Subclinical Renal Artery Atherosclerosis, Kidney Function and Hypertension

描述(由申请人提供)： 高血压(HTN)和慢性肾脏病(CKD)是心血管疾病(CVD)的两个高度流行和强烈的危险因素，它们通过共同的危险因素和病理生理联系在一起。具体地说，肾小球前小动脉的动脉硬化导致相对的肾脏缺血和随后肾素-血管紧张素系统的激活，最终导致血压升高。在这项建议中，我们假设局部(即肾动脉)亚临床动脉粥样硬化与肾功能、血压、高血压和心血管事件显著且独立相关。使用1970年动脉粥样硬化多种族研究(MESA)受试者的动脉钙亚样本，本研究的具体目的是确定：1)肾动脉钙(RAC)是否与肾功能有关，如a)肾小球滤过率、b)胱抑素-C和3)尿白蛋白；2)RAC的基线和预期变化与肾功能的变化和CKD的发生在大约3年的随访中显著相关；3)RAC与四种血压指标相关：a)收缩压，2)舒张压，3)脉压和4)平均动脉压，以及高血压的诊断；4)RAC与高血压和心血管疾病事件显著相关。如果是这样，我们将确定这种联系是否由肾功能差异所调节。我们将通过询问腹部CT扫描的图像来探索这些目标。在加州大学洛杉矶分校的梅萨CT阅读中心，腹部CT图像将根据RAC、肾脏体积和肾脏密度进行评分。血样将检测胱抑素-C、肾素和醛固酮。胱抑素-C的结果将被用作肾功能的衡量标准，并与现有的血肌酐和尿白蛋白数据进行比较。肾素和醛固酮将被用来确定RAC的存在是否与肾素-血管紧张素-醛固酮系统的差异有关。大约700名受试者将在2007年7月之前完成后续扫描，以检验涉及RAC和肾功能预期变化的假设。最后，少数族裔群体在梅萨的代表性过高，这将使人们能够测试与族裔的互动。我们不知道有任何其他以人口为基础的研究足以研究所述的目标。

DESCRIPTION (provided by applicant): Hypertension (HTN) and chronic kidney disease (CKD) are two highly prevalent and strong risk factors for cardiovascular disease (CVD) that are linked via common risk factors and pathophysiology. Specifically, arteriosclerosis of the preglomerular arterioles leads to relative renal ischemia and subsequent activation of the rennin-angiotensin system ultimately leading to increases in blood pressure. In this proposal, we hypothesize that local (i.e. renal artery) subclinical atherosclerosis is significantly and independently associated with kidney function, blood pressure, hypertension and incident CVD events. Using the Aortic Calcium subsample of 1970 subjects from the Multi-Ethnic Study of Atherosclerosis (MESA), the specific aims for this study are to determine if: 1) Renal artery calcium (RAC) is associated with kidney function, as measured by a) glomerular filtration rate, b) cystatin-C and 3) urine albumin; 2) Both baseline and prospective changes in RAC are significantly associated with changes in kidney function and incident CKD over approximately 3 years of follow-up; 3) RAC is associated with four blood pressure (BP) measures: a) systolic BP, 2) diastolic BP 3) pulse pressure and 4) mean arterial pressure, as well as the diagnosis of hypertension; 4) RAC is significantly associated with both incident hypertension and cardiovascular disease events. If so, we will determine if this association is mediated by differences in kidney function. We will explore these aims by interrogating images from computed tomography (CT) scans of the abdomen. The abdominal CT images will be scored for RAC, kidney volume and kidney density at the MESA CT reading center at UCLA. Blood samples will be assayed for cystatin-C, renin and aldosterone. The cystatin-C results will be used as a measure of kidney function and compared with existing data on serum creatinine and urine albumin. Renin and aldosterone will be used to determine if the presence of RAC is associated with differences in the rennin-angiotensin-aldosterone system. Approximately 700 of the subjects will have had follow-up scans completed by July 2007 allowing for testing of hypotheses involving prospective changes in RAC and kidney function. Finally, the overrepresentation of ethnic minority groups in MESA will allow for testing of interactions with ethnicity. We are unaware of any other population-based study adequate to study the stated aims.