Visit-to-visit variability of blood pressure and CVD and renal outcomes

描述(由申请人提供)：最近的研究报告称，收缩压(SBP)的就诊-就诊变异性(VVV)增加与更高的风险之间存在很强的相关性 发生冠心病(CHD)、中风和全因死亡的风险。这些相关性是强烈的，分级的，并且独立于平均SBP和降压药物的使用。然而，VVV与心血管疾病(CVD)和死亡率结果的研究有几个局限性，包括非美国人群的登记，纳入少数非裔美国人和拉美裔美国人，相对较小的样本量，以及少量的血压测量。此外，没有关于BP的VVV与肾脏疾病进展和终末期肾脏疾病(ESRD)之间的关联的数据。在这一应用中，我们建议对参加抗高血压和降脂治疗以预防心脏病发作试验(ALLHAT)的参与者进行二次数据分析，以检查BP的VVV是否与心血管事件和肾脏疾病事件有关。此外，我们还将检查BP VVV升高的临床相关性。1994年2月至1998年1月期间，在美国和加拿大的623个临床地点共招募了42,418名ALLHAT研究参与者(35%是非洲裔美国人，19%是西班牙裔，40%是女性)。随访时间分别为1个月、3个月、6个月、9个月和12个月；从2002年起每隔4个月进行一次随访，并延长到2006年的随访结果。根据标准化方案，在每次随访时测量血压两次，并取平均值进行分析。对于拟议的研究，我们将使用从6个月到24个月的ALLHAT随访(6个测量)的血压测量来计算BP的VVV。要分析的主要VVV指标将是标准偏差。我们已经收集了CHD、中风、心力衰竭、全因死亡率和肾脏疾病结果的数据，这些数据的中位数为7.1年，并可在这项辅助研究中进行分析。这项拟议的研究有可能在迄今为止进行的最大规模的抗高血压治疗随机对照试验中表明，血压的VVV与临床结果有关，超过平均血压。ALLHAT是解决这些研究问题的理想环境，因为它提供了大量种族/民族多样化的研究人群，在设定的时间点进行标准化的血压测量，详细的表型，以及长期随访结果的收集。此外，数据收集完整，因此拟议的研究具有成本效益。考虑到ALLHAT的大样本量和研究设计，这项研究将提供关于BP的VVV和结果的明确数据，包括CHD、中风、心力衰竭、全因死亡率、肾脏疾病进展和ESRD。如果VVV被确认为这些结果的风险因素，它可能会改变血压测量在患者管理中的使用方式(例如，识别高危患者和指导抗高血压药物的选择)。

DESCRIPTION (provided by applicant): Recent studies have reported strong associations between increased visit-to-visit variability (VVV) of systolic blood pressure (SBP) and higher risk of incident coronary heart disease (CHD), stroke, and all-cause mortality. These associations were strong, graded, and independent of mean SBP and antihypertensive medication use. However, the studies of VVV and cardiovascular disease (CVD) and mortality outcomes had several limitations including enrollment of non-US populations, inclusion of few African Americans and Hispanics, relatively small sample sizes, and a small number of blood pressure (BP) measurements. Additionally, data are not available on the association of VVV of BP and renal disease progression and end-stage renal disease (ESRD). In this application, we propose a secondary data analysis among participants in the Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) to examine whether VVV of BP is associated with incident CVD and renal disease events. Additionally, we will examine clinical correlates of increased VVV of BP. A total of 42,418 ALLHAT study participants (35% African-American, 19% Hispanic and 40% women) were recruited at 623 clinical sites across the United States and Canada between February 1994 and January 1998. Follow-up visits were at 1 month; 3, 6, 9, and 12 months; and every 4 months thereafter through 2002 with extended outcome follow-up through 2006. BP was measured two times at each follow-up visit following a standardized protocol and will be averaged for analysis. For the proposed study, we will use the BP measurements from the 6 month through 24 month ALLHAT follow-up visits (six measurements) to calculate VVV of BP. The primary VVV metric to be analyzed will be standard deviation. CHD, stroke, heart failure, all- cause mortality and renal disease outcomes over a median of 7.1 years of follow-up have already been collected and are available for analysis in this ancillary study. The proposed study has the potential to show that VVV of BP is associated with clinical outcomes over and above average BP in the largest randomized controlled trial of antihypertensive therapy conducted to date. ALLHAT is an ideal setting to address these research questions as it provides a large racially/ethnically diverse study population, standardized BP measurements at set time points, detailed phenotypes, and the collection of outcomes over a long follow-up period. Furthermore, data collection is complete, so the proposed study is cost-efficient. Given the large sample size and study design of ALLHAT, this study will provide definitive data on VVV of BP and outcomes, including CHD, stroke, heart failure, all-cause mortality and renal disease progression and ESRD. If VVV is confirmed as a risk factor for these outcomes, it may transform how BP measurements are used in patient management (e.g., identifying high risk patients and guiding choice of antihypertensive agents).