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Author(s): Hedlin, Haley; Weitlauf, Julie; Crandall, Carolyn J; Nassir, Rami; Cauley, Jane A; Garcia, Lorena; Brunner, Robert; Robinson, Jennifer; Stefanick, Marica L; Robbins, John | Abstract: Objective:The aim of the study was to develop a web-based calculator that predicts the likelihood of experiencing multiple, competing outcomes prospectively over 5, 10, and 15 years.Methods:Baseline demographic and medical data from a healthy and racially and ethnically diverse cohort of 161,808 postmenopausal women, aged 50 to 79 at study baseline, who participated in the Women's Health Initiative (WHI), were used to develop and evaluate a risk-prediction calculator designed to predict individual risk for morbidity and mortality outcomes. Women were enrolled from 40 sites arranged in four regions of the United States. The calculator predicts all-cause mortality, adjudicated outcomes of health events (ie, myocardial infarction [MI], stroke, and hip fracture), and disease (lung, breast, and colorectal cancer). A proportional subdistribution hazards regression model was used to develop the calculator in a training dataset using data from three regions. The calculator was evaluated using the C-statistic in a test dataset with data from the fourth region.Results:The predictive validity of our calculator measured by the C-statistic in the test dataset for a first event at 5 and 15 years was as follows: MI 0.77, 0.61, stroke 0.77, 0.72, lung cancer 0.82, 0.79, breast cancer 0.60, 0.59, colorectal cancer 0.67, 0.60, hip fracture 0.79, 0.76, and death 0.74, 0.72.Conclusion:This study represents the first large-scale study to develop a risk prediction calculator that yields health risk prediction for several outcomes simultaneously. Development of this tool is a first step toward enabling women to prioritize interventions that may decrease these risks. : Video Summary:http://links.lww.com/MENO/A463.

Objective: Psychological traits such as optimism and hostility affect coronary heart disease (CHD) risk, but mechanisms for this association are unclear. We hypothesized that optimism and hostility may affect CHD risk via changes in heart rate variability (HRV).Methods: We conducted a longitudinal analysis using data from the Women's Health Initiative Myocardial Ischemia and Migraine Study. Participants underwent 24-hour ambulatory electrocardiogram monitoring 3 years after enrollment. Optimism (Life Orientation Test-Revised), cynical hostility (Cook-Medley), demographics, and coronary risk factors were assessed at baseline. HRV measures included standard deviation of average N-N intervals (SDNN); standard deviation of average N-N intervals for 5 minutes (SDANN); and average heart rate (HR). CHD was defined as the first occurrence of myocardial infarction, angina, coronary angioplasty, and bypass grafting. Linear and Cox regression models adjusted for CHD risk factors were used to examine, respectively, associations between optimism, hostility, and HRV and between HRV and CHD risk.Results: Final analyses included 2655 women. Although optimism was not associated with HRV, hostility was inversely associated with HRV 3 years later (SDANN: adjusted β = -0.54; 95% CI = -0.97 to -0.11; SDNN: -0.49; 95% CI = -0.93 to -0.05). HRV was inversely associated with CHD risk; for each 10-millisecond increase in SDNN or SDANN, there was a decrease in CHD risk of 9% (p = .023) and 12% (p = .006), respectively.Conclusions: HRV did not play a major role in explaining why more optimistic women seem to be somewhat protected from CHD risk. Although hostility was inversely associated with HRV, its role in explaining the association between hostility and CHD risk remains to be established.

Background physical and mental health are important risk factors for cardiovascular disease (CVD) incidence and death among postmenopausal women. The objective of this study was to assess whether changes in physical and mental health were associated with CVD incidence and death. Methods in the Women’s Health Initiative Observational Study, 48,906 women (50–79 years) had complete data at baseline on physical and mental health (assessed with Short Form-36) and key covariates. Changes in self-reported physical and mental health were calculated between baseline and year 3. Incident CVD and death between year 3 and end of the study were verified with medical records. Results over a median 8.2-year follow-up, 2,319 women developed CVD, and 1,571 women died, including 361 CVD deaths. Women with continued poor health and those with worsened health had significantly increased risk of CVD incidence, CVD-specific death and all-cause death relative to women with continued good health. Both major and minor declines in physical health were associated with an increased risk of these outcomes relative to women with no change in physical health. Only major declines in mental health were associated with poor prognosis. Conclusions changes in physical and mental health over 3 years were independently associated with subsequent CVD events.

Background/Objective Many studies have shown a U-shaped association of sleep duration with mortality; however, this association is difficult to interpret owing to possible reverse causation, residual confounding, and measurement issues. We used data from the Women's Health Initiative to examine the associations of sleep duration, insomnia, and use of sleep aids with death from cardiovascular disease (CVD), cancer, “other” causes, and all causes combined. Methods Cox proportional hazards models were used in the analysis of baseline data and in time-dependent analyses of repeated measures to estimate associations of sleep-related factors with mortality. Among 158,203 women with information regarding sleep, 30,400 total deaths, 8857 CVD deaths, 9284 cancer deaths, and 11,928 other deaths were ascertained over a median of 17.8 years. Results In both baseline and time-dependent analyses, both short (≤5 h) and long sleep (≥9 h) durations were associated with increased risk of total, CVD, and “other” deaths, but not with cancer deaths. Insomnia showed no association with mortality, whereas use of sleep medications was associated with an increased mortality risk. Conclusions While our findings showed a small but robust association of sleep duration with mortality in postmenopausal women, studies including objective measurements of sleep quality and efficiency are needed to clarify these associations.

Objectives To examine prospective associations between changes in physical activity (PA) and changes in physical performance measures (PPMs) over 6 years in older women. Design Prospective cohort study. Setting Forty clinical centers in the United States. Participants Women aged 65 and older (mean age 69.8) enrolled in the Women's Health Initiative Clinical Trials with gait speed, timed chair stand, grip strength, and self-reported recreational PA data assessed at baseline (1993–98) and follow-up Years 1, 3, and 6 (N = 5,092). Measurements Mixed-effects linear regression models were used to determine the association between time-varying PA and change in each PPM. Potential interactions between time-varying PA and age (

Author(s): Zaslavsky, Oleg; Zelber-Sagi, Shira; LaCroix, Andrea Z; Brunner, Robert L; Wallace, Robert B; Cochrane, Barbara B; Woods, Nancy F | Abstract: BackgroundWe compared the simplified Women's Health Initiative (sWHI) and the standard Cardiovascular Health Study (CHS) frailty phenotypes in predicting falls, hip fracture, and death in older women.MethodsParticipants are from the WHI Clinical Trial. CHS frailty criteria included weight loss, exhaustion, weakness, slowness, and low physical activity. The sWHI frailty score used two items from the RAND-36 physical function and vitality subscales, one item from the WHI physical activity scale plus the CHS weight loss criteria. Specifically, level of physical function was the capacity to walk one block and scored as severe (2-points), moderate (1-point), or no limitation (0). Vitality was based on feeling tired most or all of the time (1-point) versus less often (0). Low physical activity was walking outside less than twice a week (1-point) versus more often (0). A total score of 3 resulted in a frailty classification, a score of 1 or 2 defined pre-frailty, and 0 indicated nonfrailty. Outcomes were modeled using Cox regression and Harrell C-statistics were used for comparisons.ResultsApproximately 5% of the participants were frail based on the CHS or sWHI phenotype. The sWHI frailty phenotype was associated with higher rates of mortality (hazard ratio [HR] = 2.36, p ≤ .001) and falls (HR = 1.45, p = .005). Comparable HRs in CHS-phenotype were 1.97 (p l .001) and 1.36 (p = .03), respectively. Neither phenotype predicted hip fracture. Harrell C-statistics revealed nonsignificant differences in HRs between the CHS and sWHI frailty phenotypes.ConclusionThe sWHI phenotype, which is self-reported and brief, might be practical in settings with limited resources.

Older adults have physical and social barriers to eating but whether this affects functional status is unknown. We examined associations between eating barriers and physical function in the Women’s Health Initiative (WHI). In 2012-14, a subset of alive and participating women (n=5910) completed an in-home examination including the Short Physical Performance Battery (SPPB) (grip strength, balance, timed walking speed, chair stand). WHI participants complete annual mailed questionnaires; the 2013-14 questionnaire included items on eating alone, eating < two meals/day, dentition problems affecting eating, physical difficulties with cooking/shopping and monetary resources for food. Linear regression tested associations of these eating barriers with SPPB, adjusting for BMI, age, race/ethnicity, and medical multimorbidities. Over half (56.8%) of participants were ≥ 75 years, 98.8% had a BMI ≥ 25.0 kg/m(2) and 66% had multimorbidities. Eating barriers, excluding eating alone, were associated with significantly lower total (all p

OBJECTIVE: To examine associations of parental ages at childbirth with healthy survival to age 90 years among older women. STUDY DESIGN: This study included a racially and ethnically diverse sub-cohort of 8,983 postmenopausal women from the larger Women’s Health Initiative population, recruited during 1993–1998 and followed for up to 25 years through 2018. MAIN OUTCOME MEASURES: The outcome was categorized as: 1) healthy survival, defined as survival to age 90 without major morbidities (coronary heart disease, stroke, diabetes, cancer, or hip fracture) or mobility disability; 2) usual survival, defined as survival to age 90 without healthy aging (reference category); or 3) death before age 90. Women reported their own and their parents’ birth years, and parental ages at childbirth were calculated and categorized as

ObjectivesTo compare the ability of the commonly used Women's Health Initiative (WHI) and Cardiovascular Health Study (CHS) frailty phenotypes to predict falls, hip fracture, and death in WHI Clinical Trial participants aged 65 and older.DesignLongitudinal cohort study.SettingWHI Clinical Trial.ParticipantsParticipants with data for WHI and CHS frailty phenotypes (N = 3,558).MeasurementsFrailty was operationally defined in the CHS as the presence of three or more of weight loss, poor energy, weakness, slowness, and low physical activity. WHI operationalized frailty similarly but with the RAND-36 physical function scale substituted for slowness and weakness (RAND-36 physical function scale score 78 = 0 points). Frailty was defined as a summary score of 3 or greater, prefrailty as a score of 2 or 1, and nonfrailty as a score of 0. Outcomes were modeled using Cox regression. Harrell C-statistics were compared for models containing alternative instruments.ResultsApproximately 5% of participants were frail based on the CHS or WHI phenotype. The WHI frailty phenotype was associated with higher rates of falls (hazard ratio (HR) = 1.48, P = .003), hip fracture (HR = 1.87, P = .04), and death (HR = 2.32, P < .001). Comparable HRs in CHS-phenotype frail women were 1.32 (P = .04), 1.08 (P = .83), and 1.91 (P < .001), respectively. Harrell C-statistics revealed marked but insignificant differences in predicting abilities between CHS and WHI phenotype models (P > .50 for all).ConclusionThe WHI phenotype, which does not require direct measurements of physical performance, might offer a practical advantage for epidemiological and clinical needs.

Background The number of older adults living to age 80 and older is increasing rapidly, particularly among women. Correlates of quality of life (QOL) in very advanced ages are not known. We examined the association of demographic, social-psychological, lifestyle, and physical health variables with global QOL in a Women's Health Initiative (WHI) cohort of women aged 80 and older. Methods 26,299 WHI participants, who had completed a recent psychosocial and medical update, were included in these analyses. Global QOL was assessed by a single item, asking the women to rate their overall QOL on a scale from 0 to 10. Characteristics of the women were examined by the level of their transformed global QOL scores (≤50, 50-70, ≥70), and multiple regression was used to examine which demographic, social-psychological, lifestyle and health variables were independently associated with higher global QOL. Results Social-psychological and current health variables were more strongly associated with global QOL than a history of selected comorbid conditions. In particular, higher self-rated health and fewer depressive symptoms were the most strongly associated with better global QOL in WHI women ≥80 years. Conclusions Interventions to reduce depressive symptoms and improve health may lead to better self-reported health and global QOL among older women. Physical and mental health screenings followed by evidence-based interventions are imperative in geriatric care.

Background Intensive dietary intervention programs may lead to benefits in vitality and other components of health quality. The Women's Health Initiative Dietary Modification (DM) intervention includes a large randomized controlled trial of an intensive intervention. Objective To evaluate whether the intervention is associated with improved health-related quality of life (HRQoL) subscales, overall self-reported health, depression symptoms, cognitive functioning, and sleep quality. Design This randomized controlled trial was analyzed as intent to treat. Participants Between 1993 and 1998, 48,835 women aged 50 to 79 years were recruited by 40 clinical centers across the United States. Eligibility included having fat intake at baseline ≥32% of total calories, and excluded women with any prior colorectal or breast cancer, recent other cancers, type 1 diabetes, or medical conditions with predicted survival Intervention Goals were to reduce calories from fat to 20%, increase vegetables and fruit to 5+ servings, and increase grain servings to 6+ servings a day. During the first year, 18 group sessions were held, with quarterly sessions thereafter. Main outcome measures The RAND 36-Item Health Survey was used to assess HRQoL at baseline, Year 1, and close-out (about 8 years postrandomization), and estimate differential HRQoL subscale change scores. Statistical analyses performed Mean change in HRQoL scores (Year 1 minus baseline) were compared by randomization group using linear models. Results At 1 year, there was a differential change between intervention and comparison group of 1.7 units (95% CI 1.5, 2.0) in general health associated with the intervention. DM intervention improved physical functioning by 2.0 units (95% CI 1.7, 2.3), vitality by 1.9 units (95% CI 1.6, 2.2), and global quality of life by 0.09 units (95% CI 0.07, 0.12). With the exception of global quality of life, these effects were significantly modified by body mass index at baseline. Conclusions DM intervention was associated with small, but significant improvements in three HRQoL subscales: general health, physical functioning, and vitality at 1 year follow-up, with the largest improvements seen in the women with the greatest baseline body mass index.

Author(s): Shadyab, Aladdin H; Manson, JoAnn E; Li, Wenjun; Gass, Margery; Brunner, Robert L; Naughton, Michelle J; Cannell, Brad; Howard, Barbara V; LaCroix, Andrea Z | Abstract: Objective:to examine the association of parental longevity with healthy survival to age 90 years. Methods:this was a prospective study among a racially and ethnically diverse cohort of 22,735 postmenopausal women from the Women's Health Initiative recruited from 1993 to 1998 and followed through 2017. Women reported maternal and paternal ages at death and current age of alive parents. Parental survival categories were l70, 70-79 (reference), 80-89 and ≥90 years (longevity). Healthy ageing was defined as reaching age 90 without major chronic conditions (coronary heart disease, stroke, diabetes, cancer, or hip fracture) or physical limitations. Results:women whose mothers survived to ≥90 years were more likely to attain healthy ageing (OR, 1.25; 95% CI, 1.11-1.42) and less likely to die before age 90 (OR, 0.75; 95% CI, 0.68-0.83). Women whose fathers survived to ≥90 years did not have significantly increased odds of healthy ageing but showed 21% (OR, 0.79; 95% CI, 0.70-0.90) decreased odds of death before age 90. Women whose mother and father both lived to 90 had the strongest odds of healthy ageing (OR, 1.38; 95% CI, 1.09-1.75) and decreased odds of death (OR, 0.68; 95% CI, 0.54-0.85). The proportion of healthy survivors was highest among women whose mother and father lived to 90 (28.6%), followed by those whose mother only lived to 90 (23.2%). Conclusions:parental longevity predicted healthy ageing in a national cohort of postmenopausal women, supporting the view that genetic, environmental, and behavioral factors transmitted across generations may influence ageing outcomes among offspring.

Background Epidemiologic studies suggest a strong link between poor habitual sleep quality and increased cardiovascular disease risk. However, the underlying mechanisms are not entirely clear. Metabolomic profiling may elucidate systemic differences associated with sleep quality that influence cardiometabolic health. Methods We explored cross-sectional associations between sleep quality and plasma metabolites in a nested case–control study of coronary heart disease (CHD) in the Women’s Health Initiative (WHI; n = 1956) and attempted to replicate the results in an independent sample from the Nurses’ Health Study II (NHSII; n = 209). A sleep-quality score (SQS) was derived from self-reported sleep problems asked in both populations. Plasma metabolomics were assayed using LC–MS with 347 known metabolites. General linear regression was used to identify individual metabolites associated with continuous SQS (false-discovery rate Results After adjusting for age, race/ethnicity, body mass index (BMI) and smoking, we identified 69 metabolites associated with SQS in the WHI (59 were lipids). Of these, 16 were replicated in NHSII (15 were lipids), including 6 triglycerides (TAGs), 4 phosphatidylethanolamines (PEs), 3 phosphatidylcholines (PCs), 1 diglyceride (DAG), 1 lysophosphatidylcholine and N6-acetyl-L-lysine (a product of histone acetylation). These metabolites were consistently higher among women with poorer sleep quality. The LASSO selection resulted in a nine-metabolite score (TAGs 45: 1, 48: 1, 50: 4; DAG 32: 1; PEs 36: 4, 38: 5; PCs 30: 1, 40: 6; N6-acetyl-L-lysine), which was positively associated with CHD risk (odds ratio per SD increase in the score: 1.16; 95% confidence interval: 1.05, 1.28; p = 0.0003) in the WHI after adjustment for matching factors and conventional CHD risk factors. Conclusions Differences in lipid metabolites may be an important pathogenic pathway linking poor habitual sleep quality and CHD risk.

Introduction Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. Methods We conducted a prospective study on 7444 community-dwelling women (aged 65–80 y) with self-reported sleep duration, within the Women's Health Initiative Memory Study in 1995–2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. Results We found a statistically significant ( P = .03) V-shaped association with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs. 7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. Discussion In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors.

Objectives: This study assessed whether the physical component summary score of the RAND-36 health-related quality-of-life survey was associated with incidence of coronary heart disease, stroke, congestive heart failure, angina, or peripheral arterial disease, and whether baseline chronic conditions modified these associations. Methods: Analysis was limited to 69,155 postmenopausal women (50–79 years) in the Women’s Health Initiative Study who had complete data on the RAND-36, the outcomes, and covariates. Chronic conditions were defined as blood pressure ⩾140/90 mm or self-reported heart disease, diabetes, hypertension, arthritis, asthma, emphysema, cancer, and/or cholesterol-reducing medication use. Outcomes data were ascertained during follow-up (1993–2005) with medical records. Results: There were 2451 coronary heart disease, 1896 stroke, 1533 congestive heart failure, 1957 angina, and 502 peripheral arterial disease events during follow-up (median 8.2 years). Participants in the lowest physical component summary quintile, compared to the highest, had a significantly higher risk of developing coronary heart disease (hazard ratio (95% confidence interval) 2.0 (1.7, 2.3)), stroke (1.8 (1.5, 2.2)), angina (2.4(2.0, 2.9)), and peripheral arterial disease (3.0 (2.0, 4.4)), irrespective of chronic conditions. Interactions between physical component summary and existing chronic conditions were not significant for any outcome except congestive heart failure (p = 0.005); after adjustment, participants in the lowest physical component summary quintile and with any chronic condition had nearly a twofold higher risk of congestive heart failure (Yes = 4.4 (3.3, 5.8) vs No = 2.4 (1.2, 4.3)). Conclusion: We found a low physical component summary score was a significant risk factor for individual cardiovascular disease incidence in postmenopausal women.

Author(s): Stefanick, Marcia L; Brunner, Robert L; Leng, X; Limacher, Marian C; Bird, Chloe E; Garcia, David O; Hogan, Patricia E; LaMonte, Michael J; Mackey, Rachel H; Johnson, Karen C; LaCroix, Andrea; Robinson, Jennifer G; Seguin, Rebecca A; Tindle, Hilary A; Wassertheil-Smoller, Sylvia | Abstract: BackgroundCardiovascular disease (CVD) is highly prevalent at ages 80 and above. The association of physical functioning (PF), a key to an optimal aging trajectory, with CVD and specific CVD diagnosis in women who survive to age 80 and above has not been described previously and has important public health significance given our aging population.MethodsWomen's Health Initiative participants aged 80 years or older at the time of self-reporting PF (RAND SF-36) were studied in relationship to CVD diagnosis, whether present at study baseline (1993-1998) or diagnosed during follow-up through 2012. Cross-sectional analyses utilized demographic, medical, lifestyle, and psycho-social questionnaire data from baseline or updated at the time of self-reported PF.ResultsAmong 27,145 older Women's Health Initiative participants, 22.0% (N = 5,959) had been diagnosed with CVD, specifically: 11.3% (N = 3,071) with coronary heart disease; 4.7% (N = 1,279), stroke; 5.2% (N = 1,397), venous thromboembolism; 2.7% (N = 737), peripheral arterial disease; and 2.7% (N = 725), congestive heart failure. PF scores (mean ± SE) were significantly (p l .0001) higher without CVD (60.0 ± 26.9), compared with any CVD (47.9 ± 27.3), and for each specific CVD diagnosis: coronary heart disease (48.8 ± 27.1); stroke (44.8 ± 27.9); venous thromboembolism (48.9 ± 27.4); peripheral arterial disease (41.9 ± 2.2); and congestive heart failure (38.8 ± 26.1). Regardless of CVD diagnosis, higher PF was associated with: younger age at the time of PF assessment; lower body mass index; higher recreational physical activity; better self-reported general health; fewer hip fractures after age 55; no history of arthritis; and no recent use of non-steroidal anti-inflammatory drugs.ConclusionsOlder women with any CVD, and particularly women with congestive heart failure or peripheral arterial disease, reported significantly lower PF compared to women with no CVD. Regardless of CVD diagnosis, higher PF was strongly associated with a more active lifestyle and lower body mass index, suggesting potential intervention targets for more optimal aging.

Objective Late-life depressive symptoms (DS) increase the risk of incident mild cognitive impairment and probable dementia in the elderly. Our objectives were to examine the relationship between elevated DS and regional brain volumes including frontal lobe subregions, hippocampus and amygdala, and to determine whether elevated DS were associated with increased subclinical cerebrovascular disease in postmenopausal women. Methods DS were assessed an average of 8 years prior to structural brain MRI in 1372 women. The 8-item Burnam regression algorithm was used to define DS with a cut-point of 0.009. Adjusting for potential confounders, mean differences in total brain, frontal lobe subregions, hippocampus and amygdala volumes and total ischemic lesion volumes in the basal ganglia and the cerebral white and gray matter outside the basal ganglia were compared between women with and without DS. Results Depressed women had lower baseline global cognition and were more likely to have prior hormone therapy history. After full adjustment, DS at baseline were associated with smaller superior and middle frontal gyral volumes. Hippocampal and amygdala volumes, and ischemic lesion volumes were similar in depressed and non-depressed women. Limitations Depression was not assessed based on semi-structured interview, and MRI scans were obtained cross-sectionally rather than longitudinally. Longitudinal MRI assessments will be necessary to define the temporal relationships between DS and frontal lobe volumes. Conclusions Elevated DS were associated with lower volumes in certain frontal lobe subregions but not in the medial temporal lobe structures. Our findings support the role of frontal lobe structures in late-life DS among women.

Use of conjugated equine estrogens (CEE) has been linked to smaller regional brain volumes in women aged ≥65 years; however, it is unknown whether this results in a broad-based characteristic pattern of effects. Structural magnetic resonance imaging was used to assess regional volumes of normal tissue and ischemic lesions among 513 women who had been enrolled in a randomized clinical trial of CEE therapy for an average of 6.6 years, beginning at ages 65-80 years. A multivariate pattern analysis, based on a machine learning technique that combined Random Forest and logistic regression with L(1) penalty, was applied to identify patterns among regional volumes associated with therapy and whether patterns discriminate between treatment groups. The multivariate pattern analysis detected smaller regional volumes of normal tissue within the limbic and temporal lobes among women that had been assigned to CEE therapy. Mean decrements ranged as high as 7% in the left entorhinal cortex and 5% in the left perirhinal cortex, which exceeded the effect sizes reported previously in frontal lobe and hippocampus. Overall accuracy of classification based on these patterns, however, was projected to be only 54.5%. Prescription of CEE therapy for an average of 6.6 years is associated with lower regional brain volumes, but it does not induce a characteristic spatial pattern of changes in brain volumes of sufficient magnitude to discriminate users and nonusers.

OBJECTIVES: To determine whether small decrements in global cognitive function that conjugated equine estrogen (CEE) therapies have been shown to produce in older women persist after cessation and extend to specific cognitive domains. DESIGN: Randomized controlled clinical trial. SETTING: Fourteen clinical centers of the Women's Health Initiative. PARTICIPANTS: Two thousand three hundred four women aged 65 to 80 free of probable dementia at enrollment. INTERVENTION: CEE 0.625 mg/d with or without medroxyprogesterone acetate (MPA, 10 mg/d) and matching placebos. MEASUREMENTS: Annual administrations of a battery of cognitive tests during and after the trial. RESULTS: Assignment to CEE-based therapies was associated with small mean relative decrements in global cognitive function and several domain-specific cognitive functions during the trial, which largely persisted through up to 4 years after the trial. The strongest statistical evidence was for global cognitive function (0.07–standard deviation decrements during (P=.007) and after (P=.01) the trial. For domain-specific scores, the mean decrements were slightly smaller, were less significant, and tended to be larger for CEE-alone therapy. CONCLUSION: CEE-based therapies, when initiated after the age of 65, produce a small broad-based decrement in cognitive function that persists after their use is stopped, but the differences in cognitive function are small and would not be detectable or have clinical significance for an individual woman. Differences in effects between cognitive domains suggest that more than one mechanism may be involved.

Mild cognitive impairment (MCI) is a transitional state between normal cognitive functioning and dementia. A proposed MCI typology classifies individuals by the type and extent of cognitive impairment, yet few studies have characterized or compared these subtypes. Four hundred forty-seven women 65 years of age and older from the Women's Health Initiative Memory Study were classified into the 4 MCI subgroups and a "no impairment" group and compared on clinical, sociodemographic, and health variables. A cognitive deficit in at least 1 domain was present in 82.1% of participants, with most (74.3%) having deficits in multiple cognitive domains. Only 4.3% had an isolated memory deficit, whereas 21.3% had an isolated nonmemory deficit. Of the 112 women who met all MCI criteria examined, the most common subtype was amnestic multidomain MCI (42.8%), followed by nonamnestic multiple domain MCI (26.7%), nonamnestic single domain (24.1%), and amnestic single domain MCI (6.3%). Subtypes were similar with respect to education, health status, smoking, depression, and prestudy and onstudy use of hormone therapy. Despite the attention it receives in the literature, amnestic MCI is the least common type highlighting the importance of identifying and characterizing other nonamnestic and multidomain subtypes. Further research is needed on the epidemiology of MCI subtypes, clinical and biologic differences between them, and rates for conversion to dementia.

SUMMARY Recent behavioral data have demonstrated the importance of maintaining low phenylalanine concentrations beyond early childhood in patients with phenylketonuria, which can be a difficult task, particularly during adolescence. Administration of certain large neutral amino-acids (valine, isoleucine, leucine–VIL) appears to reduce phenylalanine concentrations in the cerebrospinal fluid of humans and in the brain of rats. The present study compared neuropsychological test-performance of six patients with phenylketonuria during periods of VIL administration and periods when this supplement was not given. Although individual responses to VIL were variable, there was an over-all improvement of about 1½ SD in neuropsychological test performance during VIL treatment. Abstract reasoning and tactile motor problem-solving increased more than pure motor performance. RESUME Rapport preliminaire sur iadministration orale de valine, isoleucine et leucine dans la phenylcetonurie Des donnees recentes de comportement ont demontre l'importance de maintenir des concentrations basses de phenylalanine au dela de la premiere enfance chez les malades atteints de phenylcetonurie ce qui peut etre un tâche difficile particulierement durant I'adolescence. L'administration de certains amino-acides neutres de grande taille (valine, isoleucine, leucine- VIL) apparait reduire les concentrations de phenylalanine dans le LCR humain et le cerveau de rat. L'etude presente compare la performance aux tests neuro-psychologiques de six malades atteints de phenylcetonurie durant des periodes d'administration de VIL et des periodes au cours desquelles ce supplement n'etait pas donne. Bien. que les reponses individuelles au VIL aient ete variables, il a ete note une amelioration generate d'environ un ecart-type et demi aux performances de tests neuro-psychologiques durant le traitement de VIL. Le raisonnement abstrait et la solution de problemes tactilo-moteurs ont progresse plus que la performance motrice pure. ZUSAMMENFASSUNG Vorlaufige positive Testergebnisse fur die orale Gabe von Valin, Isoleucin und Leucin bei Phenylketonurie Neue Verhaltensdaten haben gezeigt, das bei Patienten mit Phenylketonurie die Beibehaltung der Phenylalaninarmen Diat uber das fruhe Kindesalter hinaus von groser Wichtigkeit ist, was insbesondere im Adolescentenalter Schwierigkeiten bereiten kann. Die Gabe bestimmter neutraler Aminosauren (Valin, Isoleucin, Leucin–VIL) scheint die Phenylalaninkonzentrationen im Liquor beim Menschen und im Gehirn von Ratten zu reduzieren. Die vorliegende Studie vergleicht neuropsychologische Testergebnisse von sechs Patienten mit Phenylketonurie wahrend Perioden mit VIL Gabe und ohne. Obwohl die individuellen Reaktionen auf VIL unterschiedlich waren, fand sich doch wahrend der VIL Behandlung bei den neuropsychologischen Testergebnissen eine allgemeine Verbesserung um etwa 1½ SD. Abstraktes Denken und die Losung taktiler motorischer Schwierigkeiten verbesserten sich mehr als die rein motorischen Leistungen. RESUMEN Apoyo preliminar para la administracion oral de valina. isoleucina y leucina en la fenilcetonuria Datos recientes sobre el comportamiento han demonstrado la importancia de mantener concentraciones bajas de fenilalanina mas alia de la primera infancia en pacientes con fenilcetonuria, lo que puede ser una tarea dificil, sobre todo en la adolescencia. La admininstracion de ciertos aminoacidos neutros grandes (valina, isoleucina, leucina–VIL) reducen las concentraciones de fenilalanina en el LCR en seres humanos y en el cerebro de ratas. El presente estudio compara los resultados de tests psicologicos en seis pacientes con fenilcetonuria en los periodos de administracion de VIL, con los periodos en que este suplemento no se dio. Aunque las respuestas individuales durante el tratamiento con VIL eran variables, habia en conjunto una mejoria de alrededor de 1½ SD en los tests neuropsicologicos durante el tratamiento con VIL. El razonamianto abstracto y la resolucion de problemas taltil-motores aumentaban mas que la realizacion puramente motora.

Objectives The Women's Health Initiative (WHI) randomized trial of calcium/vitamin D supplementation found reduced bone loss with active treatment compared to placebo. Now we examine whether the treatment affected self-reported physical functioning and objective measures of physical functioning. Design A randomized, double-blind, placebo-controlled trial of 1,000 mg calcium carbonate plus 400 IU vitamin D 3 per day or matching placebo pills. Subjects/setting The study included 33,067 women (50 to 79 years old) at 40 US study centers. Main outcome measures Physical functioning was assessed by questionnaire at enrollment in WHI, 1 year prior to calcium/vitamin D trial randomization and at study close-out (average follow-up 7.1 years). Objective physical performance and self-reported exercise measures were collected at WHI baseline (1 year prior to calcium/vitamin D enrollment) and 2 years and 4 years after calcium/vitamin D trial enrollment in a subsample (n=3,137). Statistical analyses performed Calcium/vitamin D effects were tested in unadjusted and interaction linear models for each of the physical function measures. Covariates were baseline total calcium intake, fracture risk score, treatment arm in the hormone therapy and dietary modification trials (ie, active drug or placebo, low-fat diet intervention or usual diet, respectively) and age. Results Neither intention to treat nor high adherence analyses produced substantial effects of calcium/vitamin D compared to placebo on physical functioning or performance. The interaction analyses also did not result in differences because of calcium/vitamin D. Conclusions As the first long-term randomized trial to examine the effectiveness of calcium and vitamin D in protecting against decline of physical functioning in older women, the results did not support benefit.

BACKGROUND: Osteoporosis and depression may be associated through common physiologic systems or risk factors. OBJECTIVE: To assess the associations between depressive symptoms (Burnam's scale) or antidepressant use and bone outcomes. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 93,676 postmenopausal women (50 to 79 years old) enrolled in the Women's Health Initiative Observational Study. MEASUREMENTS: Self-reported fractures (n = 14,982) (hip [adjudicated], spine, wrist, and "other"). Analyses included 82,410 women with complete information followed on average for 7.4 years. Bone mineral density (BMD) of the hip (n = 4539), spine (n = 4417), and whole body (n = 4502) was measured at baseline and 3 years in women enrolled at 3 densitometry study sites. RESULTS: Overall, there were no statistically significant associations between depressive symptoms or antidepressant therapy and 3-year change in BMD. In a subset of women not using antidepressants, there was a significant difference in whole-body BMD change between women with and without depressive symptoms (P = .05). Depressive symptoms (hazard ratio [HR] 1.08; 95% CI = 1.02 to 1.14) and antidepressant therapy (HR = 1.22; CI = 1.15 to 1.30) independently increased risk of any fracture, the majority of which occurred at "other" anatomic sites. Antidepressant therapy increased the risk of spine fracture (HR = 1.36; CI = 1.14 to 1.63). No associations were observed between depressive symptoms or antidepressant therapy and hip or wrist fracture. CONCLUSION: In this study of postmenopausal women, average age 64, we observed minimal association between depressive symptoms and 3-year changes in either BMD or fracture risk. Antidepressant use was not associated with changes in BMD, but was associated with increased risk of fractures at the spine and "other " anatomic sites.

Background Data on the association between dietary patterns and age-related cognitive decline are inconsistent. Objective To determine whether dietary patterns assessed by the alternate Mediterranean diet score (aMED), the Healthy Eating Index-2010 (HEI-2010), the Alternate Healthy Eating Index 2010 (AHEI-2010), or the Dietary Approach to Stop Hypertension (DASH) diet score are associated with cognitive decline in older women, and to examine whether dietary patterns modify the risk for cognitive decline in women with hypertension. Design Prospective, longitudinal cohort study. Food frequency questionnaires were used to derive dietary patterns at baseline. Hypertension was defined as self-report of current drug therapy for hypertension or clinic measurement of systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. Participants and setting Postmenopausal women (N=6,425) aged 65 to 79 years who participated in the Women's Health Initiative Memory Study and were cognitively intact at baseline. Main outcome measures Cognitive decline was defined as cases of mild cognitive impairment (MCI) or probable dementia (PD). Cases were identified through rigorous screening and expert adjudication. Statistical analyses performed Cox proportional hazards models with multivariable adjustment were used to estimate the relative risk for developing MCI or PD. Results During a median follow-up of 9.11 years, we documented 499 cases of MCI and 390 of PD. In multivariable analyses we did not detect any statistically significant relationships across quintiles of aMED, HEI-2010, DASH, and AHEI-2010 scores and MCI or PD ( P values for trend=0.30, 0.44, 0.23, and 0.45). In women with hypertension, we found no significant association between dietary patterns and cognitive decline ( P values for trend=0.19, 0.08, 0.07, and 0.60). Conclusions Dietary patterns characterized by the aMED, HEI-2010, AHEI-2010, or DASH dietary score were not associated with cognitive decline in older women. Adherence to a healthy dietary pattern did not modify the risk for cognitive decline in women with hypertension.

Author(s): Cauley, Jane A; McTiernan, Anne; Rodabough, Rebecca J; LaCroix, Andrea; Bauer, Douglas C; Margolis, Karen L; Paskett, Electra D; Vitolins, Mara Z; Furberg, Curt D; Chlebowski, Rowan T; Women's Health Initiative Research Group | Abstract: BackgroundDespite experimental observations suggesting that 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) have antitumor activity, clinical studies have reached mixed conclusions about the relationship between statin use and breast cancer risk.MethodsTo investigate associations between potency, duration of use, and type of statin used and risk of invasive breast cancer, we examined data for 156,351 postmenopausal women who were enrolled in the Women's Health Initiative. Information was collected on breast cancer risk factors and on the use of statins and other lipid-lowering drugs. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Statistical tests were two-sided.ResultsOver an average follow-up of 6.7 years, 4383 invasive breast cancers were confirmed by medical record and pathology report review. Statins were used by 11,710 (7.5%) of the cohort. Breast cancer incidence was 4.09 per 1000 person-years (PY) among statin users and 4.28 per 1000 PY among nonusers. In multivariable models, the hazard ratio of breast cancer among users of any statin, compared with nonusers, was 0.91 (95% CI = 0.80 to 1.05, P = .20). There was no trend in risk by duration of statin use, with HR = 0.80 (95% CI = 0.63 to 1.03) for l 1 year of use, HR = 0.99 (95% CI = 0.80 to 1.23) for 1- l 3 years of use, and HR = 0.94 (95% CI = 0.75 to 1.18) for g or = 3 years of use. Hydrophobic statins (i.e., simvastatin, lovastatin, and fluvastatin) were used by 8106 women, and their use was associated with an 18% lower breast cancer incidence (HR = 0.82, 95% CI = 0.70 to 0.97, P = .02). Use of other statins (i.e., pravastatin and atorvastatin) or nonstatin lipid-lowering agents was not associated with breast cancer incidence.ConclusionsOverall statin use was not associated with invasive breast cancer incidence. Our finding that use of hydrophobic statins may be associated with lower breast cancer incidence suggests possible within-class differences that warrant further evaluation.

Background Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking. Methods We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women’s Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case–control study. Results The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P = 0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics. Conclusions Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.)

BACKGROUND Increased mammographic density reduces the sensitivity of screening mammography, is associated with increased breast cancer risk, and may be hormone related. We assessed the effect of estrogen-plus-progestin therapy on mammographic density. METHODS In a racially and ethnically diverse ancillary study of the Women's Health Initiative, we examined data from 413 postmenopausal women who had been randomly assigned to receive daily combined conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (i.e., progestin; 2.5 mg) (n = 202) or daily placebo (n = 211). We assessed the effect of estrogen plus progestin on measured mammographic percent density and abnormal findings over a 1-year and 2-year period. All tests of statistical significance were two-sided and were based on F tests or t tests from mixed-effects models. RESULTS Mean mammographic percent density increased by 6.0% at year 1, compared with baseline, in the estrogen-plus-progestin group but decreased by 0.9% in the placebo group (difference = 6.9%, 95% confidence interval [CI] = 5.3% to 8.5%; P < .001). The mean changes in mammographic density persisted but were attenuated slightly after 2 years, with an absolute increase of 4.9% in the estrogen-plus-progestin group and a decrease of 0.8% in the placebo group (difference = 5.7%, 95% CI = 4.3% to 7.3%; P < .001). These effects were consistent across racial/ethnic groups but were higher among women aged 70-79 years in the estrogen-plus-progestin group (mean increase at year 1 = 11.6%) than in the placebo group (mean decrease at year 1 = 0.1%) (difference of the means = 11.7%, 95% CI = 8.2% to 15.4%; P < .001, comparing across age groups). At year 1, women who were adherent to treatment in the estrogen-plus-progestin group had a mean increase in density of 7.7% (95% CI = 5.9% to 9.5%), and women in the placebo group had a mean decrease in density of 1.1% (95% CI = 0.3% to 1.9%). Use of estrogen plus progestin was associated with an increased risk of having an abnormal mammogram at year 1 (relative risk = 3.9, 95% CI = 1.5 to 10.2; P = .003), compared with placebo, that was not explained by an increase in density. CONCLUSIONS Use of up to 2 years of estrogen plus progestin was associated with increases in mammographic density.

Author(s): Woods, Nancy Fugate; LaCroix, Andrea Z; Gray, Shelly L; Aragaki, Aaron; Cochrane, Barbara B; Brunner, Robert L; Masaki, Kamal; Murray, Anne; Newman, Anne B; Women's Health Initiative | Abstract: ObjectivesTo define frailty using simple indicators; to identify risk factors for frailty as targets for prevention; and to investigate the predictive validity of this frailty classification for death, hospitalization, hip fracture, and activity of daily living (ADL) disability.DesignProspective study, the Women's Health Initiative Observational Study.SettingForty U.S. clinical centers.ParticipantsForty thousand six hundred fifty-seven women aged 65 to 79 at baseline.MeasurementsComponents of frailty included self-reported muscle weakness/impaired walking, exhaustion, low physical activity, and unintended weight loss between baseline and 3 years of follow-up. Death, hip fractures, ADL disability, and hospitalizations were ascertained during an average of 5.9 years of follow-up.ResultsBaseline frailty was classified in 16.3% of participants, and incident frailty at 3-years was 14.8%. Older age, chronic conditions, smoking, and depressive symptom score were positively associated with incident frailty, whereas income, moderate alcohol use, living alone, and self-reported health were inversely associated. Being underweight, overweight, or obese all carried significantly higher risk of frailty than normal weight. Baseline frailty independently predicted risk of death (hazard ratio (HR)=1.71, 95% confidence interval (CI)=1.48-1.97), hip fracture (HR=1.57, 95% CI=1.11-2.20), ADL disability (odds ratio (OR)=3.15, 95% CI=2.47-4.02), and hospitalizations (OR=1.95, 95% CI=1.72-2.22) after adjustment for demographic characteristics, health behaviors, disability, and comorbid conditions.ConclusionThese results support the robustness of the concept of frailty as a geriatric syndrome that predicts several poor outcomes in older women. Underweight, obesity, smoking, and depressive symptoms are strongly associated with the development of frailty and represent important targets for prevention.

This study described differences in vigorous activity participation recalled across the life span, assessed whether reports of past vigorous activity were associated with current participation, and examined factors associated with participation in current vigorous activity among women. After the exclusion of women aged 50– 54 years, the study population included 71,837 multiethnic postmenopausal women aged 55–79 years who were participating in the Women’s Health Initiative Observational Cohort Study, 1993–1998. Vigorous activity was assessed retrospectively for ages 18, 35, and 50 years and currently at enrollment into the study (median age, 65 years). Current participation in vigorous activity (>3 days/week) was low and consistent across racial/ethnic groups (13–16%). The prevalence of vigorous activity declined with age, with the largest decrease in vigorous activity occurring after age 50 years for all racial/ethnic groups. Current vigorous activity was generally higher among women with a lower body mass index, not currently smoking, in excellent general health, and of higher socioeconomic status across racial/ethnic groups. These data suggest that a lower prevalence of vigorous activity in the postmenopausal period is part of a complex of health-related attitudes and behaviors that transcends race/ethnicity. The perimenopausal period may be a critical juncture at which targeted and tailored interventions may help to achieve maintenance of physical activity into the postmenopausal period.

SUMMARY The Northern Nevada HOPES (HIV Outpatient Program, Education, and Services) Clinic provides comprehensive and consultative care to persons living with HIV/AIDS in Reno, Nevada. As a method of tracking clinical data for evaluation purposes, a computer database was designed and implemented in the clinic setting. Analysis of these data permitted an exploration of the relations among client behaviors such as substance abuse and clinical markers of HIV disease progression. Substance abuse was found to be related to a number of indicators of impaired health. The computerized medical data module was found to be a useful tool for evaluation and quality assurance purposes and permitted the quantification of substance abuse behaviors in the clinic population.

Objective Relationships were examined between hostility, weight status, weight cycling, dieting behaviors, and nutrition attitudes. Method Data were derived from the RENO Diet-Heart Study (RDHS), a 5-year prospective natural history (descriptive) study of weight fluctuations, behavior patterns, and cardiovascular (CVD) risk factors. Overweight versus normal-weight and weight-cycling versus non–weight-cycling men and women were compared on overt and covert hostility. Results Overweight subjects scored significantly higher than normal-weight individuals on covert but not overt hostility. Similarly, subjects with a history of weight fluctuation scored significantly higher on covert hostility than subjects without a history of weight cycling. Subjects who reported more hostility scored higher on measures of eating disinhibition, hunger, and dietary helplessness. Discussion The relationships among hostility, dieting behaviors, and nutrition attitudes could not be explained on the basis of general distress alone. The findings supported the hypothesis that the relationship between hostility and health is mediated by the association between hostility and health-related behaviors. © 1999 John Wiley & Sons, Inc. Int J Eat Disord 26: 37–42, 1999.

Despite a longstanding belief that a low-fat diet can reduce the risk of breast cancer, no controlled intervention trials have been reported. This randomized, controlled, primary prevention trial, based on the Women's Health Initiative cohort, enrolled 48,835 postmenopausal women 50 to 79 years of age at 40 U.S. clinical centers in the years 1993-2005. Forty percent of participants received a diet designed to lower the intake of total fat to 20% of energy, provide at least 5 servings daily of fruit and vegetables, and include at least 6 daily servings of grains. There was no explicit weight loss goal. The remaining 60% of women continued on their usual diets. The intervention group took part in an intensive behavioral modification program administered by a specially trained nutritionist. Participants received an individualized goal of total fat grams based on height and were trained to monitor their dietary intake. The comparison women were given informational materials, including dietary guidelines. At baseline, dietary and other variables, including body weight, were nearly identical in the intervention and control groups. Women in the diet group had a small decrease in energy consumption. The difference between groups in change from baseline in the percentage of energy from fat ranged from 10.7% after 12 months to 8.1% at year 6. The intervention group ate more fruits and vegetables, but there was less difference in grain consumption. The annualized incidence rate of invasive breast cancer during an average follow up of 8.1 years was 0.42% in the intervention group and 0.45% in the comparison group. The hazard ratio was 0.91% with a 95% confidence interval of 0.83 to 1.01. Rates of total cancer (excluding non-melanoma skin cancer), breast cancer mortality, and total mortality all were slightly lower for the intervention group, but the differences were not significant at the 0.05 level. Women who actively participated in the dietary intervention program and those consuming a high-fat diet at baseline had lower hazard ratios. The breast cancer risk also was lower in women with a relatively high baseline percentage of energy from fat. Tumor grade and size, lymph node status, and stage of breast cancers all were similar in the intervention and comparison groups. A lower hazard ratio was noted for progesterone receptor-negative tumors, but there was no apparent association with estrogen receptor status. A low-fat diet failed to lessen the risk of invasive breast cancer in this large trial of postmenopausal women during a follow up averaging approximately 8 years. Nevertheless, the trends observed, although not statistically significant, warrant longer-term studies. Any beneficial effects of reduced fat intake might take years to fully emerge.

Randomized trials have indicated that calcium or vitamin D supplements—or both—may slow bone loss in postmenopausal women, but whether the risk of bone fracture is reduced remains uncertain. This study randomly assigned 36,282 postmenopausal women 50 to 79 years of age, who were enrolled in the Women’s Health Initiative clinical trial, to receive either 1000 mg calcium in carbonate form plus 400 IU vitamin D3 daily or placebo and followed them for an average of 7 years. Women on active treatment had levels of 25-hydroxyvitamin D 28% higher than those in placebo recipients. Bone mineral density (BMD) at the hip remained higher than in women assigned to receive placebo. The mean group difference at the ninth annual visit was 1.06%. Annualized rates of fracture per 10,000 person-years in the supplement and placebo groups were 14 and 16, respectively, for hip fracture; 44 and 44 for lower arm/wrist fractures; 14 and 15 for clinical vertebral fractures; and 164 and 170 for all fractures combined. Women assigned to supplements had a 12% lower risk of hip fracture than placebo recipients, but this was not a statistically significant effect. There were no significant group differences in rates of major diseases, including cardiovascular disease and cancer. The hazard ratio for kidney stones in women receiving supplements was 1.17 (95% confidence interval, 1.02–1.34). This finding was not related to a high baseline calcium intake. Gastrointestinal symptoms occurred in approximately 9% to 10% of both groups. In generally healthy postmenopausal women, daily supplements of calcium and vitamin D were associated with modest improvement in bone density at the hip, but did not substantially lower the risk of hip fracture in this large-scale study. Compared with placebo, supplementation did appear to increase the risk of kidney stones.

Objective This study investigated the relationship between eating and weight behaviors and functioning in individuals' families of origin. Method: Subjects were 237 women and 242 men enrolled in the RENO (Relationship of Energy, Nutrition, and Obesity) Diet-Heart Study, a prospective 5-year study of the effects of weight fluctuation on cardiovascular disease risk factors in normal weight and obese adults. Variables of primary interest included subjects' body mass index (BMI), age of onset of obesity, eating attitudes, lack of control while eating, and family functioning. Results: In men, higher family cohesion was related to healthier eating attitudes and better control over eating, controlling for age, BMI, and adaptability, whereas higher adaptability (changing rules and poor leadership) was related to earlier onset of obesity and more disturbed eating attitudes. Cohesion and adaptability were not related to body weight or eating variables in women. Discussion: The lower societal pressure on men to be thin may increase the importance of family factors in influencing their shape and weight. © 1997 John Wiley & Sons, Inc. Int J Eat Disord 22: 213–218, 1997.

Objectives To study natural weight changes and to develop a weight classification system that can identify weight maintainers, gainers, and losers. Design/outcome A prospective, observational study in which weight changes over five annual measurements were evaluated. In the weight classification system used, changes greater than 5lb defined weight maintenance, gain, or loss. Subjects/settings Subjects were healthy, normal-weight and overweight, men and women (mean age=44.1+14.1 years) in the Relationships of Energy, Nutrition, and Obesity to Cardiovascular Disease Risk Study. Prospective data for 385 of the original 508 subjects for whom actual weights were available for each of the 5 years (1985 to 1990) were used to classify and characterize subjects by weight-change categories. Statistical analyses Cross-tabulations (with χ 2 tests) and hierarchical log-linear analyses (with partial χ 2 tests) to examine the relationships of categorical variables; analyses of variance (with F tests) for continuous measures. Results Over the 4-year interval, 46% of subjects were classified as maintainers, 34% as gainers, and 20% as losers. Over shorter 1-year epochs, more subjects were maintainers (62%) and fewer subjects were gainers (22%) or losers (16%). Maintainers had fewer and smaller magnitudes of weight fluctuations and showed fewer deleterious changes in health risk factors than gainers. Applications Weight changes of greater than ±5lb can classify a person as a weight maintainer, gainer, or loser. Although annual weight changes were used in this study, a weight change of more than 5lb between any two points in time may suggest nonmaintenance of weight or weight instability that needs further evaluation.

Data from the Women’s Health Initiative Memory Study (WHIMS) were analyzed to determine whether conjugated equine estrogen (CEE) influences global cognitive function in women 65 to 79 years of age, and to compare its effects with those of CEE plus medroxyprogesterone acetate (MPA). Using a r

Background: Self-rated health (SRH) predicts all-cause mortality in many studies; whereas, SRH has been inconsistently related to disease specific death, at least in part because often carefully documented cause of death is lacking. Methods: Physician-adjudicated cardiovascular disease (CVD), cancer, and other outcomes were evaluated in the Women’s Health Initiative (WHI) multi-ethnic Observational Study (OS) cohort of 93,6756 postmenopausal women, aged 50 to79 years. SRH was assessed by the RAND36 at baseline and three years later. Results: After adjusting for confounders, compared with women reporting excellent health, the risk of all-cause death among women reporting fair/poor health was significantly higher (HR=1.91, CI 1.68, 2.16) during a 7.6 year (1.6) follow-up, as were risks of death from CVD (HR=2.12, CI 1.65, 2.71) and from cancer (HR=1.40, CI, 1.15, 1.69) but not accidental death (HR=1.39, CI 0.69, 2.76). Compared with women whose scores did not change over the initial three years of follow-up, SRH that worsened significantly was associated with higher risk of all-cause (HR=2.06), CVD (HR=1.71) and cancer (HR=2.22) mortality; whereas, women with improved SRH had significantly lower all-cause, CVD and cancer mortality risks (HR: 0.78, 0.80, and 0.79, respectively). Conclusions: Low SRH and a decrease in SRH over three years were strongly associated with increased risks of all-cause, CVD, cancer and other cause mortality after more than 7 years of follow-up in post-menopausal women. Lower SRH was also associated with incident CVD and cancer

Objective: The primary purpose of this study was to compare obese versus nonobese adults and weight cyclers versus maintainers on measures of dietary helplessness, nutrition concern, dietary restraint, and disinhibition. Method: Dietary helplessness, nutrition concern, dietary restraint, and disinhibition were assessed in 385 healthy obese and nonobese men and women in the RENO Diet-Heart Study, a 5-year prospective investigation of cardiovascular risk factors, weight cycling, and lifestyle. Results: The results indicated that dietary helplessness and disinhibition were significantly greater in obese individuals, subjects with a history of weight cycling, and weight fluctuators (prospectively measured). Women were found to score significantly higher than men on measures of dietary helplessness, disinhibition, and cognitive restraint. Discussion: The role of nutrition attitudes is discussed in relation to dietary self-regulation, weight fluctuation, and management of body weight. © 1995 by John Wiley & Sons, Inc.

This investigation attempted to determine psychological correlates of weight fluctuation in a sample of 497 normal weight and obese adults who were enrolled in a prospective, natural history study. Subjects were stratified by gender, obesity, and age and classified as weight maintainers, gainers, or losers based on their changes in weight over a 1-year period. Subjects were further classified as either weight fluctuators or nonfluctuators based on historical self-report. Nonfluctuators reported significantly higher general well-being, greater eating self-efficacy, and lower stress than weight fluctuators, regardless of body weight. Weight maintainers had more favorable eating self-efficacy related to negative affect than weight gainers. Results suggest that weight fluctuation is strongly associated with negative psychological attributes in both normal weight and obese individuals. Future research should focus on the assessment and treatment of weight fluctuation and on weight maintenance, irrespective of weight status. © 1995 by John Wiley & Sons, Inc.

BackgroundTo develop a positive aging phenotype, we undertook analyses to describe multiple dimensions of positive aging and their relationships to one another in women 65 years of age and older and evaluate the performance of individual indicators and composite factors of this phenotype as predictors of time to death, years of healthy living, and years of independent living.MethodsData from Women's Health Initiative clinical trial and observational study participants ages 65 years and older at baseline, including follow-up observations up to 8 years later, were analyzed using descriptive statistics and principal components analysis to identify the factor structure of a positive aging phenotype. The factors were used to predict time to death, years of healthy living (without hospitalization or diagnosis of a serious health condition), and years of independent living (without nursing home admission or use of special services).ResultsWe identified a multidimensional phenotype of positive aging that included two factors: Physical-Social Functioning and Emotional Functioning. Both factors were predictive of each of the outcomes, but Physical-Social Functioning was the strongest predictor. Each standard deviation of increase in Physical-Social Functioning was accompanied by a 23.7% reduction in mortality risk, a 19.4% reduction in risk of major health conditions or hospitalizations, and a 26.3% reduction in risk of dependent living.ConclusionsPhysical-Social Functioning and Emotional Functioning constitute important components of a positive aging phenotype. Physical-Social Functioning was the strongest predictor of outcomes related to positive aging, including years of healthy living, years of independent living, and time to mortality.

While observational studies have suggested that vitamin D deficiency increases risk of depression, few clinical trials have tested whether vitamin D supplementation affects the occurrence of depression symptoms. The authors evaluated the impact of daily supplementation with 400 IU of vitamin D(3) combined with 1,000 mg of elemental calcium on measures of depression in a randomized, double-blinded US trial comprising 36,282 postmenopausal women. The Burnam scale and current use of antidepressant medication were used to assess depressive symptoms at randomization (1995-2000). Two years later, women again reported on their antidepressant use, and 2,263 completed a second Burnam scale. After 2 years, women randomized to receive vitamin D and calcium had an odds ratio for experiencing depressive symptoms (Burnam score ≥0.06) of 1.16 (95% confidence interval: 0.86, 1.56) compared with women in the placebo group. Supplementation was not associated with antidepressant use (odds ratio = 1.01, 95% confidence interval: 0.92, 1.12) or continuous depressive symptom score. Results stratified by baseline vitamin D and calcium intake, solar irradiance, and other factors were similar. The findings do not support a relation between supplementation with 400 IU/day of vitamin D(3) along with calcium and depression in older women. Additional trials testing higher doses of vitamin D are needed to determine whether this nutrient may help prevent or treat depression.

There is now growing evidence that the less prevalent allele (A1) of the D2 dopamine receptor (DRD2) gene is strongly associated with severe alcoholism. Similarly, subjects who abuse illegal drugs or who are obese also show a significantly higher prevalence of the A1 DRD2 allele compared to controls. Moreover, cigarette smokers, both past and current, demonstrate significantly higher prevalence of the A1 allele than nonsmokers. In as much as alcohol, cocaine, opiates, nicotine and food are known to increase brain dopamine levels and activate the mesocorticolimbic dopaminergic reward pathways of the brain, it is hypothesized that an inherited deficit of D2 dopamine receptor numbers in brain reward areas of A1 allelic subject predisposes them to substance abuse problems.

Weight dissatisfaction, dieting, and weight change, assessed by questionnaires, were studied in 471 subjects stratified by gender, age (20–60+years) and weight (normal/obese), participating in the RENO Diet Heart Study. Female and obese subjects had more weight dissatisfaction, dieting, and binges and were more overweight in adolescence. Females and

Background: Vitamin D may plausibly reduce the occurrence of depression in postmenopausal women; however, epidemiologic evidence is limited, and few prospective studies have been conducted. Objective: We conducted a cross-sectional and prospective analysis of vitamin D intake from foods and supplements and risk of depressive symptoms. Design: Study participants were 81,189 members of the Women's Health Initiative (WHI) Observational Study who were aged 50–79 y at baseline. Vitamin D intake at baseline was measured by food-frequency and supplement-use questionnaires. Depressive symptoms at baseline and after 3 y were assessed by using the Burnam scale and current antidepressant medication use. Results: After age, physical activity, and other factors were controlled for, women who reported a total intake of ≥800 IU vitamin D/d had a prevalence OR for depressive symptoms of 0.79 (95% CI: 0.71, 0.89; P-trend < 0.001) compared with women who reported a total intake of

In the Women's Health Initiative (WHI) trial of calcium plus vitamin D (CaD), we examined the treatment effect on incidence and mortality for all invasive cancers. Postmenopausal women (N = 36,282) were randomized to 1,000 mg of elemental calcium with 400 IU vitamin D3 or placebo. Cox models estimated risk of cancer incidence and mortality. After 7.0 yr, 1,306 invasive cancers were diagnosed in the supplement and 1,333 in the placebo group [hazard ratio (HR) = 0.98; CI = 0.90, 1.05, unweighted P = 0.54]. Mortality did not differ between supplement (315, annualized% = .26) and placebo [(347, 0.28%; P = 0.17; HR = 0.90 (0.77, 1.05)]. Significant treatment interactions on incident cancer were found for family history of cancer, personal total intake of vitamin D, smoking, and WHI dietary trial randomized group. Calcium/vitamin D supplementation did not reduce invasive cancer incidence or mortality. Supplementation lowered cancer risk in the WHI healthy diet trial arm and in women without a first-degree relative with cancer. The interactions are only suggestive given multiple testing considerations. The low vitamin D dose provided, limited adherence, and lack of serum 25(OH)D values should be considered when interpreting these findings.

Objective.To examine the relationship between arthritis and fracture.Methods.Women were classified into 3 self-reported groups at baseline: no arthritis (n = 83,295), osteoarthritis (OA; n = 63,402), and rheumatoid arthritis (RA; n = 960). Incident fractures were self-reported throughout followup. Age-adjusted fracture rates by arthritis category were generated, and the Cox proportional hazards model was used to test the association between arthritis and fracture.Results.After an average of 7.80 years, 24,137 total fractures were reported including 2559 self-reported clinical spinal fractures and 1698 adjudicated hip fractures. For each fracture type, age-adjusted fracture rates were highest in the RA group and lowest in the nonarthritic group. After adjustment for several covariates, report of arthritis was associated with increased risk for spine, hip, and any clinical fractures. Compared to the nonarthritis group, the risk of sustaining any clinical fracture in the OA group was HR 1.09 (95% CI 1.05, 1.13; p < 0.001) and HR 1.49 (95% CI 1.26, 1.75; p < 0.001) in the RA group. The risk of sustaining a hip fracture was not statistically increased in the OA group (HR 1.11; 95% CI 0.98, 1.25; p = 0.122) compared to the nonarthritis group; however, the risk of hip fracture increased significantly (HR 3.03; 95% CI 2.03, 4.51; p < 0.001) in the RA group compared to the nonarthritis group.Conclusion.The increase in fracture risk confirms the importance of fracture prevention in patients with RA and OA.