequent Weight Gain and Blood Pressure Elevation Hypertension, October 1, 2003; 42(4): 474 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kanellis and R. J. Johnson Editorial Comment--Elevated Uric Acid and Ischemic Stroke: Accumulating Evidence That It Is Injurious and Not Neuroprotective Stroke, August 1, 2003; 34(8): 1956 - 1957. [Full Text] [PDF]
|
|