Medical Student Research Fellowship for Summer 2010

Mentor: Qi Fu, M.D., Ph.D.
Department: Internal Medicine, Cardiology Division
Room number: Institute for Exercise and Environmental Medicine (IEEM)
Mail Code: None
Phone number: 214-345-8125
E-mail: QiFu@TexasHealth.org
Project title: Hypertension and Antihypertensive Therapy in Elderly Women

Human subjects IRB approved project number (where applicable): 022008-081

Animal subjects IRB approved project number (where applicable): NA

Project Type: Patient-based research

Brief Description of Project: Hypertension is a major public health problem worldwide affecting over 50 million Americans. It is a major risk factor for target organ damage resulting in coronary artery disease, heart failure, stroke, and kidney disease. Large epidemiological surveys have shown that more elderly women than men have hypertension. Whether this specific effect of sex is grounded in equally specific pathophysiology which could "personalize" the selection of antihypertensive therapy and improve the response to treatment is unknown.

The primary goal of this research proposal is to determine the mechanisms underlying sex differences in hypertension in sedentary seniors (i.e., 65 years old), and to determine whether exercise training in combination with antihypertensive drug treatment is effective in elderly women. Using the innovative techniques of microneurography, Doppler ultrasound, and tonometry, Specific Aim 1 will test the hypothesis that sympathetic neural activity is augmented in elderly hypertensive women. Autonomic function tests will be performed; sympathetic neural responses, vasoconstrictor capability, transduction of sympathetic traffic into vascular resistance, and baroreflex function will be compared in elderly normotensive and hypertensive men and women. Specific Aim 2 will test the hypothesis that ventricular-arterial stiffening is more prominent in elderly hypertensive women than men. Pulse wave velocity, dynamic systolic arterial elastance, aortic artery augmentation pressure and index, total arterial compliance, cardiac size, and aortic pulsative dimensions will be compared between normotensive and hypertensive men and women. Specific Aim 3 will test the hypothesis that a long-term exercise training program in combination with antihypertensive drug treatment is more effective than pharmacologic therapy alone in hypertensive seniors, and the responses to exercise training differ between sexes. Patients enrolled in Specific Aim 1 and 2 studies will be assigned randomly either to drug treatment alone [a combination of losartan (AT1 receptor antagonist) and hydrochlorothiazide (diuretic), Hyzaar plus contact control] or to exercise training (Hyzaar and exercise training) for 6 months, the same protocols employed in Specific Aim 1 and 2 will be repeated after treatment, and results will be compared among groups and between sexes.

Upon completion of this project, we will have obtained novel and clinically important information regarding the nature of hypertension associated with aging and sex, the selection of antihypertensive therapy, and the responses to treatment in elderly hypertensive men and women. We will identify the mechanisms underlying sex differences in hypertension and antihypertensive therapy in seniors, which may lead to more effective therapies for this particularly patient population.

Previous Research Activities or Publications with Medical Students:

Jaeon Abraham July 08 - May 09 Medical Student Gender & Orthostatic Tolerance: Mechanisms and Therapy UT Southwestern Medical Center NIH
Jay Joseph July - Sep 07 Medical Student Gender & Orthostatic Tolerance: Mechanisms and Therapy UT Southwestern Medical Center NIH