Masked Hypertension in Chronic Kidney Disease

描述(由申请人提供)： 背景：越来越多的人认识到，与临床上的血压记录相比，临床外的血压记录更能预测心肾功能不良的预后。当在临床和室外都记录血压时，可以根据血压记录的位置对高血压进行分类。这些类别包括白大衣高血压、持续正常血压(NTN)、持续高血压(HTN)和隐性高血压(MHTN)。MHTN在临床上被定义为血压正常，但在临床上被定义为血压升高。我们的荟萃分析显示，40%被认为血压正常的CKD患者实际上患有MHTN。迄今为止研究的最大的CKD队列包括对209名患者的横断面分析(通过这段时期的VAMR资助)，这些患者之所以被选中，是因为他们在临床上血压正常(&lt；140/90 mm Hg)。我们发现MHTN的患病率约为40%。我们首次证明了MHTN的诊断是可重复性的。即使在没有慢性肾脏病的患者中，这在过去也没有报道过。此外，在我们的队列中，MHTN与更大的左心室重量指数、动脉僵硬、更多的蛋白尿和夜间钠尿相关。长期目标：这项研究在患有慢性肾脏病的退伍军人中的总体目标是调查靶器官损害、预后和“隐性高血压”的机制，“隐性高血压”的定义是平均醒着的动态压力大于或等于125/75毫米汞，临床血压低于130/80毫米汞。假设：我们假设NTN、MHTN和HTN是一个连续体。我们假设，NTN、MHTN和HTN之间将存在分级关系，即高血压类别越差，将：1)高血压恶化，从而更严重的终末器官损害；2)将经历更多的全因死亡率和心血管和肾脏疾病；3)与更大的靶器官损害和死亡率相关，其程度将取决于MHTN的定义；以及4)经历更严重的睡眠障碍，白天体力活动减少，体脂增加，以及更严重的运动导致的血压升高。此外，膳食钠摄入量将调节随后的动态血压升高和其他不良后果。目的：这项拟议的研究将使我们能够确定(1)NTN、MHTN和HTN之间高血压恶化的发生率和靶器官损害的发生，(2)比较高血压类别中心肾事件(住院心力衰竭、MI、中风、ESRD、肾移植、死亡)的发生率(3)比较MHTN的两种定义(上述针对CKD的定义和MHTN的传统定义)的预后价值，以及(4)研究MHTN与睡眠障碍、白天活动减少、肥胖增加以及随着钠摄入量增加而动态血压增加的机制关系。方法：本研究对450例慢性肾脏病合并NTN、MHTN和HTN患者进行研究。参与者将在一个月内测量三次诊所血压，一次动态血压，两次家庭血压。靶器官损害将通过超声心动图的左心室重量和脉搏波速度以及24小时尿蛋白尿来评估。考试将每两年重复一次。将使用便携式多通道夜间睡眠监测来测量睡眠。身体成分将通过空气置换体积描记仪(BOD Pod)的金标准测量来测量。活动将通过7天手腕加速度计进行测量。体力活动的升压效应将在自行车测功器上测量到。我们将跟踪观察ESRD和心血管事件。新颖性：这项建议将为CKD患者隐匿性高血压的预后意义和机制提供新的见解。与VA的相关性：这项研究增加了我们对临床和非临床血压监测之间的差异的理解，它将有助于解释为什么后者是更好的预后指标。对隐匿性高血压患者的靶器官损害、ESRD和心血管事件的评估可能会揭示其恶性特征，并提高我们更有效地治疗这种疾病的能力。

DESCRIPTION (provided by applicant): Background: It is being increasingly recognized that compared to BP recordings in the clinic, BP recordings outside the clinic are stronger predictors of poor cardiorenal outcomes. When BP is recorded both in the clinic and outside, hypertension can be categorized depending on the location of BP recording. These categories include white coat hypertension, sustained normotension (NTN), sustained hypertension (HTN), and masked hypertension (MHTN). MHTN is defined as normal BP in the clinic but elevated BP outside the clinic. Our meta-analysis revealed that 40% of CKD patients thought to be normotensive in fact had MHTN. The largest CKD cohort studied to date included a cross-sectional analysis of 209 patients (enabled through this period of VAMR funding) who were selected because they had normal BP (<140/90 mmHg) in the clinic. We found that the prevalence of MHTN was ~40%. For the first time we demonstrated that the diagnosis of MHTN was reproducible. This has not been reported in the past even among patients without CKD. Moreover, MHTN in our cohort was associated with greater left ventricular mass index, increased arterial stiffness, greater albuminuria, and nocturnal natriuresis. Long-term goal: The overall goal of this study in Veterans with CKD is to investigate target organ damage, prognosis, and mechanisms of "masked hypertension ", defined by an average awake ambulatory pressure of 125/75 mm Hg or more and clinic BP below 130/80 mm Hg. Hypothesis: We hypothesize that NTN, MHTN and HTN is a continuum. We hypothesize that a graded relationship among NTN, MHTN and HTN will exist such that with a worse hypertension category will: 1) have greater worsening of hypertension and therefore greater end-organ damage; 2) will experience greater all-cause mortality and cardiovascular and renal morbidity; 3) have associations with greater target organ damage and mortality the magnitude of which will depend on how MHTN is defined; and 4) experience greater sleep disturbances, reduced day-time physical activity, increased body fat, and greater exercise-induced increased BP. Also, dietary Na intake will modulate subsequent increase in ambulatory BP and other adverse outcomes. Goals: This proposed study will enable us to determine (1) the incidence of worsening of hypertension and the occurrence of target organ damage among NTN, MHTN, and HTN, (2) Compare the incidence of cardiorenal events (hospitalized heart failure, MI, stroke, ESRD, kidney transplantation, death) among the hypertension categories (3) Compare the prognostic value of two definitions of MHTN (a CKD-specific definition, noted above and the conventional definition of MHTN) and (4) examine the mechanistic relationship of MHTN with sleep disturbances, reduced day-time activity, increasing adiposity and increments in ambulatory BP with greater sodium intake. Methods: This project will study 450 subjects with CKD with NTN, MHTN, and HTN. Participants will have their clinic BP measured on three occasions, ambulatory BP once, and home BP twice over a one month period. Target organ damage will be assessed using LV mass and pulse wave velocity by echocardiogram and 24 hour urine for albuminuria. Examinations will be repeated biannually. Sleep will be measured using portable multichannel overnight sleep monitoring. Body composition will be measured by the gold-standard measurement of air-displacement plethysmography (Bod Pod). Activity will be measured by 7-day wrist accelerometer. Greater pressor effect with physical activity will be measured on a bicycle ergometer. We will follow for ESRD and cardiovascular events. Novelty: This proposal will provide new insights on the prognostic implications and mechanisms of masked hypertension in patients with CKD. Relevance to VA: To the extent that this study increases our understanding of the differences between clinic and out of clinic BP monitoring, it will help to explain why the latter is a better indicator of prognosis. The evaluation of target organ damage, ESRD, and cardiovascular events among those with masked hypertension may unmask its malignant characteristics and improve our ability to treat this condition more effectively.