Dataset Information

A randomized controlled trial of low-dose hormone therapy on myocardial ischemia in postmenopausal women with no obstructive coronary artery disease: results from the National Institutes of Health/National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

ABSTRACT:

Background

Compared with men, women have more evidence of myocardial ischemia with no obstructive coronary artery disease. Although low endogenous estrogen levels are associated with endothelial dysfunction, the role of low-dose hormone therapy has not been fully evaluated. We postulate that a 12-week duration of low-dose hormone replacement therapy is associated with myocardial ischemia and endothelial dysfunction.

Methods and results

Using a multicenter, randomized, placebo-controlled design, subjects were randomized to receive either 1 mg norethindrone/10 microg ethinyl estradiol or placebo for 12 weeks. Chest pain and menopausal symptoms, cardiac magnetic resonance spectroscopy, brachial artery reactivity, exercise stress testing, and psychosocial questionnaires were evaluated at baseline and exit. Recruitment was closed prematurely because of failure to recruit after publication of the Women's Health Initiative hormone trial. Of the 35 women who completed the study, there was less frequent chest pain in the treatment group compared with the placebo group (P = .02) at exit. Women taking 1 mg norethindrone/10 microg ethinyl estradiol also had significantly fewer hot flashes/night sweats (P = .003), less avoidance of intimacy (P = .05), and borderline differences in sexual desire and vaginal dryness (P = .06). There were no differences in magnetic resonance spectroscopy, brachial artery reactivity, compliance, or reported adverse events between the groups.

Conclusions

These data suggest that low-dose hormone therapy improved chest pain symptoms, menopausal symptoms, and quality of life, but did not improve ischemia or endothelial dysfunction. Given that it was not possible to enroll the prespecified sample size, these results should not be considered definitive.

SUBMITTER: Merz CN

PROVIDER: S-EPMC2918903 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Publications

A randomized controlled trial of low-dose hormone therapy on myocardial ischemia in postmenopausal women with no obstructive coronary artery disease: results from the National Institutes of Health/National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

Merz C Noel Bairey CN Olson Marian B MB McClure Candace C Yang Yu-Ching YC Symons James J Sopko George G Kelsey Sheryl F SF Handberg Eileen E Johnson B Delia BD Cooper-DeHoff Rhonda M RM Sharaf Barry B Rogers William J WJ Pepine Carl J CJ

American heart journal 20100601 6

<h4>Background</h4>Compared with men, women have more evidence of myocardial ischemia with no obstructive coronary artery disease. Although low endogenous estrogen levels are associated with endothelial dysfunction, the role of low-dose hormone therapy has not been fully evaluated. We postulate that a 12-week duration of low-dose hormone replacement therapy is associated with myocardial ischemia and endothelial dysfunction.<h4>Methods and results</h4>Using a multicenter, randomized, placebo-cont ...[more]

PMID: 20569710

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Project description:BackgroundWomen presenting with signs and symptoms of myocardial ischemia frequently have no or nonobstructive coronary artery disease (CAD).ObjectiveThis study aimed to investigate the associations between angiographic measures and longer-term clinical outcomes among women with signs and symptoms of ischemia referred for coronary angiography.MethodsA prospective cohort analysis of women referred for coronary angiography and enrolled in the National Heart, Lung, and Blood Institute-sponsored WISE was performed. An angiographic severity score was prospectively developed, assigning points for any stenosis weighted by stenosis severity, location, and collaterals and was then tested for prediction for adverse outcome in 917 women, over a median of 9.3 years.SettingThe study was conducted in referral centers.PatientsWomen with signs and/or symptoms of myocardial ischemia referred for coronary angiography were consecutively consented and enrolled in a prospective study.Main outcome measuresMain outcomes included first occurrence of cardiovascular death or nonfatal myocardial infarction. Hospitalization for angina was a secondary outcome.ResultsCardiovascular death or myocardial infarction at 10 years occurred in 6.7%, 12.8%, and 25.9% of women with no, nonobstructive, and obstructive CAD (P < .0001), respectively. Cumulative 10-year cardiovascular death or myocardial infarction rates showed progressive, near-linear increases for each WISE CAD severity score range of 5, 5.1 to 10, 10.1 to 20, 20.1 to 50, and >50. The optimal threshold in the WISE severity score classifications for predicting cardiovascular mortality was >10 (eg, 5.0-10 vs 10.1-89), with both a sensitivity and specificity of 0.64 and an area under the curve of 0.64 (P = .02, 95% CI 0.59-0.68).ConclusionsAmong women with signs and symptoms of ischemia, nonobstructive CAD is common and associated with adverse outcomes over the longer term. The new WISE angiographic score appears to be useful for risk prediction in this population.

Project description:Paraoxonase (PON), a high-density lipoprotein-associated enzyme, is believed to protect against low-density lipoprotein oxidation and thus affects the risk of coronary artery disease (CAD). Three polymorphisms in the PON1 (Leu55Met and Gln192Arg) and PON2 (Ser311Cys) genes have been shown to be associated with the risk of CAD in several European or European-derived populations. In the present study, we examined the associations between these three markers and the severity of CAD as determined by the number of diseased coronary artery vessels in 711 subjects (589 whites and 122 blacks) from the Women's Ischemia Syndrome Evaluation (WISE) study. WISE is a National Heart, Lung, and Blood Institute-sponsored multicenter study designed to address issues related to ischemic-heart-disease recognition and diagnosis in women. Subjects were classified as having normal/minimal CAD (<20% stenosis), mild CAD (20%-49% stenosis), and significant CAD (>/=50% stenosis). The women who had >/=50% stenosis were further classified into groups with one-, two-, or three-vessel disease if any of the three coronary arteries had diameter stenosis >/=50%. No significant association was found between the PON polymorphisms and stenosis severity in either white or black women. However, among white women, when data were stratified by the number of diseased vessels, the frequency of the PON1 codon 192 Arg/Arg genotype was significantly higher in the group with three-vessel disease than in the other groups (those with one-vessel and two-vessel disease) combined (17.02% vs. 4.58%; P=.0066). Similarly, the frequency of the PON2 codon 311 Cys/Cys genotype was significantly higher in the group with three-vessel disease than in the other groups combined (15.22% vs. 4.61%; P=.018). The adjusted odds ratios for the development of three-vessel disease were 2.80 (95% confidence interval 1.06-7.37; P=.038) for PON1 codon 192 Arg/Arg and 3.68 (95% confidence interval 1.26-10.68; P=.017) for PON2 codon 311 Cys/Cys. Our data indicate that the severity of CAD, in terms of the number of diseased vessels, may be affected by common genetic variation in the PON gene cluster, on chromosome 7.

Dataset Information

A randomized controlled trial of low-dose hormone therapy on myocardial ischemia in postmenopausal women with no obstructive coronary artery disease: results from the National Institutes of Health/National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

Background

Methods and results

Conclusions

Publications

A randomized controlled trial of low-dose hormone therapy on myocardial ischemia in postmenopausal women with no obstructive coronary artery disease: results from the National Institutes of Health/National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

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