AASK COHORT STUDY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 AASK队列研究是AASK临床试验的延伸。(GCRC SPID0301)AASK全规模试验测试了3种不同药物作为一线降压治疗的效果，并测试了两种水平的血压控制，一个通常的目标，一个低的目标。在AASK的1094名参与者中，预计将有650-750人参加队列研究。在队列研究开始时，787名参与者还活着，没有接受透析。其中691人参加了AASK研究的这一阶段。截至2006年3月13日，548人仍然活着，没有接受透析；其中482人至少进行了1个BP测量。 这项纵向队列研究的目的是确定影响因高血压导致的非裔美国人慢性肾脏疾病患者肾功能损失率和模式的因素，并确定AASK试验对慢性肾脏疾病进展的长期影响；自上一次进展报告以来，AASK研究人员提出了五个主要假设。假设1我们计划研究患有慢性肾脏疾病(CKD)的非裔美国人的炎症和心血管疾病之间的联系；研究人员计划将在AASK试验开始时确定的因素与单独在试验阶段以及在试验和队列阶段相结合期间评估的结果联系起来。我们计划确定炎症标志物(C-反应蛋白(CRP)、白介素6(IL-6)、白介素18(IL-18)、血管细胞黏附分子-1(VCAM-1)和肾小球滤过率(EGFR)、血肌酐Scr、蛋白尿度)之间的横断面关系。 V期慢性肾脏病(终末期肾病)和死亡，我们假设在基线水平较高的促炎标志物水平将与未来临床肾脏结果的风险增加相关。假设2我们计划研究N-末端Pro BNP(NT-PRO BNP)与心血管和全因死亡率之间的关系，并假设NT-PRO BNP增加与心血管和全因死亡的风险增加独立相关。假设3我们计划确定夜间血压水平与肾脏疾病进展之间的预期关系，并假设夜间血压升高将与肾脏疾病进展直接相关。我们将研究夜间血压升高与肾脏疾病进展之间的关系，并假设夜间血压升高将直接与肾脏疾病的进展相关；有异常血压曲线的人的进展速度会更快；夜间血压下降的水平将比肾脏疾病的不同类别更能预测肾脏疾病的进展。假设4我们将调查蛋白尿和肾功能随时间加速下降的速度之间的可能联系。我们假设尿蛋白水平的变化与变化前后的EGFR下降速率的变化直接相关；此外，我们假设蛋白尿的变化和EGFR下降速率的变化之间的关联与疾病进展的其他危险因素无关。结果变量EGFR将根据全面试验期间每隔6个月获得的数据计算，并将根据队列研究中每年获得的数据计算。主要的预测变量将在AASK队列受试者中每隔6个月进行一次测量，每年一次。假设5最后，队列研究人员将非裔美国人和归因于HTN非传统危险因素的慢性肾脏病患者作为心血管疾病事件的预测因子与传统危险因素进行比较。研究人员推测，C反应蛋白(CRP)、磷酸盐水平、钙水平、钙磷乘积、尿酸、脂蛋白(A)(LPA)、同型半胱氨酸、左心室重量指数LVNI舒张期功能障碍、动态收缩和舒张期高血压以及贫血与心血管事件的发生有关，与传统的心血管疾病危险因素无关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The AASK Cohort Study is a study that is an extension of the AASK clinical trial. (GCRC SPID 0301) The AASK full scale trial tested the effects of 3 different medications used as first line anti-hypertensive therapy and 2 levels of blood pressure control a usual goal and a low goal. Of the 1,094 participants in AASK, it was anticipated that 650-750 individuals would enroll in the cohort study. At the start of the cohort study, 787 participants were alive and not on dialysis. Of these 691 enrolled in this phase of the AASK study. As of 03/13/06, 548 remain alive and not on dialysis; 482 of the 548 have had at least 1 BP measurement. The purpose of this longitudinal cohort study is to identify factors affecting the rate and pattern of renal function loss in African Americans with Chronic Kidney Disease attributed to hypertension and to determine the long-term effects of the AASK trial on chronic kidney disease progression; Since the last progress report, the AASK investigators have proposed five major hypotheses. Hypothesis 1 We plan to examine the association between inflammation and cardiovascular disease in African Americans with Chronic Kidney Disease (CKD); The investigators plan to relate factors ascertained at the beginning of the AASK trial to outcomes assessed both during the trial phase alone and during the trial and cohort phases combined. We plan to determine the cross sectional relationship between markers of inflammation (C-reactive protein (CRP), interleukin 6 (IL-6), Interleukin 18, (IL-18), VCAM-1, and kidney function determined by estimated glomerular filtration rate (eGFR) serum creatinine Scr, degree of proteinuria) 1. To determine the longitudinal relationship between baseline markers of inflammation and the risk of clinical renal outcomes (reduced glomerular filtration rate (GFR), Stage V CKD (ESRD,) and death we hypothesize that higher levels of pro-inflammatory markers at baseline will be associated with an increased risk of future clinical renal outcomes. Hypothesis 2 We plan to examine the relationship between N-terminal Pro BNP (NT-pro BNP), cardiovascular and all cause mortality and hypothesize that increased NT-pro BNP is independently associated with a greater risk of cardiovascular and all cause mortality. Hypothesis 3 We plan to determine the prospective relationship between level of nocturnal BP and renal disease progression and hypothesize that nocturnal BP elevation will be directly associated with progression of kidney disease. We will examine the relationship between dipping status and kidney disease progression and hypothesize that nocturnal BP elevation will directly be associated with progression of kidney disease; that individuals with abnormal dipping profiles will have a faster rate of progression; and that level of nocturnal dipping status will be a stronger predictor of kidney disease progression than categories of dipping status. Hypothesis 4 We will investigate a possible link between proteinuria and the acceleration in the rate of decline in renal function over time. We hypothesize that changes in the level of proteinuria are directly associated with change in the rate of decline in eGFR between the period prior to and subsequent to the change; additionally we hypothesize that association between the change in proteinuria and change in the rate of decline in eGFR is independent of other risk factors for disease progression Urine protein to creatinine ratios. The outcome variable, eGFR, will be calculated at from data that was obtained at 6 month intervals during the full scale trial and will be calculated from data obtained yearly in the cohort study. The main predictor variable, will be measured in AASK cohort subjects at 6 month intervals and annually. Hypothesis 5 Finally the Cohort investigators will compare in African Americans with CKD attributed to HTN Non-traditional risk factors as predictors of cardiovascular disease events to traditional risk factors. The investigators hypothesize that C-reactive protein (CRP), phosphate level, calcium level, calcium phosphate product, uric acid, lipoprotein(a) (Lpa), homocysteine, UP/Cr left ventricular mass index LVNI diastolic dysfunction, ambulatory systolic and diastolic hypertension, and anemia are associated with development of cardiovascular events independently of traditional CVD risk factors