Reduction of Triglycerides in Women on Hormone Replacement Therapy

Study Overview
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Brief Summary
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The purpose of this study is to test the effect of lifestyle intervention on subclinical cardiovascular disease measures in women taking hormone replacement therapy (HRT).

Detailed Description
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BACKGROUND: Cardiovascular disease is a common cause of morbidity and mortality in older women. Better methods of prevention via health promotion are needed. Estrogen HRT may beneficially affect women's cardiovascular health, based on evidence from observational studies, but recent trial evidence suggests HRT may actually lead to increased risk of cardiovascular disease in new users. Understanding this untoward effect of HRT and how to prevent it is a significant aim. DESIGN NARRATIVE: This randomized trial of 500 women on HRT for at least two years, aged 52-60 years, and three or more years postmenopausal will test whether reduction in waist circumference, triglycerides, dense low density lipoprotein cholesterol (LDLc), number of LDL particles, C-reactive protein, and plasminogen activator inhibitor-I (PAI-I) by aggressive diet and exercise, versus a health education control, and will decrease progression or result in regression of measures of subclinical vascular disease. The intervention is designed to reduce total fat intake to 17 percent of calories, 1300 kilo calories, and increase moderate activity to 150-240 minutes per week to obtain a 10 percent reduction in weight. The primary endpoint will be a 20 percent or at least a 20 mg decrease in triglyceride levels, a 5 cm decrease in waist circumference, and a 10 percent decrease in LDLc. This will result in changes in subclinical measurements, including carotid ultrasound, electron beam computer tomography of the coronary artery and aorta, pulse wave velocity, endothelial function, and tonometry of the radial artery. Nuclear magnetic resonance spectroscopy of lipoproteins, inflammatory markers, and estrogen metabolites will also be evaluated.

Official Title
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Reduction of Triglycerides in Women on HRT

Conditions
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Cardiovascular Diseases, Atherosclerosis, Postmenopause, Heart Diseases

Intervention / Treatment
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* Behavioral: Diet, fat-restricted
* Behavioral: Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: On HRT for at least two years Women 52 to 60 years of age Three or more years postmenopausal Waist circumference greater than 80 cm LDLc between 100 and 160 mg/dl Body mass index 25-39.9 kg/m2 Blood Pressure less than 160/95 mm Hg Beck Depression Inventory Score less than 20 Exclusion Criteria: Current use of cholesterol-lowering medication Diagnosis of diabetes On diabetes medication

Ages Eligible for Study
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Minimum Age: 52 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will reduce total fat intake to 17 percent of calories, 1300 kilo calories, and increase moderate activity to 150-240 minutes per week to obtain a 10 percent reduction in weight. | Behavioral: Diet, fat-restricted<br>* Reduction in total, saturated, trans fat, cholesterol, calories. Increase in fiber. Promotion of nutrient-dense, high-volume, low calorie foods.<br>Behavioral: Exercise<br>* Rigorous, stepped care approach to reach 150 min/week of physical activity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measures of subclinical disease |  | 5 years | 
| Change in coronary calcium (EBCT) |  | 5 years | 
| Change in carotid intima media wall thickness |  | 5 years | 
| Change in vascular stiffness (PWV) |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in waist circumference and weight |  | 5 years | 
| Change in LDL particles, triglycerides and small, medium and large LDL particles |  | 5 years | 
| Change in HDL particles |  | 5 years | 
| Change in insulin and glucose |  | 5 years | 
| Change in systolic blood pressure, diastolic blood pressure |  | 5 years |