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1.
Chronobiol Int ; : 1-12, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31778080

RESUMO

Despite research indicating that sleep disorders influence reproductive health, the effects of sleep on reproductive hormone concentrations are poorly characterized. We prospectively followed 259 regularly menstruating women across one to two menstrual cycles (the BioCycle Study, 2005-2007), measuring fasting serum hormone concentrations up to eight times per cycle. Women provided information about daily sleep in diaries and chronotype and night/shift work on a baseline questionnaire. We evaluated percent differences in mean hormone concentrations, the magnitude of shifts in the timing and amplitude of hormone peaks, and the risk for sporadic anovulation associated with self-reported sleep patterns and night/shift work. We estimated chronotype scores - categorizing women below and above the interquartile range (IQR) as "morning" and "evening" chronotypes, respectively. For every hour increase in daily sleep duration, mean estradiol concentrations increased by 3.9% (95% confidence interval [CI] 2.0, 5.9%) and luteal phase progesterone by 9.4% (CI 4.0, 15.2%). Receiving less than 7 hours of sleep per day was associated with slightly earlier rises in peak levels for several hormones. Women reporting night/shift work (n = 77) had lower testosterone relative to women employed without night/shift work (percent difference: -9.9%, CI -18.4, -0.4%). Women with morning chronotypes (n = 47) had earlier rises in estradiol during their cycles and potentially an earlier rise in luteinizing hormone. Compared to those who had intermediate chronotypes, women with evening chronotypes (n = 42) had a later luteinizing hormone peak of borderline statistical significance. A reduced risk for sporadic anovulation was suggested, but imprecise, for increasing hours of daily sleep leading up to ovulation (risk ratio 0.79, CI 0.59, 1.06), while an imprecise increased risk was observed for women with morning chronotypes (risk ratio 2.50, CI 0.93, 6.77). Sleep-related hormonal changes may not greatly alter ovarian function in healthy women, but have the potential to influence gynecologic health.

2.
BMC Oral Health ; 19(1): 246, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722703

RESUMO

BACKGROUND: The extent to which the composition and diversity of the oral microbiome varies with age is not clearly understood. METHODS: The 16S rRNA gene of subgingival plaque in 1219 women, aged 53-81 years, was sequenced and its taxonomy annotated against the Human Oral Microbiome Database (v.14.5). Composition of the subgingival microbiome was described in terms of centered log(2)-ratio (CLR) transformed OTU values, relative abundance, and prevalence. Correlations between microbiota abundance and age were evelauted using Pearson Product Moment correlations. P-values were corrected for multiple testing using the Bonferroni method. RESULTS: Of the 267 species identified overall, Veillonella dispar was the most abundant bacteria when described by CLR OTU (mean 8.3) or relative abundance (mean 8.9%); whereas Streptococcus oralis, Veillonella dispar and Veillonella parvula were most prevalent (100%, all) when described as being present at any amount. Linear correlations between age and several CLR OTUs (Pearson r = - 0.18 to 0.18), of which 82 (31%) achieved statistical significance (P < 0.05). The correlations lost significance following Bonferroni correction. Twelve species that differed across age groups (each corrected P < 0.05); 5 (42%) were higher in women ages 50-59 compared to ≥70 (corrected P < 0.05), and 7 (48%) were higher in women 70 years and older. CONCLUSIONS: We identified associations between several bacterial species and age across the age range of postmenopausal women studied. Understanding the functions of these bacteria could identify intervention targets to enhance oral health in later life.

3.
Int J Cancer ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31677159

RESUMO

Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type - hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that includes data from 1,167,244 individuals (PLC n=2,208, HCC n=1,154, ICC n=335). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR=1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR=1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5-<25 kg/m2 ; HR=1.14, 95%CI: 1.07-1.21). Hip circumference, per 5 cm increase, was associated with a 9% increased PLC risk (HR=1.09, 95%CI: 1.06-1.12), but no association remained after adjustment for waist circumference (HR=0.99, 95%CI: 0.94-1.03). HCC and ICC results were similar. These findings suggest that excess abdominal size is associated with an increased risk of liver cancer, even among individuals considered to have a normal BMI. However, excess gluteofemoral size alone confers no increased risk. Our findings extend prior analyses, which found an association between excess adiposity and risk of liver cancer, by disentangling the separate effects of excess abdominal and gluteofemoral size through utilization of both waist and hip circumference measurements. This article is protected by copyright. All rights reserved.

4.
J Bone Miner Res ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692127

RESUMO

Short sleep duration, recognized as a public health epidemic, is associated with adverse health conditions, yet little is known about the association between sleep and bone health. We tested the associations of usual sleep behavior and bone mineral density (BMD) and osteoporosis. In a sample of 11,084 postmenopausal women from the Women's Health Initiative (WHI; mean age 63.3 years, SD = 7.4), we performed a cross-sectional study of the association of self-reported usual hours of sleep and sleep quality (WHI Insomnia Rating Score) with whole body, total hip, femoral neck, and spine BMD using linear regression models. We also studied the association of sleep duration and quality with dual-energy X-ray absorptiometry (DXA)-defined low bone mass (T-score < -2.5 to <-1) and osteoporosis (T-score ≤ -2.5) using multinomial regression models. We adjusted for age, DXA machine, race, menopausal symptoms, education, smoking, physical activity, body mass index, alcohol use, physical function, and sleep medication use. In adjusted linear regression models, women who reported sleeping 5 hours or less per night had on average 0.012 to 0.018 g/cm2 significantly lower BMD at all four sites compared with women who reported sleeping 7 hours per night (reference). In adjusted multinomial models, women reporting 5 hours or less per night had higher odds of low bone mass and osteoporosis of the hip (odds ratio [OR] = 1.22; 95% confidence interval [CI] 1.03-1.45, and 1.63; 1.15-2.31, respectively). We observed a similar pattern for spine BMD, where women with 5 hours or less per night had higher odds of osteoporosis (adjusted OR = 1.28; 95% CI 1.02-1.60). Associations of sleep quality and DXA BMD failed to reach statistical significance. Short sleep duration was associated with lower BMD and higher risk of osteoporosis. Longitudinal studies are needed to confirm the cross-sectional effects of sleep duration on bone health and explore associated mechanisms. © 2019 American Society for Bone and Mineral Research.

6.
Int J Cancer ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584193

RESUMO

Breast cancer has been suggested to potentially have prenatal origins. We examined associations between birth weight, body mass index (BMI) at four-time points over 25 years of adulthood, and risk of postmenopausal breast cancer, with emphasis on whether the association between birth weight and risk of breast cancer was mediated by weight and height changes over the adult life course. Postmenopausal women (n = 70,397) aged 50-79 years without breast cancer at enrollment (1993-1998) were followed up to 25 years. Weight and height were measured at baseline. Birth weight, and weights at ages 18, 35 and 50 were self-reported. Breast cancer cases were centrally adjudicated. Compared to women with birth weight of 6-8 pounds, women with birth weight of <6 pounds had lower risk of breast cancer (HR = 0.88 95% CI: 0.79-0.99). 44% and 21% of the relationship between birth weight and breast cancer risk was mediated by adult height and weight at baseline, respectively. Birth weight of 8 pounds or more was not associated with risk of postmenopausal breast cancer. Weight gain in adulthood was associated with increased risk of breast cancer regardless of time periods. In conclusion, lower birthweight was associated with lower risk of postmenopausal breast cancer, and this reduction in risk was significantly mediated by childhood or adolescent growth, especially by adult height. Our data suggest that reaching and maintaining a healthy weight during adulthood is key in the prevention of breast cancer.

7.
JAMA Netw Open ; 2(10): e1914084, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31651972

RESUMO

Importance: Physical activity is inversely associated with hip fracture risk in older women. However, the association of physical activity with fracture at other sites and the role of sedentary behavior remain unclear. Objective: To assess the associations of physical activity and sedentary behavior with fracture incidence among postmenopausal women. Design, Setting, and Participants: The Women's Health Initiative prospective cohort study enrolled 77 206 postmenopausal women aged 50 to 79 years between October 1993 and December 1998 at 40 US clinical centers. Participants were observed for outcomes through September 2015, with data analysis conducted from June 2017 to August 2019. Exposures: Self-reported physical activity and sedentary time. Main Outcomes and Measures: Hazard ratios (HRs) and 95% CIs for total and site-specific fracture incidence. Results: During a mean (SD) follow-up period of 14.0 (5.2) years among 77 206 women (mean [SD] age, 63.4 [7.3] years; 66 072 [85.6%] white), 25 516 (33.1%) reported a first incident fracture. Total physical activity was inversely associated with the multivariable-adjusted risk of hip fracture (>17.7 metabolic equivalent [MET] h/wk vs none: HR, 0.82; 95% CI, 0.72-0.95; P for trend < .001). Inverse associations with hip fracture were also observed for walking (>7.5 MET h/wk vs none: HR, 0.88; 95% CI, 0.78-0.98; P for trend = .01), mild activity (HR, 0.82; 95% CI, 0.73-0.93; P for trend = .003), moderate to vigorous activity (HR, 0.88; 95% CI, 0.81-0.96; P for trend = .002), and yard work (HR, 0.90; 95% CI, 0.82-0.99; P for trend = .04). Total activity was positively associated with knee fracture (>17.7 MET h/wk vs none: HR, 1.26; 95% CI, 1.05-1.50; P for trend = .08). Mild activity was associated with lower risks of clinical vertebral fracture (HR, 0.87; 95% CI, 0.78-0.96; P for trend = .006) and total fractures (HR, 0.91; 95% CI, 0.87-0.94; P for trend < .001). Moderate to vigorous activity was positively associated with wrist or forearm fracture (HR, 1.09; 95% CI, 1.03-1.15; P for trend = .004). After controlling for covariates and total physical activity, sedentary time was positively associated with total fracture risk (>9.5 h/d vs <6.5 h/d: HR, 1.04; 95% CI, 1.01-1.07; P for trend = .01). When analyzed jointly, higher total activity mitigated some of the total fracture risk associated with sedentary behavior. Analysis of time-varying exposures resulted in somewhat stronger associations for total physical activity, whereas those for sedentary time were materially unchanged. Conclusions and Relevance: In older ambulatory women, higher total physical activity was associated with lower total and hip fracture risk but higher knee fracture risk. Mild activity and walking were associated with lower hip fracture risk, a finding with important public health implications because these activities are common in older adults. The positive association between sedentary time and total fracture risk requires further investigation.

8.
Ann Intern Med ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31499528

RESUMO

Background: Whether health outcomes of menopausal estrogen therapy differ between women with and without bilateral salpingo-oophorectomy (BSO) is unknown. Objective: To examine estrogen therapy outcomes by BSO status, with additional stratification by 10-year age groups. Design: Subgroup analyses of the randomized Women's Health Initiative Estrogen-Alone Trial. (ClinicalTrials.gov: NCT00000611). Setting: 40 U.S. clinical centers. Participants: 9939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status. Intervention: Conjugated equine estrogens (CEE) (0.625 mg/d) or placebo for a median of 7.2 years. Measurements: Incidence of coronary heart disease and invasive breast cancer (the trial's 2 primary end points), all-cause mortality, and a "global index" (these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture) during the intervention phase and 18-year cumulative follow-up. Results: The effects of CEE alone did not differ significantly according to BSO status. However, age modified the effect of CEE in women with prior BSO. During the intervention phase, CEE was significantly associated with a net adverse effect (hazard ratio for global index, 1.42 [95% CI, 1.09 to 1.86]) in older women (aged ≥70 years), but the global index was not elevated in younger women (P trend by age = 0.016). During cumulative follow-up, women aged 50 to 59 years with BSO had a treatment-associated reduction in all-cause mortality (hazard ratio, 0.68 [CI, 0.48 to 0.96]), whereas older women with BSO had no reduction (P trend by age = 0.034). There was no significant association between CEE and outcomes among women with conserved ovaries, regardless of age. Limitations: The timing of CEE in relation to BSO varied; several comparisons were made without adjustment for multiple testing. Conclusion: The effects of CEE did not differ by BSO status in the overall cohort, but some findings varied by age. Among women with prior BSO, in those aged 70 years or older, CEE led to adverse effects during the treatment period, whereas women randomly assigned to CEE before age 60 seemed to derive mortality benefit over the long term. Primary Funding Source: The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs.

9.
J Card Fail ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31536806

RESUMO

BACKGROUND: We assessed whether postmenopausal hormone therapy (HT) was associated with incident heart failure (HF) and its subtypes and examined whether there was a modifying effect of age on the associations. METHODS AND RESULTS: Postmenopausal women aged 50-79 enrolled in the Women's Health Initiative HT trials were analyzed. The 16,486 women with a uterus were randomized to receive conjugated equine estrogens (CEE 0.625 mg/day) plus medroxyprogesterone acetate (MPA 2.5 mg/day) or placebo, and 10,739 women with prior hysterectomy were randomized to receive CEE (0.625 mg/day) alone or placebo. Incident HF was defined as the first HF hospitalization. HF with reduced ejection fraction (HFrEF) or preserved EF (HFpEF) was defined as EF < 50% or ≥ 50%. During the intervention phase, median follow-up was 5.6 years in the CEE-plus-MPA trial and 7.2 years in the CEE-alone trial. During the cumulative follow-up of 18.9 years, women randomized to HT vs placebo in the 2 combined trials had incidence rates of 3.90 vs 3.89 per 1000 person-years for total HF; 1.25 vs 1.40 per 1000 person-years for HFrEF, and 1.88 vs 1.79 per 1000 person-years for HFpEF, respectively. There were no significant effects of HT on the risk of total incident HF or its subtypes in either trial, and age at randomization did not significantly modify the results. CONCLUSIONS: Postmenopausal HT did not alter the risk of hospitalization for HF or its subtypes during the intervention or cumulative 18.9 years of follow-up, and results did not vary significantly by age at randomization. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT0000611 https://clinicaltrials.gov/ct2/show/NCT00000611?cond=women%27s±health±initiative&rank=5.

10.
Eur Heart J ; 40(34): 2849-2855, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31256194

RESUMO

AIMS: Central adiposity is associated with increased cardiovascular disease (CVD) risk, even among people with normal body mass index (BMI). We tested the hypothesis that regional body fat deposits (trunk or leg fat) are associated with altered risk of CVD among postmenopausal women with normal BMI. METHODS AND RESULTS: We included 2683 postmenopausal women with normal BMI (18.5 to <25 kg/m2) who participated in the Women's Health Initiative and had no known CVD at baseline. Body composition was determined by dual energy X-ray absorptiometry. Incident CVD events including coronary heart disease and stroke were ascertained through February 2017. During a median 17.9 years of follow-up, 291 incident CVD cases occurred. After adjustment for demographic, lifestyle, and clinical risk factors, neither whole-body fat mass nor fat percentage was associated with CVD risk. Higher percent trunk fat was associated with increased risk of CVD [highest vs. lowest quartile hazard ratio (HR) = 1.91, 95% confidence interval (CI) 1.33-2.74; P-trend <0.001], whereas higher percent leg fat was associated with decreased risk of CVD (highest vs. lowest quartile HR = 0.62, 95% CI 0.43-0.89; P-trend = 0.008). The association for trunk fat was attenuated yet remained significant after further adjustment for waist circumference or waist-to-hip ratio. Higher percent trunk fat combined with lower percent leg fat was associated with particularly high risk of CVD (HR comparing extreme groups = 3.33, 95% CI 1.46-7.62). CONCLUSION: Among postmenopausal women with normal BMI, both elevated trunk fat and reduced leg fat are associated with increased risk of CVD.

11.
Am J Epidemiol ; 188(10): 1838-1848, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31274146

RESUMO

Concerns about reverse causality and selection bias complicate the interpretation of studies of body mass index (BMI, calculated as weight (kg)/height (m)2) and mortality in older adults. The objective of this study was to investigate methodological explanations for the apparent attenuation of obesity-related risks in older adults. We used data from 68,132 participants in the Women's Health Initiative (WHI) clinical trial for this analysis. All of the participants were postmenopausal women aged 50-79 years at baseline (1993-1998). To examine reverse causality and selective attrition, we compared rate ratios from inverse probability of treatment- and censoring-weighted Poisson marginal structural models with results from an unweighted adjusted Poisson regression model. The estimated mortality rate ratios and 95% confidence intervals for BMIs of 30.0-34.9, 35.0-39.9 and ≥40.0 were 0.86 (95% confidence interval (CI): 0.77, 0.96), 0.85 (95% CI: 0.72, 0.99), and 0.88 (95% CI: 0.72, 1.07), respectively, in the unweighted model. The corresponding mortality rate ratios were 0.96 (95% CI: 0.86, 1.07), 1.12 (95% CI: 0.97, 1.29), and 1.31 95% CI: (1.08, 1.57), respectively, in the marginal structural model. Results from the inverse probability of treatment- and censoring-weighted marginal structural model were attenuated in low BMI categories and increased in high BMI categories. The results demonstrate the importance of accounting for reverse causality and selective attrition in studies of older adults.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31326978

RESUMO

BACKGROUND: Hearing loss (HL) and menopausal hormone (conjugated equine estrogens [CEE] and/or medroxyprogesterone acetate [MPA]) are separately associated with cognitive decline and increased risk of incident cognitive impairment. Joint effects of HL and HT could be associated with additive or synergistic decline in global cognition and risk of incident cognitive impairment among postmenopausal women. METHODS: Using the Women's Health Initiative (WHI) Memory Study, 7,220 postmenopausal women with measures of HL, global cognition (Modified Mini- Mental State Examination score), and cognitive impairment (centrally-adjudicated diagnoses of mild cognitive impairment and dementia) from 1996-2009. Multivariable linear mixed effects models were used to analyze rate of change in global cognition. Accelerated failure time models were used to evaluate time to incident cognitive impairment, stratified by HT. RESULTS: Within the CEE-Alone trial, observed adverse effects of CEE-Alone on change in global cognition did not differ by HL, and estimated joint effects of HL and CEE-Alone were not associated with incident cognitive impairment. Within the CEE+MPA trial, HL did not independently accelerate time to cognitive impairment, the adverse effect of CEE+MPA was heightened in older women with HL. Older women on CEE+MPA either with HL (Time Ratio, [TR]=0.82, 95% Confidence Interval, [CI]: 0.71, 0.94) or with normal hearing (TR=0.86, 95% CI: 0.76, 0.97) had faster time to cognitive impairment than those with normal hearing and placebo. CONCLUSIONS: HL may accentuate the adverse effect of CEE+MPA, not CEE-Alone, on global cognitive decline, not incident cognitive impairment, among postmenopausal women on HT.

13.
J Am Geriatr Soc ; 67(9): 1970-1976, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31211407

RESUMO

OBJECTIVES: Selection bias is a well-known concern in research on older adults. We discuss two common forms of selection bias in aging research: (1) survivor bias and (2) bias due to loss to follow-up. Our objective was to review these two forms of selection bias in geriatrics research. In clinical aging research, selection bias is a particular concern because all participants must have survived to old age, and be healthy enough, to take part in a research study in geriatrics. DESIGN: We demonstrate the key issues related to selection bias using three case studies focused on obesity, a common clinical risk factor in older adults. We also created a Selection Bias Toolkit that includes strategies to prevent selection bias when designing a research study in older adults and analytic techniques that can be used to examine, and correct for, the influence of selection bias in geriatrics research. RESULTS: Survivor bias and bias due to loss to follow-up can distort study results in geriatric populations. Key steps to avoid selection bias at the study design stage include creating causal diagrams, minimizing barriers to participation, and measuring variables that predict loss to follow-up. The Selection Bias Toolkit details several analytic strategies available to geriatrics researchers to examine and correct for selection bias (eg, regression modeling and sensitivity analysis). CONCLUSION: The toolkit is designed to provide a broad overview of methods available to examine and correct for selection bias. It is specifically intended for use in the context of aging research. J Am Geriatr Soc 67:1970-1976, 2019.

14.
High Blood Press Cardiovasc Prev ; 26(3): 217-225, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31236901

RESUMO

INTRODUCTION: A possible role of the oral microbiome, specifically oral nitrate reducing flora, in blood pressure (BP) homeostasis, if proven etiologic in nature, could lead to novel mechanism-based therapy to improve hypertension prevention and control. AIM: This cross-sectional study characterized and compared the oral microbiome between four study groups based on BP status among 446 postmenopausal women aged 53-82 years. METHODS: Three study groups were not taking hypertension medication and were separated based on BP, as follows: normal BP (systolic < 120 and diastolic < 80; N = 179), elevated BP/Stage I hypertension (systolic 120-139 or diastolic 80-90; N = 106), Stage II hypertension (systolic > 140 or diastolic > 90; N = 42). The forth group consisted of anyone taking hypertension medications, regardless of BP (N = 119). Subgingival microbiome composition was determined using 16S rRNA sequencing with the Illumina MiSeq platform. Kruskal-Wallis tests were used to compare species-level relative abundance of bacterial operational taxonomic units across the four groups. RESULTS: Sixty-five bacterial species demonstrated significant differences in relative abundance in women with elevated BP or using hypertension medication as compared to those with normal BP. After correction for multiple testing, two species, Prevotella oral (species 317) and Streptococcus oralis, remained significant and were lower in abundance among women taking antihypertension medications compared to those with normal BP (corrected P < 0.05). CONCLUSIONS: These data provide novel description of oral subgingival bacteria grouped according to BP status. Additional larger studies including functional analysis and prospective designs will help further assess the potential role of the oral microbiome in BP regulation and hypertension.


Assuntos
Bactérias/isolamento & purificação , Pressão Sanguínea , Hipertensão/microbiologia , Hipertensão/fisiopatologia , Microbiota , Boca/microbiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Bactérias/classificação , Bactérias/genética , Pressão Sanguínea/efeitos dos fármacos , Estudos Transversais , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Pessoa de Meia-Idade , Pós-Menopausa , Ribotipagem/métodos , Fatores de Risco , Fatores Sexuais
15.
J Natl Cancer Inst ; 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31184362

RESUMO

BACKGROUND: Insulin resistance has been proposed as a mediator of the increased cancer incidence and mortality associated with obesity. However, prior studies included limited cancer deaths and had inconsistent findings. Therefore, we evaluated insulin resistance and cancer-specific and all-cause mortality in postmenopausal women participating in the Women's Health Initiative (WHI). METHODS: Eligible were a subsample of 22 837 WHI participants aged 50-79 years enrolled at 40 US clinical centers from 1993 to 1998 who had baseline fasting glucose and insulin levels. Baseline insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Cancers were verified by central medical record review and deaths verified by medical record and death certificate review enhanced by National Death Index queries. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific and all-cause mortality. All statistical tests were two-sided. RESULTS: During a median of 18.9 years of follow-up, 1820 cancer deaths and 7415 total deaths occurred. Higher HOMA-IR quartile was associated with higher cancer-specific mortality (Q4 vs Q1, HR = 1.26, 95% CI = 1.09 to 1.47; Ptrend = .003) and all-cause mortality (Q4 vs Q1, HR = 1.63, 95% CI = 1.51 to 1.76; Ptrend < .001). A sensitivity analysis for diabetes status did not change findings. Among women with body mass index less than 25 kg/m2, higher HOMA-IR quartile was associated with higher cancer mortality (Fine and Gray, P = .004). CONCLUSIONS: High insulin resistance, as measured by HOMA-IR, identifies postmenopausal women at higher risk for cancer-specific and all-cause mortality who could potentially benefit from early intervention.

16.
Am J Epidemiol ; 188(9): 1616-1626, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31145433

RESUMO

Telomere length is a heritable marker of cellular age that is associated with morbidity and mortality. Poor sleep behaviors, which are also associated with adverse health events, may be related to leukocyte telomere length (LTL). We studied a subpopulation of 3,145 postmenopausal women (1,796 European-American (EA) and 1,349 African-American (AA)) enrolled in the Women's Health Initiative in 1993-1998 with data on Southern blot-measured LTL and self-reported usual sleep duration and sleep disturbance. LTL-sleep associations were analyzed separately for duration and disturbance using weighted and confounder-adjusted linear regression models in the entire sample (AAs + EAs; adjusted for race/ethnicity) and in racial/ethnic strata, since LTL differs by ancestry. After adjustment for covariates, each additional daily hour of sleep beyond 5 hours, approximately, was associated with a 27-base-pair (95% confidence interval (CI): 6, 48) longer LTL in the entire sample. Associations between sleep duration and LTL were strongest among AAs (adjusted ß = 37, 95% CI: 4, 70); a similar, nonsignificant association was observed for EAs (adjusted ß = 20, 95% CI: -7, 48). Sleep disturbance was not associated with LTL in our study. Our models did not show departure from linearity (quadratic sleep terms: P ≥ 0.55). Our results suggest that longer sleep duration is associated with longer LTL in postmenopausal women.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31112615

RESUMO

OBJECTIVES: We examined whether social relationship variables (social support, social strain, social network size, and stressful life events) were associated with risk of developing type 2 diabetes among postmenopausal women. METHOD: 139,924 postmenopausal women aged 50-79 years without prevalent diabetes at baseline were followed for a mean of 14 years. 19,240 women developed diabetes. Multivariable Cox proportional hazard models tested associations between social relationship variables and diabetes incidence after consideration of demographics, depressive symptoms, and lifestyle behaviors. We also examined moderating effects of obesity and race/ethnicity, and we tested whether social variable associations were mediated by lifestyle or depressive symptoms. RESULTS: Compared with the lowest quartile, women in the highest social support quartile had lower risk of diabetes after adjusting for demographic factors, health behaviors, and depressive symptoms (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.89-0.97). Social strain (HR = 1.09, 95% CI = 1.04-1.13) and stressful life events (HR = 1.10, 95% CI = 1.05-1.15) were associated with higher diabetes risks. The association between diabetes and social strain was stronger among African American women. Social relationship variables had direct relationships to diabetes, as well as indirect effects partially mediated by lifestyle and depressive symptoms. DISCUSSION: Social support, social strain, and stressful life events were associated with diabetes risk among postmenopausal women independently of demographic factors and health behaviors. In addition to healthy behaviors such as diet and physical activity, healthy social relationships among older women may be important in the prevention of diabetes.

18.
BMJ Open ; 9(4): e027257, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31023762

RESUMO

OBJECTIVES: Elevated Lipoprotein(a) (Lp[a]) is a well-known risk factor for cardiovascular disease. However, its roles in bone metabolism and fracture risk are unclear. We therefore investigated whether plasma Lp(a) levels were associated with bone mineral density (BMD) and incident hip fractures in a large cohort of postmenopausal women. DESIGN: Post hoc analysis of data from the Women's Health Initiative (WHI), USA. SETTING: 40 clinical centres in the USA. PARTICIPANTS: The current analytical cohort consisted of 9698 white, postmenopausal women enrolled in the WHI, a national prospective study investigating determinants of chronic diseases including heart disease, breast and colorectal cancers and osteoporotic fractures among postmenopausal women. Recruitment for WHI took place from 1 October 1993 to 31 December 1998. EXPOSURES: Plasma Lp(a) levels were measured at baseline. OUTCOME MEASURES: Incident hip fractures were ascertained annually and confirmed by medical records with follow-up through 29 August 2014. BMD at the femoral neck was measured by dual X-ray absorptiometry in a subset of participants at baseline. STATISTICAL ANALYSES: Cox proportional hazards and logistic regression models were used to evaluate associations of quartiles of plasma Lp(a) levels with hip fracture events and hip BMD T-score, respectively. RESULTS: During a mean follow-up of 13.8 years, 454 incident cases of hip fracture were observed. In analyses adjusting for confounding variables including age, body mass index, history of hysterectomy, smoking, physical activity, diabetes mellitus, general health status, cardiovascular disease, use of menopausal hormone therapy, use of bisphosphonates, calcitonin or selective-oestrogen receptor modulators, baseline dietary and supplemental calcium and vitamin D intake and history of fracture, no significant association of plasma Lp(a) levels with low hip BMD T-score or hip fracture risk was detected. CONCLUSIONS: These findings suggest that plasma Lp(a) levels are not related to hip BMD T-score or hip fracture events in postmenopausal women. TRIAL REGISTRATION NUMBER: NCT00000611; Post-results.

19.
Neurology ; 92(18): e2089-e2100, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30926684

RESUMO

OBJECTIVE: To identify prediagnostic plasma metabolomic biomarkers associated with amyotrophic lateral sclerosis (ALS). METHODS: We conducted a global metabolomic study using a nested case-control study design within 5 prospective cohorts and identified 275 individuals who developed ALS during follow-up. We profiled plasma metabolites using liquid chromatography-mass spectrometry and identified 404 known metabolites. We used conditional logistic regression to evaluate the associations between metabolites and ALS risk. Further, we used machine learning analyses to determine whether the prediagnostic metabolomic profile could discriminate ALS cases from controls. RESULTS: A total of 31 out of 404 identified metabolites were associated with ALS risk (p < 0.05). We observed inverse associations (n = 27) with plasma levels of diacylglycerides and triacylglycerides, urate, purine nucleosides, and some organic acids and derivatives, while we found positive associations for a cholesteryl ester, 2 phosphatidylcholines, and a sphingomyelin. The number of significant associations increased to 67 (63 inverse) in analyses restricted to cases with blood samples collected within 5 years of onset. None of these associations remained significant after multiple comparison adjustment. Further, we were not able to reliably distinguish individuals who became cases from controls based on their metabolomic profile using partial least squares discriminant analysis, elastic net regression, random forest, support vector machine, or weighted correlation network analyses. CONCLUSIONS: Although the metabolomic profile in blood samples collected years before ALS diagnosis did not reliably separate presymptomatic ALS cases from controls, our results suggest that ALS is preceded by a broad, but poorly defined, metabolic dysregulation years before the disease onset.

20.
Occup Environ Med ; 76(5): 317-325, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30890565

RESUMO

OBJECTIVES: To assess radiation exposure-related work history and risk of cataract and cataract surgery among radiologic technologists assisting with fluoroscopically guided interventional procedures (FGIP). METHODS: This retrospective study included 35 751 radiologic technologists who reported being cataract-free at baseline (1994-1998) and completed a follow-up questionnaire (2013-2014). Frequencies of assisting with 21 types of FGIP and use of radiation protection equipment during five time periods (before 1970, 1970-1979, 1980-1989, 1990-1999, 2000-2009) were derived from an additional self-administered questionnaire in 2013-2014. Multivariable-adjusted relative risks (RRs) for self-reported cataract diagnosis and cataract surgery were estimated according to FGIP work history. RESULTS: During follow-up, 9372 technologists reported incident physician-diagnosed cataract; 4278 of incident cases reported undergoing cataract surgery. Technologists who ever assisted with FGIP had increased risk for cataract compared with those who never assisted with FGIP (RR: 1.18, 95% CI 1.11 to 1.25). Risk increased with increasing cumulative number of FGIP; the RR for technologists who assisted with >5000 FGIP compared with those who never assisted was 1.38 (95% CI 1.24 to 1.53; p trend <0.001). These associations were more pronounced for FGIP when technologists were located ≤3 feet (≤0.9 m) from the patient compared with >3 feet (>0.9 m) (RRs for >5000 at ≤3 feet vs never FGIP were 1.48, 95% CI 1.27 to 1.74 and 1.15, 95% CI 0.98 to 1.35, respectively; pdifference=0.04). Similar risks, although not statistically significant, were observed for cataract surgery. CONCLUSION: Technologists who reported assisting with FGIP, particularly high-volume FGIP within 3 feet of the patient, had increased risk of incident cataract. Additional investigation should evaluate estimated dose response and medically validated cataract type.

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