Serum uric acid: A risk factor and a target for treatment?
Serum uric acid: A risk factor and a target for treatment?
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DOI：
10.1681/asn.2005121331
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发表时间：
2006-04-01
影响因子：
13.6
通讯作者：
Johnson, Richard J.
中科院分区：
文献类型：
--
作者：
Feig, Daniel I.;Mazzali, Marilda;Johnson, Richard J.
19世纪70年代，弗雷德里克·穆罕默德（Frederick Mohamed）首次注意到血清尿酸与血压升高有关。尽管多年来这种联系被定期重新发现，但它通常被视为肾功能下降的替代标志物，导致尿酸增加，高血压和心血管（CV）疾病的风险增加。然而，最近，一些证据表明，血清尿酸升高可能是一个重要的可改变的风险因素。在几项大型纵向临床试验中，血清尿酸升高与未来高血压风险增加相关，也是CV预后不良的独立风险因素。动物模型实验表明，血清尿酸升高导致血压升高，最初是可逆的，但随着时间的推移变得不可逆、盐敏感和尿酸无关。其机制包括尿酸对平滑肌和血管内皮细胞的直接作用。最后，在新发原发性高血压的青少年中，血清尿酸升高的患病率> 90%，初步临床试验证据表明，降低血清尿酸的药物可能会降低这一特定人群的血压。虽然研究仍处于初步阶段，但血清尿酸是降低高血压和CV疾病相关发病率和死亡率的一个可能的新靶点。
Serum uric acid was first noted to be associated with increased BP by Frederick Mohamed in the 1870s. Although the link was rediscovered periodically over the years, it generally was dismissed as a surrogate marker for decreased renal function that led to increased uric acid and increased risk for hypertension and cardiovascular (CV) disease. Recently, however, several lines of evidence suggest that increased serum uric acid may be a significant modifiable risk factor. Increased serum uric acid is associated with increased risk for future hypertension in several large longitudinal clinical trials as well as an independent risk factor for poor CV prognosis. Animal model experiments demonstrate that increased serum uric acid causes increased BP that initially is reversible but becomes irreversible, salt sensitive, and uric acid independent over time. The mechanisms include the direct action of uric acid on smooth muscle and vascular endothelial cells. Finally, in adolescents with new-onset essential hypertension, the prevalence of elevated serum uric acid is > 90%, and preliminary clinical trial evidence suggests that agents that lower serum uric acid may lower BP in this select population. Although the investigations are still preliminary, serum uric acid represents a possible new and intriguing target for the reduction of morbidity and mortality associated with hypertension and CV disease.