This study will examine the effects of lifestyle intervention on fitness, dietary habits, and body weight in patients with resistant hypertension (RH). Patients will be randomized to either a 4-month adjunctive lifestyle intervention designed to lower BP that will be delivered in a center-based CR program (C-LIFE), or to standardized education and physician advice (SEPA) designed to promote the same healthy behaviors and reflecting the current highest possible standard of care for promoting a healthy lifestyle in RH.

The term resistant hypertension (RH) is defined as clinic blood pressure (BP) that remains above goal (e.g., systolic blood pressure [SBP]>140 mm Hg and/or diastolic blood pressure [DBP]>90 mm Hg), despite adherence to a regimen of 3 or more antihypertensive medications of different classes, one of which is a diuretic.

With the growing prevalence of hypertension (HTN) 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 BP. There is an urgent need for developing RH management strategies to lower BP as well as to reduce the high risk of CVD-related events. Lifestyle modifications, including exercise training and dietary modification, are of proven efficacy in lowering BP in unmedicated patients with HTN and are often recommended as the first step for treating high BP. The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to lower BP in HTN patients who are not treated with drugs. Moreover, when the DASH diet is combined with exercise and caloric restriction, even greater, and quite marked, BP reductions can be achieved. However, the efficacy of these lifestyle modifications in HTN patients who are refractory to medical therapy is unknown. This application aims to build upon evidence supporting the value of lifestyle modifications in unmedicated patients with HTN by proposing a randomized clinical trial (RCT) that will evaluate whether an intensive, medically-supervised lifestyle intervention can successfully lower BP in medicated patients with RH.

Inclusion Criteria:

• Documented resistant hypertension (RH). In the absence of a specific RH diagnosis, individuals being treated for two or more weeks with 3 antihypertensive medications of different classes, including a diuretic if tolerated, with clinic SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg, will be eligible. Individuals being treated with 4 or more antihypertensive medications, including a diuretic if tolerated, with SBP ≥ 120 or DBP ≥ 80 mm Hg will also be eligible.
• Adherent to prescribed medications
• Overweight (BMI ≥ 25 kg/m2)
• Sedentary
• Willing to be randomized to one of the 2 treatment groups and able to fully participate in intervention
• Informed consent

Exclusion Criteria:

• Secondary HTN, non-adherence to anti-HTN medications
• Severe CKD (eGFR <40 ml/min/1.73m2)
• Severe ischemic heart disease (CCS Class 3 or 4 angina or evidence of ischemia at <85% heart rate reserve on treadmill testing)
• Severe heart failure (NYHA association Class 3 or 4), high grade arrhythmias, severe valvular heart disease
• Severe asthma or chronic obstructive lung disease
• Diabetes requiring insulin
• Musculoskeletal or neurologic problems that would preclude participation in aerobic exercise training
• Major psychiatric disorder, a history of drug abuse, alcohol consumption >14 drinks/week
• Life-limiting comorbid medical condition such as cancer
• Prior gastric bypass surgery
• Currently pregnant
• Cognitively impaired