Data Analyses for Ancillary WISE Femhrt Hormone Replacement Study

Not Applicable

Completed

Conditions: Myocardial Ischemia

Interventions: Drug: 1/10 NA/EE
Drug: Placebo

Registration Number: NCT00600106

Lead Sponsor: Cedars-Sinai Medical Center

Brief Summary: The goal of the main trial was to evaluate the effect of low dose hormone replacement therapy with 1 mg norethindrone/10mcg ethinyl estradiol in postmenopausal women with a history of chest discomfort, myocardial ischemia and no obstructive CAD. For the purposes of this study as a core lab coordinating center, the investigators will be performing P31 MRS core lab analyses; hormone core lab analyses; lipid core lab analyses; glucose, insulin and HOMA core lab analyses; exercise stress test/Holter monitor core lab analyses; brachial artery reactivity test core lab analyses; full study data analyses for manuscript preparation and the writing and submission and publication of manuscript.

The main trial duration: December 1999 - May 2003.

The ancillary data analysis project duration: April 2006 - March 2010.

Detailed Description: See Brief Summary above.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 37

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hormone replacement therapy	1/10 NA/EE	Hormone replacement therapy with 1 mg norethindrone/10 mcg thinyl estradiol (1/10 NA/EE)
Placebo	Placebo	1mg placebo

Primary Outcome Measures

Name	Time	Method
Inducible Myocardial Ischemia	12 weeks	Inducible myocardial ischemia measured by P-31 gated magnetic resonance cardiac spectroscopy (MRS) is reported as change (∆) in PCr/ATP ratio, with isometric submaximal handgrip stress. PCr/ATP ratio defined as (stress-\[average of rest and recovery periods\]) / average of rest and recover periods X 100, and expressed as % mean ± SD. For this trial, myocardial ischemia was pre-specified as a fall in quantitative PCR/ATP ratio \>20% from rest, and a lower value is considered indicative of greater ischemia.
Endothelial Dysfunction (FMD)	12 weeks	Endothelial dysfunction refers to altered vasoactive, anticoagulant, and anti-inflammatory properties of endothelium, and dysregulated vascular growth remodeling that results from a loss of nitric oxide (NO) bioactivity in the endothelium. Brachial Artery Reactivity Testing (BART), high-frequency ultrasonographic imaging of the brachial artery, evaluates flow-mediated vasodilation (FMD), an endothelium-dependent function. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function. Flow-mediated vasodilation is typically expressed as the change in post-stimulus diameter as a percentage of the baseline diameter \[diameter after cuff deflation - baseline diameter / baseline diameter) x 100\].

Secondary Outcome Measures

Name	Time	Method
Quality of Life - Menopause Symptoms	12 weeks	Quality of life assessed by menopausal symptoms and psychological questionnaires
Quality of Life - Health Survey	12 weeks	Quality of life assessed by cardiac symptoms and psychological questionnaires (SF 36 scale - Short Form Health Survey) The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Physical Functional Disability - Functional Capacity (Stress Induced ST Segment Depression)	Exit (12 weeks)	Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. In electrocardiography, the ST segment connects the QRS complex and the T wave and has duration of 80 to 120 ms. It should be essentially level with the PR and TP segment. The normal ST segment has a slight upward concavity. Flat, downsloping, or depressed ST segment may indicate coronary ishcemia. Positive treadmill exercise stress test (\>1.0 mm horizontal / downsloping or \>1.5 upsloping ST segment depression measured 0.08 msec after the J point).
Physical Functional Disability - Functional Capacity (METs)	Exit at 12 weeks	Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. A MET is defined as the resting metabolic rate, that is, the amount or oxygen consumet at rest, sitting quietly in a chair, approximately 3.5 ml O2 / kg / min (1.2 kcallmin for a 70-kg person). As such, work at METs requires twice the resting metabolism or 7.0 ml O2/kg/min, and so on.
Physical Functional Disability - Functional Capacity (Metabolism Equivalents)	Exit (12 weeks)	Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain.
Physical Functional Disability - Functional Capacity (Exercise Induced ST Segment Depression)	Baseline	Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. In electrocardiography, the ST segment connects the QRS complex and the T wave and has duration of 80 to 120 ms. It should be essentially level with the PR and TP segment. The normal ST segment has a slight upward concavity. Flat, downsloping, or depressed ST segment may indicate coronary ishcemia. Positive treadmill exercise stress test (\>1.0 mm horizontal / downsloping or \>1.5 upsloping ST segment depression measured 0.08 msec after the J point).