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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 < .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.

Background: Advance care planning (ACP) is the process of having conversations with patients to ensure preferences are known and support patient healthcare goals. ACP and the Age‐Friendly Health Systems (AFHS) Initiative's, "What Matters," are synergistic approaches to patient‐centered conversations. Implementation and measurement of ACP in primary care (PC) are variables in quality and consistency. We examined whether participation in an ACP learning collaborative (LC) would improve knowledge and ability to conduct ACP discussions and increase the frequency of documented ACP in participating practices. Methods: The WWAMI (Washington, Wyoming, Alaska, Montana, and Idaho) region Practice and Research Network (WPRN) and the Northwest Geriatrics Workforce Enhancement Center collaboratively organized a 9‐month virtual LC. It consisted of 4 synchronous, 1.5‐h sessions, technical support, and a panel of ACP experts. A Wilcoxon rank sum test assessed differences in knowledge from a pre–post survey. Documentation of ACP in the EHR was collected after at least one plan–do–study–act cycle. Results: We enrolled 17 participants from 6 PC practices (3 hospital‐affiliated; 3 Federally Qualified Health Centers) from the WPRN. Two practices did not complete all LC activities. There was a trend toward increased ACP knowledge and skills overall especially in having discussions patients and families (pre‐mean 2.9 [SD = 0.7]/post‐mean 4.0[SD = 1.1], p < 0.05). 4/6 practices observed an increase in EHR documentation post‐collaborative (median 16.3%, IQR 1.3%–36.9%). Conclusions: The LC increased PC providers knowledge and skills of ACP and AFHS's What Matters, reported ACP EHR documentation, and contributed to practice change. [ABSTRACT FROM AUTHOR]

ObjectivesTo identify potentially modifiable factors associated with overall and poor-quality-of-life (QoL) survival in physically frail older women.DesignProspective study with 7 years of follow-up to examine mortality and, in survivors with a QoL measurement within the next 3 years, to examine poor- versus good-QoL patterns of survival.SettingWomen's Health Initiative Observational Study (WHI OS).ParticipantsFrail older women (N = 11,070; average age 72.6, range 65-82).MeasurementsFrailty was defined using the modified Fried criteria. Study outcomes were overall survival and global QoL. Risk factors were measured at the first follow-up clinic visit for WHI OS participants between 1997 and 2001.ResultsOf 11,070 frail women, 1,487 (13%) died. After 2,677 survivors with poor or unknown QoL were excluded at study baseline, 3,153 (46%) reported good QoL, and 1,263 (18%) reported poor QoL at the end of study follow-up; QoL measures for 2,490 (38%) were unavailable. Older age, history of cardiovascular disease, diabetes mellitus, poor self-rated health, body mass index less than 25.0 kg/m(2) , waist circumference greater than 88 cm, systolic blood pressure greater than 140 mmHg, high number and severity of somatic symptoms, smoking, and low education were associated with greater likelihood of poor-QoL survival. Cumulative baseline risk scores demonstrated an approximately linear increase in probability of poor-QoL survival with an increase in risk factors. The probability of poor-QoL survival was 0.19 (95% confidence interval (CI) = 0.15-0.22) in those with zero to two risk factors and 0.40 (95% CI = 0.35-0.44) in those with six or more risk factors.ConclusionSeveral potentially important risk factors for aging well that can be monitored in clinical and research settings, some of which are modifiable, were identified in a large group of frail old women.

BackgroundAs the proportion of the population aged 80 and over accelerates, so does the value of understanding the processes of aging well. The purposes of this article are to: (a) review contemporary theoretical and conceptual perspectives on aging well, (b) describe indicators of aging well that reflect key concepts and perspectives as assessed in the Women's Health Initiative (WHI) and (c) characterize the status of aging among women aged 80 and older using data obtained from WHI participants at the WHI Extension 2 follow-up.MethodsData from the Lifestyle Questionnaire, which was administered from 2011 to 2012 during the WHI Follow-up Study (Extension 2), were analyzed to provide a profile of the WHI cohort with respect to aging well.ResultsData revealed substantial diversity in the cohort with respect to the various measures of aging well. Although many reported physical functioning levels consistent with disability, most rated their health as good or better. Most reported moderately high levels of resilience, self-control, and self-mastery but lower levels of environmental mastery. Finally, the cohort reported high levels of optimal aging as reflected by their high levels of emotional well-being and moderately high levels of life satisfaction and social support, but more modest levels of personal growth and purpose in life.ConclusionsThe wide range of some dimensions of aging well suggest that further examination of predictors of positive coping and resilience in the face of aging-related disability could identify opportunities to support and facilitate aging well among U.S. women.

Purpose of the studyTrajectories of physical activity (PA) and sedentary time (ST) after military separation are likely important determinants of women's health outcomes later in life, because low PA and high ST are known contributors to premature mortality risk. Our objective was to compare longitudinal trajectories of recreational PA and ST between Veteran and non-Veteran postmenopausal women from the Women's Health Initiative (WHI).Design and methodsWomen Veteran (n = 3,719) and non-Veteran (n = 141,800) WHI participants were included. Self-reported participation in recreational PA, converted to metabolic equivalent (MET)-hours/week, was prospectively assessed over 8 years. Self-reported ST, defined as hours/day sitting or lying down, was collected at baseline and at Years 3 and 6. Generalized estimating equations were used to compare trajectories of PA and ST between Veterans and non-Veterans, adjusted for demographics and lifestyle behaviors.ResultsVeterans had higher baseline PA than non-Veterans (13.2 vs 12.5 MET-hours/week, p = .03). PA declined for both groups, with a steeper decline among Veterans (change/visit year -0.19 vs -0.02 MET-hours/week; interaction p < .001). At baseline, Veterans and non-Veterans had similar levels of ST (107.2 vs 105.9 hours/week, p = 0.42). Over time, ST remained stable among Veterans but declined slightly among non-Veterans (change/visit year -0.19 vs -0.49 hours/week; interaction p = .01).ImplicationsThe less favorable longitudinal trajectories of PA and ST we observed for women Veterans may contribute to worse health among these individuals later in life. Understanding barriers to enhancing PA and reducing ST in women Veterans could lead to more effective approaches to intervening on these health behaviors.

Purpose of the studyA comparison of longitudinal global cognitive functioning in women Veteran and non-Veteran participants in the Women's Health Initiative (WHI).Design and methodsWe studied 7,330 women aged 65-79 at baseline who participated in the WHI Hormone Therapy Trial and its ancillary Memory Study (WHIMS). Global cognitive functioning (Modified Mini-Mental State Examination [3MSE]) in Veterans (n = 279) and non-Veterans (n = 7,051) was compared at baseline and annually for 8 years using generalized linear modeling methods.ResultsCompared with non-Veterans, Veteran women were older, more likely to be Caucasian, unmarried, and had higher rates of educational and occupational attainment. Results of unadjusted baseline analyses suggest 3MSE scores were similar between groups. Longitudinal analyses, adjusted for age, education, ethnicity, and WHI trial assignment revealed differences in the rate of cognitive decline between groups over time, such that scores decreased more in Veterans relative to non-Veterans. This relative difference was more pronounced among Veterans who were older, had higher educational/occupational attainment and greater baseline prevalence of cardiovascular risk factors (e.g., smoking) and cardiovascular disease (e.g., angina, stroke).ImplicationsVeteran status was associated with higher prevalence of protective factors that may have helped initially preserve cognitive functioning. However, findings ultimately revealed more pronounced cognitive decline among Veteran relative to non-Veteran participants, likely suggesting the presence of risks that may impact neuropathology and the effects of which were initially masked by Veterans' greater cognitive reserve.

We examined whether dispositional optimism relates to change in global quality of life (QOL) as a function of either chronological age or years to impending death. We used a sample of 2,096 deceased postmenopausal women from the Women's Health Initiative clinical trials who were enrolled in the 2005-2010 Extension Study and for whom at least 1 global QOL and optimism measure were analyzed. Growth curve models were examined. Competing models were contrasted using model fit criteria. On average, levels of global QOL decreased with both higher age and closer proximity to death (e.g., M(score) = 7.7 eight years prior to death vs. M(score) = 6.1 one year prior to death). A decline in global QOL was better modeled as a function of distance to death (DtD) than as a function of chronological age (Bayesian information criterion [BIC](DtD) = 22,964.8 vs. BIC(age) = 23,322.6). Optimism was a significant correlate of both linear (estimate(DtD) = -0.01, SE(DtD) = 0.005; ρ = 0.004) and quadratic (estimate(DtD) = -0.006, SE(DtD) = 0.002; ρ = 0.004) terminal decline in global QOL so that death-related decline in global QOL was steeper among those with a high level of optimism than those with a low level of optimism. We found that dispositional optimism helps to maintain positive psychological perspective in the face of age-related decline. Optimists maintain higher QOL compared with pessimists when death-related trajectories were considered; however, the gap between those with high optimism and those with low optimism progressively attenuated with closer proximity to death, to the point that is became nonsignificant at the time of death.

BackgroundAspects of eudaimonic well-being, such as personal growth (PG) and purpose in life (PL), have been highlighted as important to older adults' health. We investigated the relationship of PG and PL with patterns of survival to the age of 85 years and older.MethodsThe sample included 8,880 women from the Women's Health Initiative cohort who reached 85 years of age by December 1, 2013, and for whom data on the PG and PL constructs were available. Women were classified into mutually exclusive outcomes: Healthy, Prevalent, Incident, Disabled, and Deceased. PG and PL were each assessed using a modified seven-item measure derived from the Psychological Well-Being scale.ResultsWomen were most commonly classified as Healthy (38.2%, n = 3,395), followed by Incident (24.4%, n = 2,163), Disabled (19.0%, n = 1,685), Prevalent (14.3%, 1,273), and Deceased (4.1%, n = 364). Women with low PL and PG levels were more likely to have prevalent mobility disability and disease or incident death before the age of 85 years. Specifically, those who reported low levels of PG and PL had a 2.1- and 3.6-fold higher risk, respectively, of death.ConclusionsThese findings indicate that even among the oldest old, experience of purposeful life engagement and continuing PG may contribute to better health outcomes.

BackgroundThe purpose of this study was to describe the longitudinal trajectories and bidirectional relationships of the physical-social and emotional functioning (EF) dimensions of positive aging and to identify their baseline characteristics.MethodsWomen age 65 and older who enrolled in one or more Women's Health Initiative clinical trials (WHI CTs) and who had positive aging indicators measured at baseline and years 1, 3, 6, and 9 were included in these analyses (N = 2281). Analytic strategies included latent class growth modeling to identify longitudinal trajectories and multinomial logistic regression to examine the effects of baseline predictors on these trajectories.ResultsA five-trajectory model was chosen to best represent the data. For Physical-Social Functioning (PSF), trajectory groups included Low Maintainer (8.3%), Mid-Low Improver (10.4%), Medium Decliner (10.7%), Mid-High Maintainer (31.2%), and High Maintainer (39.4%); for EF, trajectories included Low Maintainer (3%), Mid-Low Improver (9%), Medium Decliner (7.7%), Mid-High Maintainer (22.8%), and High Maintainer (57.5%). Cross-classification of the groups of trajectories demonstrated that the impact of a high and stable EF on PSF might be greater than the reverse. Low depression symptoms, low pain, and high social support were the most consistent predictors of high EF trajectories.ConclusionAging women are heterogeneous in terms of positive aging indicators for up to 9 years of follow-up. Interventions aimed at promoting sustainable EF might have diffused effects on other domains of healthy aging.

Despite the variety of available analytic methods, longitudinal research in nursing has been dominated by use of a variable-centered analytic approach. The purpose of this article is to present the utility of person-centered methodology using a large cohort of American women 65 and older enrolled in the Women's Health Initiative Clinical Trial (N = 19,891). Four distinct trajectories of energy/fatigue scores were identified. Levels of fatigue were closely linked to age, socio-demographic factors, comorbidities, health behaviors, and poor sleep quality. These findings were consistent regardless of the methodological framework. Finally, we demonstrated that energy/fatigue levels predicted future hospitalization in non-disabled elderly. Person-centered methods provide unique opportunities to explore and statistically model the effects of longitudinal heterogeneity within a population.

Frailty is an emerging geriatric syndrome that refers to a state of increased vulnerability to adverse events including mortality, morbidity, disability, hospitalization, and nursing home admission. Despite its long conceptual and operational history in research and publications, frailty and mechanisms of frailty development are still poorly understood. In this review, we describe a number of conceptual models-reliability, allostatic load, and complexity-that have been put forward to explain the dynamic nature of frailty. We illustrate a consolidated pathophysiological model of frailty, taking into consideration the large and exponentially growing body of studies regarding predictors, indicators, and outcomes of frailty. The model addresses cellular (e.g., oxidative damage and telomere length) and systemic mechanisms (e.g., endocrinal, inflammatory, coagulatory, and metabolic deficiencies) of frailty, moderating or risk factors (e.g., ethnicity, lifestyle, and comorbidities), and outcomes (morbidity, disability, and cognitive decline). Finally, we identify the weaknesses of traditional epidemiological approaches for studying complex phenomena related to frailty and propose areas for future methodological and physiological inquiry.

Frailty is an emerging geriatric syndrome that refers to a state of increased vulnerability to adverse events including mortality, morbidity, disability, hospitalization, and nursing home admission. Despite its long conceptual and operational history in research and publications, frailty and mechanisms of frailty development are still poorly understood. In this review, we describe a number of conceptual models-reliability, allostatic load, and complexity-that have been put forward to explain the dynamic nature of frailty. We illustrate a consolidated pathophysiological model of frailty, taking into consideration the large and exponentially growing body of studies regarding predictors, indicators, and outcomes of frailty. The model addresses cellular (e.g., oxidative damage and telomere length) and systemic mechanisms (e.g., endocrinal, inflammatory, coagulatory, and metabolic deficiencies) of frailty, moderating or risk factors (e.g., ethnicity, lifestyle, and comorbidities), and outcomes (morbidity, disability, and cognitive decline). Finally, we identify the weaknesses of traditional epidemiological approaches for studying complex phenomena related to frailty and propose areas for future methodological and physiological inquiry.

ObjectivesTo examine associations between angiotensin-converting enzyme (ACE) inhibitor and statin medications and baseline and mean annual change in physical performance measures and muscle strength in older women.DesignProspective cohort study.ParticipantsParticipants from the Women's Health Initiative Clinical Trials aged 65 to 79 at baseline who had physical performance measures, self-report of health insurance, and no prior history of stroke or congestive heart failure were included (N = 5,777). Women were recruited between 1993 and 1998.MeasurementsMedication use was ascertained through a baseline inventory. Physical performance measures (timed 6-m walk, repeated chair stands in 15 seconds) and grip strength were assessed at baseline and follow-up Years 1, 3, and 6. Multivariable-adjusted linear repeated-measures models were adjusted for demographic and health characteristics.ResultsACE inhibitor use was associated with lower mean grip strength at baseline (22.40 kg, 95% confidence interval (CI) = 21.89-22.91 vs 23.18 kg, 95% CI 23.02-23.34; P = .005) and greater mean annual change in number of chair stands (-0.182, 95% CI -0.217 to -0.147 vs -0.145, 95% CI -0.156 to -0.133; P = .05) than nonuse. Statin use was not significantly associated with baseline measures or mean annual change for any outcome. A subgroup analysis suggested that statin use was associated with less mean annual change in chair stands (P = .006) in the oldest women.ConclusionThese results do not support an association between statin or ACE inhibitor use and slower decline in physical performance or muscle strength and thus do not support the use of these medications for preserving functional status in older adults.

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.

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.

Abstract Background Observational studies and randomized trials have suggested that estrogens and/or progesterone may lower the risk for colorectal cancer. Inherited variation in the sex-hormone genes may be one mechanism by which sex hormones affect colorectal cancer, although data are limited. Method We conducted a comprehensive evaluation of single nucleotide polymorphisms (SNPs) in genes encoding 3 hormone receptors (ESR1, ESR2, PGR) and 5 hormone synthesizers (CYP19A1 and CYP17A1, HSD17B1, HSD17B2, HSD17B4) among 427 women with incident colorectal cancer and 871 matched controls who were Caucasians of European ancestry from 93676 postmenopausal women enrolled in the Women's Health Initiative Observational cohort. A total of 242 haplotype-tagging and functional SNPs in the 8 genes were included for analysis. Unconditional logistic regression with adjustment for age and hysterectomy status was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results We observed a weak association between the CYP17A1 rs17724534 SNP and colorectal cancer risk (OR per risk allele (A) = 1.39, 95% CI = 1.09-1.78, corrected p-value = 0.07). In addition, a suggestive interaction between rs17724534 and rs10883782 in 2 discrete LD blocks of CYP17A1 was observed in relation to colorectal cancer (empirical p value = 0.04). Moreover, one haplotype block of CYP19A1 was associated with colorectal cancer (corrected global p value = 0.02), which likely reflected the association with the tagging SNP, rs1902584, in the block. Conclusion Our findings offer some support for a suggestive association of CYP17A1 and CYP19A1 variants with colorectal cancer risk.

ObjectivesTo investigate whether midlife and older women who reported prior-year physical abuse, verbal abuse, or both abuse types had higher mortality risk than peers who did not report prior-year abuse.DesignRetrospective analysis.SettingCommunity.ParticipantsOne hundred sixty-thousand six hundred seventy-six community-dwelling women ages 50 to 79 at baseline enrolled in one of two major Women's Health Initiative (WHI) study components who responded to baseline abuse questions. Observational study enrollment was N=93,676 (1994-1998; 90 months average follow-up). Clinical trial enrollment was N=68,132 (1993-1998; 96 months average follow-up).MeasurementsTotal mortality was measured from 1993 to 2005 using all available data sources. Blinded physician adjudicators measured cause-specific mortality. Ninety-six percent of death records were adjudicated.ResultsPrior-year self-reported abuse prevalence was 11.3%. Women who reported physical abuse had the highest age-adjusted mortality rate, followed by women who reported both abuse types. Abuse independently predicted mortality risk after controlling for age, education, ethnicity, and WHI component. High mortality risk remained for physically abused women (hazard ratio (HR)=1.54, 95% confidence interval (CI)=1.09-2.18) after adjusting for demographic and health-related factors. Further adjustment for psychosocial variables diminished this association (HR=1.40, 95% CI=0.93-2.11), but high risk remained.ConclusionCommunity-dwelling middle-aged and older women who reported prior-year physical, verbal, or both types of abuse had significantly higher adjusted mortality risk than women who did not report abuse. These findings highlight the need for longitudinal research into prevention of abuse in later life and accompanying excess mortality and emphasize the importance of abuse prevention in later life.

BackgroundThe immune and blood coagulation systems have been implicated in the pathophysiology of the geriatric syndrome of frailty, but limited prospective data examining the relationship of clotting/inflammation biomarkers to risk of incident frailty exist.MethodsThis prospective analysis was derived from a nested case-control study within the Women's Health Initiative. Among women 65 to 79 years free of frailty at enrollment, we randomly selected 900 incident cases from those developing frailty within 3 years; 900 non-frail controls were individually matched on age, ethnicity, and blood collection date. Biomarkers assessed for risk of incident frailty included fibrinogen, factor VIII, D-dimer, C-reactive protein, interleukin-6, and tissue plasminogen activator (t-PA).ResultsWhen examined by quartiles in multivariable adjusted models, higher D-dimer and t-PA levels were each associated with increased risk of frailty (P trend = .04). Relative to the lowest quartile, the odds ratios for frailty compared with the upper quartile were 1.52 (95% confidence interval, 1.05-2.22) for t-PA and 1.57 (95% confidence interval, 1.11-2.22) for D-dimer. For women having high t-PA and high D-dimer compared with women having lower levels of both biomarkers, the odds of frailty was 2.20 (1.29-3.75). There was little evidence for association between coagulation factor VIII, fibrinogen, C-reactive protein, or interleukin-6 levels and incident frailty.ConclusionThis prospective analysis supports the role of markers of fibrin turnover and fibrinolysis as independent predictors of incident frailty in postmenopausal women.

ObjectivesTo examine the associations between current use, duration, and potency of angiotensin-converting enzyme (ACE) inhibitors and incident frailty in women aged 65 and older who were not frail at baseline.DesignData were from the Women's Health Initiative Observational Study (WHI-OS), a prospective study conducted at 40 U.S. clinical centers.ParticipantsWomen aged 65 to 79 at baseline who were not frail (N=27,378).MeasurementsCurrent ACE inhibitor use was ascertained through direct inspection of medicine containers at baseline. Components of frailty were self-reported low physical function or impaired walking, exhaustion, low physical activity, and unintended weight. Frailty was ascertained through self-reported and physical measurements data at baseline and 3-year clinic contacts.ResultsBy the 3-year follow-up, 3,950 (14.4%) women had developed frailty. Current ACE inhibitor use had no association with incident frailty (multivariate adjusted odds ratio=0.96, 95% confidence interval=0.82-1.13). Duration and potency of ACE inhibitor use were also not significantly associated with incident frailty. A similar pattern of results was observed when incident cardiovascular disease events were studied as a separate outcome or when the sample was restricted to subjects with hypertension.ConclusionOverall, incidence of frailty was similar in current ACE inhibitor users and nonusers.

BackgroundInflammatory biomarkers have shown consistent associations with disability and frailty in older adults. Statin medications may reduce the incidence the frailty because of their anti-inflammatory effects. This study examines associations between current use, duration, and potency of statin medications and incident frailty in initially nonfrail women 65 years old or older.MethodsThe authors conducted a prospective analysis of data from the Women's Health Initiative Observational Study (WHI-OS) conducted at 40 clinical centers in the United States. Eligible women were nonfrail and 65-79 years old at baseline (n = 25,378). Current statin use at baseline was ascertained through direct inspection of medicine containers during clinic visits. Frailty was ascertained through self-reported indicators and physical measurements at baseline and 3-year clinic contacts. Components of frailty included self-reported low physical function, exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models were used to adjust for covariates predicting incident frailty.ResultsAmong the 25,378 eligible women, 3453 (13.6%) developed frailty by the 3-year follow-up contact. Current statin use had no association with incident frailty (multivariate-adjusted odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.85-1.16). Duration and potency of statin use were also not significantly associated with incident frailty. Among low potency statin users, longer duration of use was associated with reduced risk of frailty (p for trend =.02). A similar pattern of results was observed when frailty was studied in the absence of intervening, incident cardiovascular events.ConclusionsOverall, incidence of frailty was similar in current statin users and nonusers.

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.

Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months (1). PDAC has been linked with obesity and glucose intolerance (2-4), but whether changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from individuals with pancreatic cancer (cases) and matched controls from four prospective cohort studies. We find that elevated plasma levels of branched-chain amino acids (BCAAs) are associated with a greater than twofold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years before diagnosis, when occult disease is probably present. We show that plasma BCAAs are also elevated in mice with early-stage pancreatic cancers driven by mutant Kras expression but not in mice with Kras-driven tumors in other tissues, and that breakdown of tissue protein accounts for the increase in plasma BCAAs that accompanies early-stage disease. Together, these findings suggest that increased whole-body protein breakdown is an early event in development of PDAC., PDAC is a leading cause of cancer-related death worldwide, and most patients have incurable disease at diagnosis (1). The best-characterized predisposing factors, current tobacco use and a first-degree relative with [...]

A random clinical study aimed to ascertain the relation between estrogen therapy and calcification in the coronary artery, and the results are documented.

Inhibition of emotional expression has been associated with the incidence and progression of breast cancer and other chronic illnesses. The important health-related factor, however, may be ambivalence about the expression of emotions rather than repression itself. This cross-sectional analysis of baseline data from 159,557 participants in the Women's Health Initiative examined the influence of expression of negative emotion and ambivalence about expression of emotion on psychosocial factors and health-related quality of life measured by the Medical Outcomes Study Short-form 36 (SF-36). Overall, observed correlations were modest but in the expected direction; that is, greater ambivalence about negative emotional expression was associated with worse general health and poorer psychosocial risk profile. Ambivalence about expressing negative emotion was more highly correlated with psychosocial factors and health-related quality of life than emotional expression. In general, our analysis supports prior studies suggesting that ambivalence may be more important to consider in studies of health-related outcomes than expression. KEYWORDS. Cancer-prone personality, expression of emotion, health-related quality of life, psychosocial, personality, women's health

Women's symptoms and management strategies after stopping the intervention in a large estrogen plus progestin trial is described. The results revealed that more than half of the women with vasomotor symptoms at randomization to active medroxyprogesterone acetate (CEE+MPA) reported these symptoms after discontinuing use of the study pills.

The effects of menopausal hormone therapy on the incidence and severity of symptoms of stress, urge, and mixed urinary incontinence (UI) in healthy postmenopausal women are assessed. Conjugated equine estrogen alone and CEE + MPA increased the risk of UI among continent women and worsened the characteristics of UI among symptomatic women after 1 year is concluded.

Inhibition of emotional expression has been associated with the incidence and progression of breast cancer and other chronic illnesses. Others have theorized that it may not be repression itself, but rather ambivalence over the expression of emotions that is the important health-related factor. The Women's Health Initiative (WHI), a 1 ong-term, national study focusing on disease prevention among postmenopausal women, is unique in its assessment of expression and ambivalence of negative emotion in a large study sample of multiethnic, older women. Psychological factors such as expression of negative emotion and ambivalence about expression of emotion are also determined by social patterning. The current study examined the psychometric properties of the instruments used to measure each construct and variation across race/ethnicity and age. The analysis suggests that the scales can be used with confidence in diverse ethnic and age groups. Examining ambivalence about expression of negative emotion in future longitudinal research will further elucidate its role in predicting disease incidence and recovery, both important in reducing the public health burden of chronic disease. KEYWORDS. Expression of negative emotion, ambivalence over the expression of emotions, cancer prone personality, race/ethnicity, postmenopausal women