The Effects of Urate Lowering Therapy on Inflammation, Endothelial function, and

痛风和高尿酸血症患者高血压和不良心血管结局的发生率高得不成比例。大鼠模型和流行病学研究为血清尿酸盐与高血压之间的关系提供了重要的初步证据。为了进一步支持这一假设，在一项小型研究中，别嘌呤醇降尿酸治疗与青少年高尿酸血症患者的血压降低有关。没有进一步的研究证实了这一假设，也没有转化研究确定了降低尿酸盐可能有助于人类高血压控制的作用机制。我们的主要目的是确定降尿酸治疗是否以及通过何种生理机制对高血压治疗有效。由于高血压是痛风和高尿酸血症患者的一种重要共病，因此阐明治疗高血压的新机制将对痛风患者特别有益。我们还将通过研究种族/民族差异来关注UAB CORT子主题，重点关注非裔美国人，他们不成比例地患有这种疾病，并对高血压治疗有不同的反应。 我们研究的具体目的是： 一曰：确定在患有I期高血压前期或I期高血压的年轻成人中，每天一次300 mg别嘌呤醇降尿酸治疗1个月是否会：a）诱导高敏C反应蛋白的变化，B）诱导内皮功能的变化，以及c）降低血压 第二章：确定目标1中的降尿酸治疗是否会引起高敏C反应蛋白、内皮功能和血压的变化，这些变化与所达到的降尿酸水平成正比。次要假设是非裔美国人与其他人种/种族相比，在研究结果中的反应存在差异。 本转换研究（n= 112例受试者）采用生理学测量，将是一项双盲、随机、安慰剂对照、交叉试验。目标人群为患有高血压前期（SBP 120-139/DBP 80-89）或I期高血压（SBP 140-159/DBP 90-99）且男性血清尿酸盐>/= 5.0 mg/dL和女性>/= 4.0 mg/dL的年轻人（18-35岁）。这项新的多学科转化研究将产生关于维生素B1降低血压的机制的知识，并将为高尿酸血症和痛风患者提供可转化为临床实践的证据。

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.