title: Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.
abstract: Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive, overweight, or obese individuals with higher serum uric acid (body mass index ≥25 kg/m2and serum uric acid ≥5.0 mg/dL), we assigned subjects to probenecid (500-1000 mg/d), allopurinol (300-600 mg/d), or matching placebo. The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49, and 53 participants had been allocated to receive probenecid, allopurinol, and placebo, respectively. Mean serum uric acid levels significantly decreased in the probenecid (from 6.1 to 3.5 mg/dL) and allopurinol groups (from 6.1 to 2.9 mg/dL) but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelium-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension.
authors.affiliation: From the Renal Division (L.B., C.M., A.W., G.C.C., J.P.F.) and Division of Endocrinology, Diabetes and Hypertension (N.D.F.), Brigham and Women's Hospital, Boston, MA; and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.C.C., J.P.F.). lborgi@partners.org.
authors.forename: Lea
authors.initials: L
authors.lastname: Borgi
authors.affiliation: From the Renal Division (L.B., C.M., A.W., G.C.C., J.P.F.) and Division of Endocrinology, Diabetes and Hypertension (N.D.F.), Brigham and Women's Hospital, Boston, MA; and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.C.C., J.P.F.).
authors.forename: Ciaran
authors.initials: C
authors.lastname: McMullan
authors.affiliation: From the Renal Division (L.B., C.M., A.W., G.C.C., J.P.F.) and Division of Endocrinology, Diabetes and Hypertension (N.D.F.), Brigham and Women's Hospital, Boston, MA; and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.C.C., J.P.F.).
authors.forename: Ann
authors.initials: A
authors.lastname: Wohlhueter
authors.affiliation: From the Renal Division (L.B., C.M., A.W., G.C.C., J.P.F.) and Division of Endocrinology, Diabetes and Hypertension (N.D.F.), Brigham and Women's Hospital, Boston, MA; and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.C.C., J.P.F.).
authors.forename: Gary C
authors.initials: GC
authors.lastname: Curhan
authors.affiliation: From the Renal Division (L.B., C.M., A.W., G.C.C., J.P.F.) and Division of Endocrinology, Diabetes and Hypertension (N.D.F.), Brigham and Women's Hospital, Boston, MA; and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.C.C., J.P.F.).
authors.forename: Naomi D
authors.initials: ND
authors.lastname: Fisher
authors.affiliation: From the Renal Division (L.B., C.M., A.W., G.C.C., J.P.F.) and Division of Endocrinology, Diabetes and Hypertension (N.D.F.), Brigham and Women's Hospital, Boston, MA; and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.C.C., J.P.F.).
authors.forename: John P
authors.initials: JP
authors.lastname: Forman
mesh_terms: D000328:Adult; D000493:Allopurinol / Q000008:administration & dosage*; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006074:Gout Suppressants / Q000008:administration & dosage; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D050177:Overweight / Q000150:complications; D011339:Probenecid / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D018608:Ultrasonography, Doppler; D014527:Uric Acid / Q000097:blood*; D014528:Uricosuric Agents / Q000008:administration & dosage; D014664:Vasodilation / Q000502:physiology*
chemical_list: D006074:Gout Suppressants; D014528:Uricosuric Agents; D014527:Uric Acid; D000493:Allopurinol; D011339:Probenecid
keywords: allopurinol; blood pressure; probenecid; uric acid