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

降尿酸疗法对炎症、内皮功能和血管生成的影响

基本信息

批准号：
8343827
负责人：
Kenneth G Saag
金额：
$ 38.25万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8343827
关键词：
Acids Adolescent Adult Affect African American Aftercare Age Allopurinol Animals Antihypertensive Agents Blood Pressure C-reactive protein Cardiovascular system Clinical Research Clinical Trials Cross-Over Studies Data Disease Double-Blind Method Endothelial Cells Epidemiologic Studies Epidemiology Ethnic Origin Functional disorder Genetic Crossing Over Gout Human Hypertension Hyperuricemia Hypotension Individual Inflammation Knowledge Measurement Mediating Modeling Nature Nitric Oxide Outcome Outcome Study Participant Patients Pharmaceutical Preparations Physiological Placebo Control Placebos Plasma Population Heterogeneity Probenecid Public Health Race Randomized Rattus Recruitment Activity Renin Research Serum Staging System Target Populations Translating Translational Research Urate Urate Oxidase Vasodilation Woman Xanthine Oxidase cardiovascular risk factor clinical practice design epidemiologic data experience hypertension control hypertension prevention hypertension treatment improved indexing inhibitor/antagonist men novel novel strategies prospective racial/ethnic difference research study response translational study young adult

项目摘要

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.

高血压和不良心血管结局以高度高的速率影响痛风和高尿酸血症的人。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联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，尿酸盐降低治疗与青少年血压的血压降低有关。没有进一步的研究证实了这一假设，并且没有转化研究定义了降低尿素可能导致人类高血压控制的作用机制。我们的主要目的是确定尿酸盐降低疗法是否以及通过哪种生理机制可用于治疗高血压。由于高血压是痛风和高尿酸血症患者的关键合并症，因此阐明高血压治疗的新型机制将是特别有益的痛风患者。我们还将通过研究种族/种族差异的重点，重点放在UAB Cort次级主题上，而非洲裔美国人的重点不成比例地遭受这种疾病，并且对高血压疗法的反应不同。我们研究的具体目的是： 1：确定在患有I期前或阶段高血压尿酸尿酸尿酸尿素治疗的年轻人中，每天使用300 mg别嘌呤醇持续一个月，a）诱导高度敏感的C反应蛋白的变化，b）诱导内皮功能的变化， c）降低血压 2：确定与AIM 1一样降低尿酸的疗法是否诱导高度敏感的C反应蛋白，内皮功能和血压的变化，与尿素降低成正比。次要假设是，与其他种族/种族相比，非洲裔美国人在研究成果中会有不同的反应。这项具有生理测量的翻译研究（n = 112个受试者）将是一项双盲，随机，安慰剂对照，交叉试验。目标人群将是年轻人（18-35岁），具有超高率（SBP 120-139/dbp 80-89）或I期高血压（SBP 140-159/DBP 90-99），以及>/>/尿素的高血压（SBP 140-159/dbp 90-99）男性= 5.0 mg/dl，女性>/= 4.0 mg/dl。这项新型的多学科翻译研究将产生有关降低血压的机制的知识，并将提供可以将高尿酸血症和痛风患者转化为临床实践的证据。