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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Cardiovascular and Sleep Epidemiology Study Section (CASE)
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Einhorn, Paula
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University of Alabama Birmingham
Public Health & Prev Medicine
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Muntner, Paul; Carey, Robert M; Gidding, Samuel et al. (2018) Potential US Population Impact of the 2017 ACC/AHA High Blood Pressure Guideline. Circulation 137:109-118
Muntner, Paul; Carey, Robert M; Gidding, Samuel et al. (2018) Potential U.S. Population Impact of the 2017 ACC/AHA High Blood Pressure Guideline. J Am Coll Cardiol 71:109-118
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