Hypertension (HTN) is considered to be the single most important risk factor for adverse cardiovascular events, including stroke, myocardial infarction and death. It has been estimated that 70% of the 68 million American adults with HTN receive pharmacological treatment, but only 46% have their blood pressure (BP) adequately controlled. Patients with BP that remains above goal (systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg) despite the concurrent use of 3 or more classes of antihypertensive medications, including a diuretic, are considered to have resistant hypertension (RH). With the growing prevalence of HTN in this country, RH is a major public health concern, affecting more than 7.5 million Americans. Patients with RH are at high risk for CVD-related events, and there is a need to develop effective management strategies to help lower BP and reduce risk in these individuals. Surprisingly, there have been no randomized clinical trials (RCTs) evaluating whether an adjunctive lifestyle intervention that combines exercise, weight loss, and optimal nutrition featuring the DASH diet may help control BP and reduce CVD risk in patients with RH. This proposed RCT is designed to evaluate whether RH patients can achieve clinically significant BP lowering and improve other biomarkers of CVD risk through a lifestyle intervention delivered in a center-based cardiac rehabilitation facility (C-LIF) compared to a standardized education and physician advice control condition (SEPA). One hundred fifty men and women with RH will be randomized in a 2:1 design to C-LIFE or SEPA. We hypothesize that C-LIFE participants will (1) exhibit greater improvements in aerobic fitness, greater adherence to the DASH diet, and greater weight loss after 4 months compared to SEPA controls; (2) exhibit lower clinic BP and ambulatory BP after 4 months compared to SEPA controls; (3) exhibit greater regression of LV hypertrophy and greater improvements in CVD risk biomarkers including arterial stiffness, baroreceptor reflex sensitivity, insulin resistance, and inflammatory markers after 4 months compared to SEPA controls; (4) exhibit lower clinic BP and ABP, and improved CVD biomarkers at 1 year follow-up compared to SEPA controls. We also hypothesize that greater aerobic fitness, better adherence to the DASH diet, and greater weight loss will be associated with greater reductions in clinic BP at 4 months and at 1 year follow-up. I successful, the lifestyle intervention described in this application could be adopted by cardiac rehabilitation programs nationwide, and provide a viable non-pharmacologic treatment for managing patients with RH.

Public Health Relevance

Resistant hypertension (RH) is defined as blood pressure that remains above goal, despite adherence to a regimen of 3 or more classes of optimally-dosed antihypertensive medications, one of which is a diuretic. With the growing prevalence of hypertension in this country, RH is a major public health concern, affecting more than 7.5 million Americans. Patients with RH are 50% more likely to experience a CVD event, including stroke, kidney failure, myocardial infarction, and death, compared to patients with controlled blood pressure, underscoring the urgent need for developing RH management strategies to lower BP as well as to reduce the high risk of CVD-related events. The data generated from this clinical trial will have important and readily translatable treatment implications by determining whether a lifestyle intervention can lower blood pressure and reduce cardiovascular risk in patients with hypertension who have not responded adequately to antihypertensive medications.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL122836-03
Application #
9189649
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Einhorn, Paula T
Project Start
2014-12-01
Project End
2019-11-30
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Duke University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Smith, P J; Blumenthal, J A (2016) Dietary Factors and Cognitive Decline. J Prev Alzheimers Dis 3:53-64
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