Sally A. Shumaker

Effects of estrogen replacement on the progression of coronary-artery atherosclerosis

Background Heart disease is a major cause of illness and death in women. To understand better the role of estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects. Methods We randomly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of conjugated estrogen per day, 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (±SD) of 3.2±0.6 years. Base-line and follow-up coronary angiograms were analyzed by quantitative methods. Results Estrogen and estrogen plus medroxyprogesterone acetate produced significant reductions in low-density lipoprotein cholesterol levels (9.4 percent and 16.5 percent, respectively) and significant increases in high-density lipoprotein cholesterol levels (18.8 percent and 14.2 percent, respectively); however,...

Implementation of the women's health initiative study design

The Women’s Health Initiative (WHI) Clinical Trial (CT) includes three overlapping components, each a randomized controlled comparison among women who were postmenopausal and 50 to 79 years of age at randomization. The dietary modification (DM) component randomly assigned 48,836 (target 48,000) eligible women to either a sustained low-fat eating pattern (40%) or self-selected dietary behavior (60%), with breast cancer and colorectal cancer as designated primary outcomes and coronary heart disease as a secondary outcome. The nutrition goals for women assigned to the DM intervention group have been to reduce total dietary fat to 20%, and saturated fat to less than 7% of daily calories and, secondarily, to increase daily servings of vegetables and fruits to at least five and of grain products to at least six and to maintain these changes throughout trial follow-up. The randomization of 40%, rather than 50%, of participating women to the DM intervention group was intended to reduce trial costs, while testing trial hypotheses with specified power. The postmenopausal hormone therapy (PHT) component comprises two randomized, double-blind trials among 27,347 (target 27,500) women, with coronary heart disease

Gender differences in social support and physical health.

A large body of prospective data has accumulated linking social support to health, and most social scientists agree that low levels of support are associated with poor physical and mental health. Unfortunately, most of the research has been limited to White men. When women and people of color are included in the designs, the relationships between social support and physical health are more complicated. Prospective population-based studies provide evidence that low support is associated with increased risk of mortality in women. However, in several studies, results indicated that, for specific age groups, women with high social support have increased risk of mortality. Factors that may contribute to the observed gender differences in the social support-physical health relationship are discussed. Future research should include adequate numbers of women and more sophisticated measures of social support to move the field forward.

Symptom Relief and Side Effects of Postmenopausal Hormones: Results From the Postmenopausal Estrogen/Progestin Interventions Trial

Objective To assess pair-wise differences between placebo, estrogen, and each of three estrogen-progestin regimens on selected symptoms. Methods This was a 3-year, multicenter, double-blind, placebo-controlled trial in 875 postmenopausal women aged 45–64 years at baseline. Participants were assigned randomly to one of five groups: 1) placebo, 2) daily conjugated equine estrogens, 3) conjugated equine estrogens plus cyclical medroxyprogesterone acetate, 4) conjugated equine estrogens plus daily medroxyprogesterone acetate, and 5) conjugated equine estrogens plus cyclical micronized progesterone. Symptoms were self-reported using a checklist at 1 and 3 years. Factor analysis reduced 52 symptoms to a set of six symptom groups. Results In intention-to-treat analyses at 1 year, each active treatment demonstrated a marked, statistically significant, protective effect against vasomotor symptoms compared with placebo (odds ratios [ORs] 0.17–0.28); there was no additional benefit of estrogen-progestin over estrogen alone. Only progestin-containing regimens were significantly associated with higher levels of breast discomfort (OR 1.92–2.27). Compared with placebo, women randomized to conjugated equine estrogens reported no increase in perceived weight. Those randomized to medroxyprogesterone acetate reported less perceived weight gain (OR 0.61–0.69) than placebo. Anxiety, cognitive, and affective symptoms did not differ by treatment assignment. Analyses restricted to adherent women were not materially different than those using intention-to-treat, except that women adherent to medroxyprogesterone acetate and micronized progesterone regimens reported fewer musculoskeletal symptoms (OR 0.62–0.68). Conclusion These results confirm the usefulness of postmenopausal hormone therapy for hot flashes, show convincingly that estrogen plus progestin causes breast discomfort, and demonstrate little influence of postmenopausal hormones on anxiety, cognition, or affect.

The Women’s Health Initiative Memory Study (WHIMS): A Trial of the Effect of Estrogen Therapy in Preventing and Slowing the Progression of Dementia

Evidence from animal, human cross-sectional, case-control, and prospective studies indicate that hormone replacement therapy (HRT) is a promising treatment to delay the onset of symptoms of dementia. The Womens Health Initiative Memory Study (WHIMS) is the first double-masked, randomized, placebo-controlled, long-term clinical trial designed to test the hypothesis that HRT reduces the incidence of all-cause dementia in women aged 65 and older. WHIMS, an ancillary study to the Womens Health Initiative (WHI) funded by the National Institutes of Health, will recruit a subgroup of women aged 65 and older from among those enrolling in the HRT trial of the WHI. The WHI clinical centers and 10 affiliated satellites plan to enroll approximately 8300 women into WHIMS over a 2-year period. Participants will be followed annually for 6 years, receiving cognitive assessments via the Modified Mini-Mental State (3MS) Examination. Women who screen positively for cognitive impairment on the basis of an educational and age-adjusted 3MS cutpoint proceed to more extensive neuropsychological testing and neurologic evaluation. Each woman suspected to have dementia then undergoes a series of laboratory tests that confirm the clinical diagnosis and classify the type of dementia. WHIMS is designed to provide more than 80% statistical power to detect a 40% reduction in the rate of all-cause dementia, an effect that could have profound public health implications for older womens health and functioning.

Assessment of quality of life as observed from the baseline data of the Studies of Left Ventricular Dysfunction (SOLVD) trial quality-of-life substudy

The improvement of aspects of a patients quality of life may be as important as prolonging survival in evaluating clinical trials of heart failure. The purpose of this study was to analyze the psychometric properties of the baseline measures from the quality-of-life substudy from the Studies of Left Ventricular Dysfunction (SOLVD) trial. The measures included the 6-Minute Walk Test, Dyspnea Scale, Living with Heart Failure, Physical Limitations, Psychologic Distress and Health Perceptions, as reported by both patients and staff. Cognitive functioning, such as Vocabulary, Digit Span and Trails Making, was also assessed. Patients were classified as New York Heart Association class I (n = 158) versus II or III (n = 150). The internal consistencies (i.e., reliabilities) of the self-report measures were high, except for the Health Perceptions of Class II or III patients. Reliability of the SOLVD quality-of-life battery was confirmed by significantly better life quality among New York Heart Association class I patients versus class II or III patients combined on the Walk Test, Physical Limitations, Dyspnea, Living with Heart Failure, Psychologic Distress and staff perceptions of patient health. In accordance with prior studies, the measures were uncorrelated with left ventricular ejection fraction. By demonstrating strong internal consistencies, reliability based on physician reports, and independence of ejection fraction levels, use of this quality-of-life assessment battery in this and other clinical trials of compromised ventricular functioning is supported.

Social support and cardiovascular disease

Key Concepts: An Introduction to Cardiovascular Disease D.M. Davidson. Measures of Health Outcome in Social Support Research R.M. Kaplan. Establishing a Relationship between Social Support and Cardiovascular Disease: International Epidemiological Evidence for a Relationship between Social Support and Cardiovascular Disease K. Orth-Gomer. A Critical Evaluation of United States Epidemiological Evidence, Including a Special Consideration of Ethnic Variation H.P. Hazuda. Individual, Environmental, and Cultural Factors in Social Support and Cardiovascular Disease: Gender Differences in Type A Behavior, Social Support, and Ischemic Heart Disease M.A. Morell, et al. Social Support in the Work Environment and Cardiovascular Disease J.V. Johnson, E.M. Hall. The Development of Cardiovascular Disease: Social Support and Coronary Heart Disease S. Cohen, et al. The Crisis and Rehabilitation Phases of Cardiovascular Disease: Cardiac Rehabilitation K. Dracup. 7 additional articles. Index.

Quality-of-life Among 5,025 Patients With Left-ventricular Dysfunction Randomized Between Placebo and Enalapril - the Studies of Left-ventricular Dysfunction

Objectives. This study was performed to assess the quality of life of patients with left ventricular dysfunction for up to 2 years after randomization to enalapril or placebo. Background. Previous reports have documented that survival of patients with congestive heart failure can be extended by the angiotensin-converting enzyme inhibitor enalapril. However, it is unknown whether enalapril has a long-term favorable impact on the quality of life in patients with heart failure. Methods. A brief quality of life questionnaire assessing the quality of life was administered at baseline and at 6 weeks, 1 year and 2 years of follow-up to patients randomized to placebo or enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). Participants had an ejection fraction less than or equal to 0.35, no other serious illnesses and either symptomatic heart failure (treatment trial, n = 2,465) or asymptomatic left ventricular dysfunction (prevention trial, n = 2,560). Results. Among the 14 scales of quality of life, better scores at one or more follow-up intervals were noted in 6 scales in the treatment trial and in 1 scale in the prevention trial among patients assigned to enalapril. Consistent superiority with enalapril at two consecutive follow-up intervals was noted in the treatment trial for social functioning and dyspnea but for no scale in the prevention trial. However, an average of 40% of quality of life responses were missing at 2 years of follow-up because of death or failure to complete the questionnaire. In the treatment trial, survivors with more severe heart failure were less likely to complete the questionnaire. Conclusions. Modest benefits in quality of life for greater than or equal to 1 year occurred when patients with left ventricular dysfunction and symptomatic heart failure were treated with enalapril. No apparent beneficial or adverse effect on quality of life was observed with enalapril in asymptomatic patients with left ventricular dysfunction.

Factors Related to Sleep Disturbance in Older Adults Experiencing Knee Pain or Knee Pain with Radiographic Evidence of Knee Osteoarthritis

OBJECTIVES: To describe the types and frequencies of sleep complaints and the biopsychosocial factors associated with sleep disturbance in a large community sample of older adults experiencing knee pain or knee pain with radiographic evidence of knee osteoarthritis (OA).

Reliability and Validity of the Women's Health Initiative Insomnia Rating Scale

The reliability and construct validity of the 5-item Womens Health Initiative Insomnia Rating Scale (WHIIRS) were evaluated in 2 studies. In Study 1, using a sample of 66,269 postmenopausal women, validity of the WHIIRS was assessed by examining its relationship to other measures known to be related to sleep quality. Reliability of the WHIIRS was estimated using a resampling approach; the mean alpha coefficient was .78. Test-retest reliability coefficients were .96 for same-day administration and .66 after a year or more. Correlations of the WHIIRS with the other measures were in the predicted directions. Study 2 used a sample of 459 women and compared the WHIIRS with objective indicators of sleep quality. Results showed that differences in the objective indicators could be detected by the WHIIRS. Findings suggest that a between-group mean difference of approximately 0.50 of a standard deviation on the WHIIRS may be clinically meaningful.