Endothelin antagonism and uric acid levels in pulmonary arterial hypertension: Clinical associations
Endothelin antagonism and uric acid levels in pulmonary arterial hypertension: Clinical associations
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DOI：
10.1016/j.healun.2014.01.853
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发表时间：
2014-05-01
影响因子：
8.9
通讯作者：
Webb, David J.
中科院分区：
文献类型：
--
作者：
Dhaun, Neeraj;Vachiery, Jean-Luc;Webb, David J.
背景：肺动脉高压（PAR）患者血清尿酸升高，与患者预后不良相关。高血尿酸是心血管疾病和肾损害的独立危险因素。我们分析了内皮素受体拮抗剂对参加“西他生坦缓解运动受损试验”（STRIDE）-2/2X的PAR患者血清尿酸的影响，以及尿酸对6分钟步行距离（6 MWD）、临床恶化时间（TtCW）和生存率的影响。在为期18周的双盲、安慰剂对照STRIDE-2试验中，246例PAH患者随机接受匹配的安慰剂，西他生坦50或100 mg口服，每日一次，或开放标签波生坦125 mg每日两次。STRIDE-2X是STRIDE-2的一个为期1年的开放标签扩展。结果：两组之间的基线血清尿酸相似。血清尿酸升高是1年死亡率和TtCW的重要危险因素。与安慰剂相比，西他生坦50和100 mg以及波生坦均降低血清尿酸（p < 0.05）。结论：内皮素受体拮抗剂可降低PAR患者的血尿酸，这种降低与生存率的提高和TtCW的延长有关。需要进一步的前瞻性研究来研究血清尿酸在PAH中的致病作用及其预后潜力。(C)2014年国际心肺移植学会。All rights reserved.
BACKGROUND: Elevated serum uric acid is detected in pulmonary arterial hypertension (PAR) 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 PAR 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 PAR 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. (C) 2014 International Society for Heart and Lung Transplantation. All rights reserved.