Social isolation and incident heart failure hospitalization in older women: Women\u27s health initiative study findings

Background The association of social isolation or lack of social network ties in older adults is unknown. This knowledge gap is important since the risk of heart failure (HF) and social isolation increase with age. The study examines whether social isolation is associated with incident HF in older women, and examines depressive symptoms as a potential mediator and age and race and ethnicity as effect modifiers. Methods and Results This study included 44 174 postmenopausal women of diverse race and ethnicity from the WHI (Women\u27s Health Initiative) study who underwent annual assessment for HF adjudication from baseline enrollment (1993-1998) through 2018. We conducted a mediation analysis to examine depressive symptoms as a potential mediator and further examined effect modification by age and race and ethnicity. Incident HF requiring hospitalization was the main outcome. Social isolation was a composite variable based on marital/partner status, religious ties, and community ties. Depressive symptoms were assessed using CES-D (Center for Epidemiology Studies-Depression). Over a median follow-up of 15.0 years, we analyzed data from 36 457 women, and 2364 (6.5%) incident HF cases occurred; 2510 (6.9%) participants were socially isolated. In multivariable analyses adjusted for sociodemographic, behavioral, clinical, and general health/functioning; socially isolated women had a higher risk of incident HF than nonisolated women (HR, 1.23; 95% CI, 1.08-1.41). Adding depressive symptoms in the model did not change this association (HR, 1.22; 95% CI, 1.07-1.40). Neither race and ethnicity nor age moderated the association between social isolation and incident HF. Conclusions Socially isolated older women are at increased risk for developing HF, independent of traditional HF risk factors. Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT00000611

HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.

BACKGROUND: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. METHODS: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. FINDINGS: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials). INTERPRETATION: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. FUNDING: The funding sources are cited at the end of the paper

Parental longevity predicts healthy ageing among women.

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 <70, 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

Associations of parental ages at childbirth with healthy aging among women

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 <25, 25-29, 30-34, or ≥35 years. RESULTS:Women were aged on average 71.3 (standard deviation 2.7; range 65-79) years at baseline. There was no significant association of maternal age at childbirth with healthy survival to age 90 or death before age 90. Women born to fathers aged ≥35 compared with 30-34 years at their births were more likely to achieve healthy than usual survival (OR, 1.15; 95% CI, 1.00-1.32). There was no association of paternal age at childbirth with death before age 90. CONCLUSIONS:Findings suggest that being born to older fathers was associated with healthy survival to age 90 among women who had survived to ages 65-79 years at study baseline. There was no association of maternal age at childbirth with healthy survival to age 90 among these older women

Parental longevity predicts healthy ageing among women.

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 <70, 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

Effects of estrogen plus progestin on health-related quality of life

BACKGROUND: The Women\u27s Health Initiative (WHI) and other clinical trials indicate that significant health risks are associated with combination hormone use. Less is known about the effect of hormone therapy on health-related quality of life. METHODS: The WHI randomly assigned 16,608 postmenopausal women 50 to 79 years of age (mean, 63) with an intact uterus at base line to estrogen plus progestin (0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate, in 8506 women) or placebo (in 8102 women). Quality-of-life measures were collected at base line and at one year in all women and at three years in a subgroup of 1511 women. RESULTS: Randomization to estrogen plus progestin resulted in no significant effects on general health, vitality, mental health, depressive symptoms, or sexual satisfaction. The use of estrogen plus progestin was associated with a statistically significant but small and not clinically meaningful benefit in terms of sleep disturbance, physical functioning, and bodily pain after one year (the mean benefit in terms of sleep disturbance was 0.4 point on a 20-point scale, in terms of physical functioning 0.8 point on a 100-point scale, and in terms of pain 1.9 points on a 100-point scale). At three years, there were no significant benefits in terms of any quality-of-life outcomes. Among women 50 to 54 years of age with moderate-to-severe vasomotor symptoms at base line, estrogen and progestin improved vasomotor symptoms and resulted in a small benefit in terms of sleep disturbance but no benefit in terms of the other quality-of-life outcomes. CONCLUSIONS: In this trial in postmenopausal women, estrogen plus progestin did not have a clinically meaningful effect on health-related quality of life

Vitamin D Supplementation and Depression in the Women\u27s Health Initiative Calcium and Vitamin D Trial

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

Estrogen-Plus-Progestin Use and Mammographic Density in Postmenopausal Women: Women's Health Initiative Randomized Trial

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

Toward a positive aging phenotype for older women: observations from the women's health initiative.

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

Toward a positive aging phenotype for older women: observations from the women's health initiative.

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