This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (37)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in JAMA  Topic Collections  • Cardiovascular System, Other  • Pediatrics  • Adolescent Medicine  • Public Health  • Obesity  • Cardiovascular System  • Randomized Controlled Trial  • Drug Therapy  • Adverse Effects  • Drug Therapy, Other  • Hypertension  • Alert me on articles by topic  Social Bookmarking   What's this?

A Randomized Trial

Daniel I. Feig, MD, PhD; Beth Soletsky, RN; Richard J. Johnson, MD

JAMA. 2008;300(8):924-932.

Context  Hyperuricemia is a predictor for the development of hypertension and is commonly present in new-onset essential hypertension. Experimentally increasing uric acid levels using a uricase inhibitor causes systemic hypertension in animal models.

Objective  To determine whether lowering uric acid lowers blood pressure (BP) in hyperuricemic adolescents with newly diagnosed hypertension.

Design, Setting, and Patients  Randomized, double-blind, placebo-controlled, crossover trial (September 2004-March 2007) involving 30 adolescents (aged 11-17 years) who had newly diagnosed, never-treated stage 1 essential hypertension and serum uric acid levels 6 mg/dL. Participants were treated at the Pediatric Hypertension Clinic at Texas Children's Hospital in Houston. Patients were excluded if they had stage 2 hypertension or known renal, cardiovascular, gastrointestinal tract, hepatic, or endocrine disease.

Intervention  Allopurinol, 200 mg twice daily for 4 weeks, and placebo, twice daily for 4 weeks, with a 2-week washout period between treatments. The order of the treatments was randomized.

Main Outcome Measures  Change in casual and ambulatory blood pressure.

Results  For casual BP, the mean change in systolic BP for allopurinol was –6.9 mm Hg (95% confidence interval [CI], –4.5 to –9.3 mm Hg) vs –2.0 mm Hg (95% CI, 0.3 to –4.3 mm Hg; P = .009) for placebo, and the mean change in diastolic BP for allopurinol was –5.1 mm Hg (95% CI, –2.5 to –7.8 mm Hg) vs –2.4 (95% CI, 0.2 to –4.1; P = .05) for placebo. Mean change in mean 24-hour ambulatory systolic BP for allopurinol was –6.3 mm Hg (95% CI, –3.8 to –8.9 mm Hg) vs 0.8 mm Hg (95% CI, 3.4 to –2.9 mm Hg; P = .001) for placebo and mean 24-hour ambulatory diastolic BP for allopurinol was –4.6 mm Hg (–2.4 to –6.8 mm Hg) vs –0.3 mm Hg (95% CI, 2.3 to –2.1 mm Hg; P = .004) for placebo. Twenty of the 30 participants achieved normal BP by casual and ambulatory criteria while taking allopurinol vs 1 participant while taking placebo (P < .001).

Conclusions  In this short-term, crossover study of adolescents with newly diagnosed hypertension, treatment with allopurinol resulted in reduction of BP. The results represent a new potential therapeutic approach, although not a fully developed therapeutic strategy due to potential adverse effects. These preliminary findings require confirmation in larger clinical trials.

Trial Registration  clinicaltrials.gov Identifier: NCT00288184

Author Affiliations: Department of Pediatrics, Renal Section, Baylor College of Medicine, Houston, Texas (Dr Feig and Ms Soletsky); and Division of Nephrology, Hypertension and Transplantation, Department of Medicine, University of Florida School of Medicine, Gainesville (Dr Johnson).

CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

RELATED LETTERS

Allopurinol and the Role of Uric Acid in Hypertension
Allen D. Brinker
JAMA. 2009;301(3):270.
EXTRACT | FULL TEXT  

Allopurinol and the Role of Uric Acid in Hypertension—Reply
Daniel I. Feig and Richard J. Johnson
JAMA. 2009;301(3):270-271.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

World Congress on the Insulin Resistance Syndrome, 2009: The kidney, the liver, and insulin resistance
Bloomgarden
Diabetes Care 2010;33:e116-e120.
FULL TEXT  

Increased Fructose Associates with Elevated Blood Pressure
Jalal et al.
J. Am. Soc. Nephrol. 2010;21:1543-1549.
ABSTRACT | FULL TEXT  

Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo
Hershfield et al.
Proc. Natl. Acad. Sci. USA 2010;107:14351-14356.
ABSTRACT | FULL TEXT  

Gout, Allopurinol Use, and Heart Failure Outcomes
Thanassoulis et al.
Arch Intern Med 2010;170:1358-1364.
ABSTRACT | FULL TEXT  

Inflammation, oxidative stress and lipids: the risk triad for atherosclerosis in gout
Krishnan
Rheumatology (Oxford) 2010;49:1229-1238.
ABSTRACT | FULL TEXT  

Role of uric acid in the link between arterial stiffness and cardiac hypertrophy: a cross-sectional study
Kuo et al.
Rheumatology (Oxford) 2010;49:1189-1196.
ABSTRACT | FULL TEXT  

Hyperuricemia and Incident Heart Failure
Krishnan
Circ Heart Fail 2009;2:556-562.
ABSTRACT | FULL TEXT  

Recent insights into the pathogenesis of hyperuricaemia and gout
Riches et al.
Hum Mol Genet 2009;18:R177-R184.
ABSTRACT | FULL TEXT  

A novel role for uric acid in acute kidney injury associated with tumour lysis syndrome
Shimada et al.
Nephrol Dial Transplant 2009;24:2960-2964.
FULL TEXT  

Dietary Sugars Intake and Cardiovascular Health: A Scientific Statement From the American Heart Association
Johnson et al.
Circulation 2009;120:1011-1020.
ABSTRACT | FULL TEXT  

Allopurinol and the Role of Uric Acid in Hypertension
Brinker
JAMA 2009;301:270-270.
FULL TEXT  

What's new in hypertension 2008?
Mann
Nephrol Dial Transplant 2009;24:38-42.
FULL TEXT  

Allopurinol Lowers Blood Pressure in Mild Hypertension
JWatch Pediatrics 2008;2008:1-1.
FULL TEXT