ACE Inhibitors Combined With Exercise for Seniors - Pilot Study

The purpose of this study is to compare, when combined with chronic exercise, the effects of perindopril, losartan, and hydrochlorothiazide.

An initial telephone screening will indicate eligibility to participate in the study. The first study visit ("Screening visit") will further determine eligibility to participate. If eligible to fully participate, this study will consist of a structured physical activity program for 24 weeks. In addition, taking daily medication to control your blood pressure and coming to the clinic for several additional assessment visits to monitor your safety and measure study outcomes.

This physical activity program will include moderate-intensity walking, lower-body strengthening, flexibility, and balance training. For the first 12 weeks, of participation there will be three (3) physical activity sessions per week at the physical activity center. These sessions will be led by investigators study staff. These sessions will be used to begin the walking program and to introduce the participant to the strength, stretching, and balance parts of the program in a safe manner. This will allow instructors to better tailor the program to individual needs and abilities. These sessions will involve 40-60 minutes of physical activity instruction. For the final 12 weeks of the intervention, there will be two (2) of these sessions per week.

Participants will also be engage in home-based walking twice per week. This walking can be done at home, community-based physical activity centers (YMCA, senior centers, churches, etc.), or other appropriate facilities as desired. Participants will be asked to report the number of minutes walked each week.

Participants will be randomly assigned to take one of three medications to continue treating blood pressure. These medications are Perindopril, Losartan, and Hydrochlorothiazide. Each medication represents a separate type medication commonly used in practice. These medications are all standard, FDA-approved medications for the treatment of blood pressure. During the time of participating in the study, the use of the normal blood pressure medication will be replaced with the medication assigned during the study. The medications will be inserted into identical capsules by the study pharmacy so that neither participants nor the investigators will know which medication is being used.

Study staff will monitor blood pressure during the study under the supervision of a board-certified cardiologist, and any necessary adjustments to the medication will be indicated by the physician. Participants will also be provided with a blood pressure monitor to use at home during the study and asked to check blood pressure each day and report any abnormal values to study staff. This monitor also automatically records each blood pressure reading. Please bring this monitor to each assessment visit so that study staff can download the stored blood pressure readings.

Eligibility Criteria:
Inclusion Criteria:

* Age 65 years and older
* Hypertension - untreated (Systolic Blood Pressure (SBP) ≥ 140 mm Hg or Diastolic Blood Pressure (DBP) ≥ 90 mm Hg) or treated
* Physical limitations evidenced by either:

Score ≤ 10 on the Short Physical Performance Battery OR Walking speed \< 1.2 m/sec during 400 m usual-paced test

* Sedentary lifestyle, defined as \<150 min/wk of moderate physical activity as assessed by CHAMPS questionnaire
* Willingness to participate in all study procedures

Exclusion Criteria:

* Failure to provide informed consent
* Inability to complete 400 m walk within 15 minutes without sitting or interpersonal assistance, as an indicator of disablement and likely inability to fully engage in the exercise intervention
* Primary indication for ACE inhibitor use, i.e. Congestive Heart Failure, CAD, diabetes
* Known hypersensitivity to ACE inhibitors
* Resistant hypertension, defined as BP \> 140/90, despite the use of three or more anti-hypertensive drugs
* Office or average home SBP \> 180 mm Hg or DBP \> 110 mm Hg (Average home BP in any seven day period during trial)
* Primary renal disease
* Serum creatinine \>2.5 mg/dL in men, or \>2.0 mg/dL in women
* Serum potassium \>5.0 molar equivalent/L
* Urinary protein \> 1 on dipstick
* Abnormal liver enzymes (Aspartate transaminase (AST), Alanine transaminase (ALT), or alkaline phosphatase \> 2.5 times the upper limit of normal)
* Severe cardiac disease, including New York Heart Association Class III or IV congestive heart failure, clinically significant aortic stenosis, history of cardiac arrest, use of a cardiac defibrillator, or uncontrolled angina
* Acute myocardial infarction identified by ECG
* Lives in a nursing home (persons living in assisted or independent housing will not be excluded)
* Significant cognitive impairment, defined as a known diagnosis of dementia or a Mini-Mental State Examination exam score \< 24
* Unable to communicate because of severe hearing loss or speech disorder
* Severe visual impairment, which would preclude completion of the assessments and/or intervention
* Other significant co-morbid disease that would prevent participation in exercise
* Planning to move out of the area during the study time frame
* Simultaneous participation in another intervention trial