Older adults overwhelmingly bear the burden of high blood pressure, a condition strongly associated not only with cardiovascular disease, but also with cognitive decline. As life expectancy improves, preservation of cognition in older age has become increasing important to patients, their care givers, and public health. A recent report from the JNC8 committee members suggested liberalizing clinic-based systolic blood pressure targets in persons > 60 years to < 150mmHg compared to < 140mmHg previously, due to lack of data and unproven benefits at lower levels, but this recommendation is being actively debated. Targets for hypertension control and their downstream effects on cognition are the subject of ongoing investigation in SPRINT (Systolic Blood Pressure Intervention Trial), a large, multi-center trial of intensive (<120 systolic) vs. standard (<140 systolic) blood pressure targets in > 9350 hypertensive individuals. Targets in SPRINT (as in the majority of hypertension studies) are based on in-clinic blood pressures. However, `hypertension' is a dynamic phenomenon: 24-hour ambulatory blood pressure (ABPM) patterns, in particular loss of nocturnal dipping (high night/day blood pressure ratio), have been well studied in the cardiovascular literature. My preliminary data supported by my K23-funded observational cohort of healthy older adults suggests that loss of nocturnal dipping and diastolic hypotension on ABPM measurements are associated with worse cognitive function. These associations were not evident using clinic based blood pressure measurements. If confirmed, ABPM measurements could inform the recent debate about the appropriate blood pressure target in older adults. Different in-clinic treatment targets may differentially impact 24-hour blood pressure patterns, and therefore cognitive function. An ongoing already funded SPRINT ancillary study is collecting ABPM readings in a subset of 600 participants in SPRINT with the main goal of evaluating nocturnal BP patterns in the two arms of SPRINT. We are already collaborating with these investigators, however existing funding does not cover the analysis of cognitive function outcomes. This R03 will support analysis to evaluate whether lower diastolic blood pressure and less dipping are associated with cognitive decline in SPRINT, as in our pilot data. We will test whether the effect of intensive blood pressure control on cognitive function is affected by the ABPM pattern achieved with treatment. This low-cost, high-impact study has the opportunity to directly impact hypertension care: if the effect of different treatment targets on cognition can be predicted by the observed ABPM while taking anti-hypertensive treatment, obtaining ABPM in hypertensive older adults would likely become an important part of standard medical practice.

Public Health Relevance

High blood pressure is a common and highly morbid problem, particularly in older adults. Blood pressure is a dynamic phenomenon, with variation from moment to moment and from night to day. We propose to analyze the relationship between 24-hour blood pressure patterns and cognitive function within the context of a large ongoing clinical trial of intensive (in-clinic systolic blood pressure < 120 mm Hg) vs. standard (< 140 mm Hg) treatment. This study, done in the context of a large clinical trial, has the potential to answer important questions about individualized blood pressure targets based on blood pressure patterns rather than on clinic- based blood pressure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Research Grants (R03)
Project #
1R03DK105314-01
Application #
8872964
Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2015-03-01
Project End
2016-12-31
Budget Start
2015-03-01
Budget End
2015-12-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Veterans Medical Research Fdn/San Diego
Department
Type
DUNS #
933863508
City
San Diego
State
CA
Country
United States
Zip Code
92161