Hypertension and adverse cardiovascular outcomes affect individuals with gout and hyperuricemia at disproportionately high rates. Rat models and epidemiological studies have provided significant preliminary evidence for an association between serum urate and hypertension. To further support this hypothesis, urate lowering therapy with allopurinol has been associate with decreased blood pressure in adolescents with hyperuricemia, in one small study. No further studies have confirmed this hypothesis and no translational studies have defined the mechanisms of action through which urate lowering may be contributing to hypertension control in humans. Our major objective is to determine if and through which physiologic mechanisms urate lowering therapy is useful for the treatment of hypertension. Since hypertension is an key comorbid condition in individuals with gout and hyperuricemia, elucidating novel mechanisms for the management of hypertension will be specially beneficial gout patients. We also will focus on the UAB CORT subtheme by studying racial/ethnic differences with a focus in African Americans who disproportionately suffer from this disorder and have differential responses to hypertension therapies.
The Specific Aims of our study aims are to: 1: Determine if in young adults with pre- or stage I hypertension urate-lowering therapy with 300 mg of allopurinol once daily for one month will: a) Induce change in highly sensitive C-reactive protein, b) Induce change in endothelial function, and c) Lower blood pressure 2: Determine if urate-lowering therapy as in Aim 1 induces changes in highly sensitive C-reactive protein, endothelial function and blood pressure that are proportional with the urate lowering achieved. A secondary hypothesis Is that African Americans will have differential responses in the study outcomes compared with other races/ethnicities. This translational study (n= 112 subjects) with physiologic measurements will be a double-blinded, randomized, placebo-controlled, cross-over trial. The target population will be young adults (ages 18-35) with pre-hypertension (SBP 120-139/DBP 80-89) or stage I hypertension (SBP 140-159/DBP 90-99) and with serum urates of >/= 5.0 mg/dL in men and >/= 4.0 mg/dL in women. This novel multi-disciplinary translational study will generate knowledge on the mechanism by which ULT lowers blood pressure and will provide evidence that can be translated into clinical practice for patients with hyperuricemia and gout.

Public Health Relevance

To confirm the usefulness and elucidate the mechanisms for a novel approach for hypertension prevention and control, specially relevant in individuals with hyperuricemia and gout and that can greatly improve cardiovascular outcomes in diverse populations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center (P50)
Project #
5P50AR060772-02
Application #
8525345
Study Section
Special Emphasis Panel (ZAR1-KM)
Project Start
2013-09-01
Project End
2017-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$320,101
Indirect Cost
$109,757
Name
University of Alabama Birmingham
Department
Type
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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Stamp, Lisa K; Merriman, Tony R; Barclay, Murray L et al. (2014) Impaired response or insufficient dosage? Examining the potential causes of "inadequate response" to allopurinol in the treatment of gout. Semin Arthritis Rheum 44:170-4
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