Endothelin antagonism and uric acid levels in pulmonary arterial hypertension: Clinical associations

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• 作者：Neeraj Dhaun ; MD^a ; ^{bean.dhaun@ed.ac.uk" class="auth_mail} ; Jean-Luc Vachiery ; MD^b ; Raymond L. Benza ; MD^c ; Robert Naeije ; MD^b ; Lie-Ju Hwang ; PhD^d ; Xuexuan Liu ; MS^e ; Simon Teal ; BSc^f ; David J. Webb ; MD ; FRCP^a
• 关键词：6-minute walk distance ; bosentan ; hyperuricemia ; pulmonary arterial hypertension ; sitaxentan ; uric acid
• 刊名：The Journal of Heart and Lung Transplantation
• 出版年：May, 2014
• 年：2014
• 卷：33
• 期：5
• 页码：521-527
• 全文大小：408 K

文摘

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Background

Elevated serum uric acid is detected in pulmonary arterial hypertension (PAH) and is associated with poor patient outcomes. High serum uric acid is an independent risk factor for cardiovascular disease and renal impairment. We analyzed the effects of endothelin receptor antagonism on serum uric acid in PAH patients participating in the Sitaxentan to Relieve Impaired Exercise (STRIDE)-2/2X trial, and the impact of uric acid on 6-minute walk distance (6MWD), time to clinical worsening (TtCW) and survival.

Methods

In the 18-week, double-blind, placebo-controlled STRIDE-2 trial, 246 PAH patients were randomized and received matched placebo, sitaxentan 50 or 100 mg orally once daily, or open-label bosentan 125 mg twice daily. STRIDE-2X was a 1-year, open-label extension of STRIDE-2.

Results

Baseline serum uric acid was similar between groups. Increased serum uric acid was a significant risk factor for 1-year mortality and TtCW. Compared with placebo, sitaxentan 50 and 100 mg and bosentan all reduced serum uric acid (p < 0.05). Reduced serum uric acid correlated with increased 6MWD (p = 0.0037).

Conclusions

Endothelin receptor antagonism reduces serum uric acid in PAH patients, and this reduction is associated with improved survival and longer TtCW. Further prospective studies are needed to investigate the pathogenic role of serum uric acid in PAH and its prognostic potential.