The present application proposes to extend an ongoing, NHLBI-funded, randomized clinical trial of exercise and diet among individuals with resistant hypertension (Facilities and Web-based Approaches to Lifestyle Change in Resistant Hypertension; R01HL122836) by collecting measures of neurocognitive performance, endothelial function, and cerebrovascular reserve. It is well established that HTN is associated with increased risk of adverse cerebrovascular outcomes, including stroke, and is the most important modifiable risk factor for cognitive decline and dementia. Hypertensive patients exhibit neurocognitive impairments compared with normotensives, as well as microvascular ischemic brain changes. Patients with resistant hypertension (RH), defined as inadequately controlled blood pressure (BP) despite optimal pharmacological treatment, are at even higher risk of adverse clinical events and cognitive impairment compared to patients with controlled HTN. Exercise and diet have been shown to reduce BP and improve neurocognition, providing an intervention opportunity for the mitigation of cognitive impairment. However, the impact of lifestyle change on neurocognition has never been examined among patients with RH. The parent randomized clinical trial (RCT) is designed to examine changes in BP, weight, fitness, and cardiovascular biomarkers among individuals with RH undergoing a comprehensive lifestyle intervention program (C-Life) compared with standardized education and physician advice (SEPA) control condition. The C- Life intervention will consist of supervised aerobic exercise, dietary modification following the Dietary Approaches to Stop Hypertension (DASH) diet, and structured weight loss, whereas participants randomized to SEPA will be provided with information about these healthy lifestyle changes, but will not participate in the intensive, supervised program. The objective of the present proposal is to examine the effects of C-Life on neurocognitive performance, mechanisms of neurocognitive improvement, and maintenance of neurocognitive improvements. In order to accomplish this, we will enhance the parent study by collecting multiple measures of neurocognitive performance (executive function, processing speed, and memory), endothelial function (brachial artery flow mediated dilation), and cerebrovascular reserve (prefrontal cortex cerebral tissue oxygenation index) at baseline, following the 4-month intervention, and again during a one-year follow-up assessment, in tandem with parent trial assessments. The study will aim to evaluate (a) the effectiveness of C- Life on improving neurocognitive function, (b) the impact of C-Life on biomarkers of endothelial function and cerebrovascular reserve, (c) potential mediators of treatment improvements in neurocognitive function, including improvements in fitness, endothelial function, cerebrovascular reserve, BP reduction, and weight loss, and (d) the effects of improved fitness, DASH dietary adherence, reduced body weight, and BP reductions on neurocognitive performance at one-year.

Public Health Relevance

Hypertension is the leading cause of cardiovascular and cerebrovascular disease in the U.S., with a lifetime prevalence of 90% and associated health care expenditures projected to exceed $200 billion annually in the coming decades. Hypertension is the most important modifiable risk factor for cognitive decline, doubling the risk of dementia in later life. Among patients with high blood pressure, individuals with resistant hypertension (RH) are at even greater risk for cognitive decline and dementia. The impact of interventions that improve neurocognition among individuals with RH are therefore needed, as public health expenditures associated with dementia and cognitive impairment are projected to exceed $1.2 trillion annually by mid-century.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
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Kaufmann, Peter G
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Duke University
Schools of Medicine
United States
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Blumenthal, James A; Sherwood, Andrew; Smith, Patrick J et al. (2015) Lifestyle modification for resistant hypertension: The TRIUMPH randomized clinical trial. Am Heart J 170:986-994.e5