Data Analyses for Ancillary WISE Femhrt Hormone Replacement Study
Data Analyses for Ancillary WISE Femhrt Hormone Replacement Study
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.
See Brief Summary above.
Inclusion Criteria

 -  Postmenopausal WISE and nonWISE study participants

 -  Normal/minimally diseased coronary arteries (<50% luminal diameter stenosis in all
 epicardial coronary arteries) within 36 months of ancillary study entry and no
 intercurrent MI, PTCA, CABG

 -  Any one (or multiple) of the following criteria suggestive of myocardial ischemia
 within 36 months of ancillary study entry:

 1. Abnormal P-31 magnetic resonance spectroscopy (a fall in quantitative PCr/ATP
 ratio >15% from control) performed at a WISE or nonWISE site

 2. Positive exercise stress test (> or = 1mm horizontal or downsloping, or > or
 =1.5mm upsloping ST segment depression measured 0.08 msec after the J point),
 performed and/or interpretated by a WISE or WISE ancillary ancillary trial
 investigator

 3. Reversible stress radionuclide perfusion defect > equivocal and not attributable
 to breast/imaging artifact. performed as part of the WISE protocol

 4. Coronary artery flow reserve <2.25 performed. as part of using the WISE protocol

 -  No contraindications to 12 weeks of FemHRT or hormone replacement therapy

 -  Normal mammogram and pelvic exam (including PAP smear for those with an intact uterus)
 within 12 months of study entry

 -  Documented normal liver function testing (SGOT) within 3 months of study entry.

 Exclusion Criteria

 -  Documented myocardial infarction, coronary artery bypass surgery or mechanical
 revascularization

 -  Systolic blood pressure >200 mmHg or diastolic blood pressure >105 mmHg

 -  LDL-cholesterol >190 mg/dl, triglycerides > or = 300 mg/dl

 -  Clinically significant hepatic or renal dysfunction (SGOT more than 1.2 times normal
 at baseline, serum creatinine >2)

 -  Uncontrolled diabetes mellitus (FBS > or = 225 mg/dl) or new onset diabetes until
 stabilized

 -  Clinically significant valvular heart disease, dilated cardiomyopathy, or congestive
 heart failure (NYHA Class IV or severe Class III)

 -  Currently on hormone replacement therapy and unwilling/unable to withdraw treatment
 prior to study, (participants are eligible for study entry 4-8 weeks following hormone
 replacement therapy withdrawal, at the discretion of the WISE ancillary trial
 Principal Investigator)

 -  Previous breast cancer, mammogram suggestive of cancer, or endometrial cancer without
 hysterectomy

 -  Abnormal uterine bleeding or abnormal Pap smear (SIL I, II or III, carcinoma in situ,
 or cancer)

 -  Previous deep venous thrombosis, pulmonary embolism, or other thromboembolic disorder.

 -  Alcoholism or drug abuse

 -  Participation in any other investigational drug or device study

 Women with elevated diastolic (> or = 90 mm Hg) or systolic (> or = 140 mm Hg) blood
 pressure, LDL-cholesterol (> or = 160 mg/dl), fasting blood sugar (> or = 130 mg/dl) and
 women who smoke cigarettes will be told their risk factor levels and referred for
 evaluation and treatment by their private physician.