Hypertension and Antihypertensive Therapy in Elderly Women
To test our hypotheses, we propose to accomplish the following specific aims:
Specific aim 1: To compare vasomotor sympathetic activity, the magnitude of sympathetic neural responses, vasoconstrictor capability, transduction of sympathetic traffic into vascular resistance, and sympathetic baroreflex function in healthy elderly normotensive and hypertensive men and women (matched for age, race, and body mass index). autonomic function tests will be performed. Blood volume will be measured and insulin resistance will be assessed.
Specific aim 2: To use non-invasive techniques (Doppler ultrasound, tonometry, and cardiac magnetic resonance imaging) to precisely assess pulse wave velocity, aortic artery augmentation pressure and index, dynamic systolic arterial resistance, total arterial compliance, the venoarteriolar response, vasoconstriction in different vascular beds during orthostasis, ventricular mass and geometry, and aortic pulsative dimensions; we will compare ventricular-arterial function in healthy elderly normotensive and hypertensive men and women..
Specific aim 3: To determine if exercise training is an effective strategy in the treatment of hypertension in elderly women by attenuating both ventricular-arterial stiffness and heightened sympathetic activity, hypertensive patients will be assigned randomly either to drug treatment alone [a combination of amlodipine (a calcium channel blocker) and benazepril (an angiotensin-converting enzyme inhibitor), Lotrel plus contact control] or to exercise training (Lotrel and training) for 6 months. The same protocols employed in Specific aims 1 and 2 will be performed before and after treatment. Results will be compared between groups and sexes.
We expect that over a period of 48 months, 180 healthy normotensive controls (90 men, 90 women) and 360 hypertensive patients (180 hypertensive men, 180 hypertensive women) will be consented. However, 120 controls (60 men, 60 women) and 240 patients (120 hypertensive men, 120 hypertensive women) will have screening failures and/or early withdrawals. Thus, 60 controls (30 men, 30 women) and 120 patients (60 hypertensive men, 60 hypertensive women) will complete the entire research project. We expect that mild hypertensive patients will participate in all the studies (aim 1-3), but untreated moderate hypertensive patients (who have not taken antihypertensive drugs for at least one month) will only participate in aim 2 study. it is anticipated that the duration of each subject's participation will be one month for a control subject, and ten months for a mild hypertensive patient, and approximately 3 days for an untreated moderate hypertensive patient.
1) Healthy normotensive controls: Healthy normotensive (blood pressure <120/<80 mmHg) men and women between the ages of 60 and 85 years will be recruited. All subjects will be free of significant underlying medical problems based on detailed medical history and physical exam. None should be endurance-trained athletes.
2) Elderly mild hypertensive patients: Stage I (blood pressure 140-159/90-99 mmHg) hypertensive men and women between the ages of 60 and 85 years with no evidence of target organ disease will be recruited. Patients with previous antihypertensive drug treatment will be free of medication for about 6 weeks before testing.
3) Untreated moderate hypertensive patients: Stage II (blood pressure 160-179/100-109 mmHg) hypertensive men and women between the ages of 60 and 85 years without taking antihypertensive medications for at least 1 month and with no evidence of target organ disease will be recruited. We have consented several untreated moderate hypertensive patients over the past two and half years, but we had to exclude them immediately from the study due to the original inclusion/exclusion criteria. However, there are many elderly moderate hypertensive patients in the US. It is essential to understand how blood pressure is regulated in these patients. In order to reduce the cardiovascular risks in thses patients, we will only perform a non-invasive assessment of ventricular-arterial function and cardiac MRI on them immediately after the screening. After that, they will be requested to resume their previous antihypertensive medications if they still have some at home. If not, we will ask them to see their medical doctor immediately.
All patients and controls will be current non-smokers with a body mass index of <=35 kg/m2, and all will be sedentary (not exercising >30 minutes on >=4 days per week).