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

描述（由申请人提供）：最近的研究报告了收缩压（SBP）访视间变异性（VVV）增加与高风险之间的强相关性 冠心病（CHD）、中风和全因死亡率。这些相关性很强，分级，并且与平均SBP和抗高血压药物使用无关。然而，VVV和心血管疾病（CVD）和死亡率结局的研究有几个局限性，包括非美国人群的入组、少数非洲裔美国人和西班牙裔美国人的入组、相对较小的样本量和少量的血压（BP）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）之间的相关性的数据。在本申请中，我们提出了一项在抗高血压和降脂治疗预防心脏病发作试验（ALLHAT）参与者中进行的二次数据分析，以检查BP的VVV是否与CVD和肾脏疾病事件相关。此外，我们将研究血压VVV增加的临床相关性。1994年2月至1998年1月期间，在美国和加拿大的623个临床研究中心共招募了42，418名ALLHAT研究参与者（35%为非洲裔美国人，19%为西班牙裔美国人，40%为女性）。随访时间为1个月; 3、6、9和12个月;此后每4个月随访一次，直至2002年，延长结局随访至2006年。按照标准化方案，在每次随访访视时测量两次血压，并取平均值进行分析。对于拟定研究，我们将使用6个月至24个月ALLHAT随访访视（6次测量）的BP测量值计算BP的VVV。待分析的主要VVV指标为标准差。已经收集了中位随访7.1年期间的CHD、卒中、心力衰竭、全因死亡率和肾脏疾病结局，并可用于本辅助研究的分析。拟议的研究有可能表明，在迄今为止进行的最大的抗高血压治疗随机对照试验中，血压的VVV与超过平均血压的临床结局相关。ALLHAT是解决这些研究问题的理想环境，因为它提供了一个大型的种族/民族多样化的研究人群，在设定的时间点标准化的BP测量，详细的表型，并收集了长期随访的结果。此外，数据收集是完整的，因此拟议的研究是具有成本效益的。鉴于ALLHAT的大样本量和研究设计，本研究将提供关于BP和结局（包括CHD、卒中、心力衰竭、全因死亡率和肾脏疾病进展以及ESRD）的VVV的明确数据。如果VVV被确认为这些结果的风险因素，它可能会改变BP测量在患者管理中的使用方式（例如，识别高风险患者并指导抗高血压药物的选择）。 公共卫生相关性：患者在就诊期间的血压会有所不同。然而，两次访视之间的血压变异性被认为是一个与未来心血管疾病风险无关的讨厌因素。最近的研究主要针对欧洲的白色人群，发现血压变异性水平较高与中风和冠心病风险增加之间存在密切联系。这项拟议研究的总体目标是确定大量多种族美国成年高血压人群中血压变异性与心血管和肾脏疾病结局之间的相关性。

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). PUBLIC HEALTH RELEVANCE: Blood pressure varies for patients between visits to their doctor. However, blood pressure variability between visits is thought to be a nuisance factor unrelated to risk for future cardiovascular disease risk. Recent studies, primarily in white populations from Europe, have found a strong association between higher levels of blood pressure variability and an increased risk for stroke and coronary heart disease. The overall objective of this proposed study is to determine the association between blood pressure variability and cardiovascular and renal disease outcomes among a large multi-ethnic population of US adults with hypertension.