Blood-based biomarkers for Alzheimer's disease and cognitive function from mid- to late life.

INTRODUCTION: We investigated associations of Alzheimer's disease (AD) serum biomarkers with longitudinal changes in cognitive function from mid- to late life among women. METHODS: The study population included 192 women with the median age of 53.3 years at baseline, from the Study of Women's Health Across the Nation Michigan Cohort, followed up over 14 years. Associations between baseline serum amyloid ß (Aß)42, the Aß42/40 ratio, phosphorylated tau181 (p-tau181), and total tau with longitudinal changes in cognition were evaluated using linear mixed effects models. RESULTS: After adjusting for confounders, lower Aß42/40 ratios were associated with faster declines in the Digit Span Backward Test. Higher p-tau181 also showed a borderline statistically significant association with more rapid decline in the Symbol Digit Modalities Test. DISCUSSION: Our findings suggest that mid-life serum AD biomarkers could be associated with accelerated cognitive decline from mid- to late life in women. Future studies with larger samples are needed to validate and extend our findings. HIGHLIGHTS: This study investigates midlife serum AD biomarkers on longitudinal cognitive function changes in women. Mid-life serum AD biomarkers are associated with accelerated cognitive decline. A decrease in the Aß42/40 ratio was associated with a faster decline in the DSB score. A higher p-tau181 concentration was associated with a faster decline in the SDMT score.

Isomer-Specific Serum Concentrations of Perfluorooctane Sulfonic Acid among U.S. Adults: Results from the National Health and Nutrition Examination Survey (NHANES) and the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS).

Electrochemical fluorination manufacture of perfluorooctane sulfonic acid (PFOS), one of the most studied per- and polyfluoroalkyl substances, produces mixtures of linear and branched isomers, but little is known about human exposure to linear or branched PFOS isomers. We examined determinants affecting isomer-specific patterns of PFOS in serum in two adult populations in the United States, the National Health and Nutrition Examination Survey (NHANES) and the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS). After adjusting for demographic variables, fish consumption (in both populations), a glomerular filtration rate above 90 mL/min/1.73 m2 (observed in NHANES; not tested in SWAN-MPS), premenopausal status (only observed in SWAN-MPS), and less consumption of processed food (observed in SWAN-MPS; not tested in NHANES) were associated with a higher proportion of linear PFOS. Non-Hispanic Black and Asian participants were likely to have a higher proportion of linear PFOS than non-Hispanic White participants in both populations. Our findings suggest that isomer-specific patterns of PFOS serum concentrations in humans vary depending on population characteristics that affect PFOS exposure and excretion. Consideration of specific PFOS isomers in future human biomonitoring and epidemiologic studies can provide useful insight to better understand PFOS exposure.

Cardiometabolic disease and obesity patterns differentially predict acute kidney injury after total joint replacement: a retrospective analysis.

BACKGROUND: Acute kidney injury (AKI) is a frequent yet understudied postoperative total joint arthroplasty complication. This study aimed to describe cardiometabolic disease co-occurrence using latent class analysis, and associated postoperative AKI risk. METHODS: This retrospective analysis examined patients ≥18 years old undergoing primary total knee or hip arthroplasties within the US Multicenter Perioperative Outcomes Group of hospitals from 2008 to 2019. AKI was defined using modified Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Latent classes were constructed from eight cardiometabolic diseases including hypertension, diabetes, and coronary artery disease, excluding obesity. A mixed-effects logistic regression model was constructed for the outcome of any AKI and the exposure of interaction between latent class and obesity status adjusting for preoperative and intraoperative covariates. RESULTS: Of 81 639 cases, 4007 (4.9%) developed AKI. Patients with AKI were more commonly older and non-Hispanic Black, with more significant comorbidity. A latent class model selected three groups of cardiometabolic patterning, labelled 'hypertension only' (n=37 223), 'metabolic syndrome (MetS)' (n=36 503), and 'MetS+cardiovascular disease (CVD)' (n=7913). After adjustment, latent class/obesity interaction groups had differential risk of AKI compared with those in 'hypertension only'/non-obese. Those 'hypertension only'/obese had 1.7-fold increased odds of AKI (95% confidence interval [CI]: 1.5-2.0). Compared with 'hypertension only'/non-obese, those 'MetS+CVD'/obese had the highest odds of AKI (odds ratio 3.1, 95% CI: 2.6-3.7), whereas 'MetS+CVD'/non-obese had 2.2 times the odds of AKI (95% CI: 1.8-2.7; model area under the curve 0.76). CONCLUSIONS: The risk of postoperative AKI varies widely between patients. The current study suggests that the co-occurrence of metabolic conditions (diabetes mellitus, hypertension), with or without obesity, is a more important risk factor for acute kidney injury than individual comorbid diseases.

Phthalate exposure is associated with more rapid body fat gain in midlife women: The Study of Women's Health Across the Nation (SWAN) Multi-Pollutant Study.

Obesity is a major threat to health, but the etiology of obesity is incompletely understood. Phthalates, synthetic chemicals ubiquitous in the environment, are suspected to have obesogenic effects, but the relationship of phthalates and obesity in humans remains uncertain. We examined whether phthalate exposure was associated with body fat gain in midlife women. We analyzed data from 1369 women in the Study of Women's Health Across the Nation Multi-Pollutant Study. Eleven phthalate metabolites measured in spot urine samples at baseline (1999/2000) were standardized with covariate-adjusted creatinine. Body weight (BW), fat mass (FM) from dual-energy X-ray absorptiometry (DXA), and body fat percentage (BF%) from DXA were measured near-annually until 2016/2017. For each metabolite, linear mixed effects models with time and log2(metabolite) interactions were examined, adjusting for demographic, lifestyle, and menopause-related factors. Analyses were conducted overall and stratified by baseline obesity status. As sensitivity analyses, all analyses were repeated using a second set of metabolites measured in 2002/2003. Higher levels of all metabolites except mono-carboxy-isononyl phthalate were associated with faster increases in BF%. Per doubling of metabolite concentrations, differences in five-year BF% change ranged from 0.03 percentage point (ppt) (95% confidence interval (CI): -0.03, 0.09) for mono-isobutyl phthalate to 0.09 ppt (95% CI: 0.02, 0.16) for mono(3-carboxypropyl) phthalate. Results were similar for FM change, but associations with BW change were mostly null. In stratified analyses by baseline obesity status, positive associations were strongest in women who were normal/underweight at baseline. When metabolites from 2002/2003 were used as exposures, most associations were attenuated and not statistically significant, but they remained positive for normal/underweight women. In conclusion, phthalate metabolites were associated with more rapid body fat gain in midlife women, but our results need confirmation given attenuation of estimates in the sensitivity analyses.

The role of exposure to per- and polyfluoroalkyl substances in racial/ethnic disparities in hypertension: Results from the study of Women's health across the nation.

BACKGROUND: Racial/ethnic disparities in hypertension are a pressing public health problem. The contribution of environmental pollutants including PFAS have not been explored, even though certain PFAS are higher in Black population and have been associated with hypertension. OBJECTIVES: We examined the extent to which racial/ethnic disparities in incident hypertension are explained by racial/ethnic differences in serum PFAS concentrations. METHODS: We included 1058 hypertension-free midlife women with serum PFAS concentrations in 1999-2000 from the multi-racial/ethnic Study of Women's Health Across the Nation with approximately annual follow-up visits through 2017. Causal mediation analysis was conducted using accelerated failure time models. Quantile-based g-computation was used to evaluate the joint effects of PFAS mixtures. RESULTS: During 11,722 person-years of follow-up, 470 participants developed incident hypertension (40.1 cases per 1000 person-years). Black participants had higher risks of developing hypertension (relative survival: 0.58, 95% CI: 0.45-0.76) compared with White participants, which suggests racial/ethnic disparities in the timing of hypertension onset. The percent of this difference in timing that was mediated by PFAS was 8.2% (95% CI: 0.7-15.3) for PFOS, 6.9% (95% CI: 0.2-13.8) for EtFOSAA, 12.7% (95% CI: 1.4-22.6) for MeFOSAA, and 19.1% (95% CI: 4.2, 29.0) for PFAS mixtures. The percentage of the disparities in hypertension between Black versus White women that could have been eliminated if everyone's PFAS concentrations were dropped to the 10th percentiles observed in this population was 10.2% (95% CI: 0.9-18.6) for PFOS, 7.5% (95% CI: 0.2-14.9) for EtFOSAA, and 17.5% (95% CI: 2.1-29.8) for MeFOSAA. CONCLUSIONS: These findings suggest differences in PFAS exposure may be an unrecognized modifiable risk factor that partially accounts for racial/ethnic disparities in timing of hypertension onset among midlife women. The study calls for public policies aimed at reducing PFAS exposures that could contribute to reductions in racial/ethnic disparities in hypertension.

Identifying latent classes of Relative Energy Deficiency in Sport (RED-S) consequences in a sample of collegiate female cross country runners.

OBJECTIVE: The purpose of this study was to identify patterns of clustering of the 10 health consequences identified in the Relative Energy Deficiency in Sport (RED-S) framework among collegiate female Cross-Country runners. We also assessed risk characteristics associated with each cluster. METHODS: This randomly sampled population included 211 current National Collegiate Athletics Association (NCAA) Division I (DI) female cross country runners who completed a quantitative survey. We used latent class analysis (LCA) to group athletes into mutually exclusive classes based on shared response patterns of RED-S consequences. We computed descriptive statistics to identify demographics, personal characteristics, disordered eating and emotional health characteristics associated with each class. RESULTS: The average age of the sample was 21 years with mean body mass index 20.4 kg/m2. The LCA identified three unique classes of potential RED-S presentations: (1) low probability of RED-S consequences; (2) complex physical and psychological concerns with a higher burden of cardiovascular concern and (3) very high probability of anxiety with high burden of menstrual disturbance, bone injury and gastrointestinal concern. All classes were characterised by high levels of menstrual disturbance and distinguished by the number and burden of other potential RED-S consequences and in reported abuse history, emotional regulation and perfectionism. CONCLUSION: This study identified a high burden of menstrual disturbance in NCAA D1 cross country runners, and three unique presentations of RED-S consequences. Future research is warranted to better understand how early prevention and intervention strategies may mitigate RED-S consequences in distance runners.

Per- and polyfluoroalkyl substances and incident diabetes in midlife women: the Study of Women's Health Across the Nation (SWAN).

AIMS/HYPOTHESIS: Diabetogenic effects of per- and polyfluoroalkyl substances (PFAS) have been suggested. However, evidence based on prospective cohort studies is limited. We examined the association between serum PFAS concentrations and incident diabetes in the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS). METHODS: We included 1237 diabetes-free women aged 45-56 years at baseline (1999-2000) who were followed up to 2017. At each follow-up visit, women with incident diabetes were identified by the presence of one or more of the following conditions: (1) use of a glucose-lowering medication at any visit; (2) fasting glucose ≥7 mmol/l on two consecutive visits while not on steroids; and (3) any two visits with self-reported diabetes and at least one visit with fasting blood glucose ≥7 mmol/l. Serum concentrations of 11 PFAS were quantified by online solid-phase extraction-HPLC-isotope dilution-tandem MS. Seven PFAS with high detection rates (>96%) (n-perfluorooctanoic acid [n-PFOA], perfluorononanoic acid [PFNA], perfluorohexane sulfonic acid [PFHxS], n-perfluorooctane sulfonic acid [n-PFOS], sum of perfluoromethylheptane sulfonic acid isomers [Sm-PFOS], 2-[N-methyl-perfluorooctane sulfonamido] acetic acid [MeFOSAA] and 2-[N-ethyl-perfluorooctane sulfonamido] acetic acid) were included in data analysis. Cox proportional hazards models were used to compute HRs and 95% CIs. Quantile-based g-computation was used to evaluate the joint effects of PFAS mixtures. RESULTS: After adjustment for race/ethnicity, site, education, smoking status, alcohol consumption, total energy intake, physical activity, menopausal status and BMI, the HR (95% CI) comparing the lowest with the highest tertile was 1.67 (1.21, 2.31) for n-PFOA (ptrend = 0.001), 1.58 (1.13, 2.21) for PFHxS (ptrend = 0.003), 1.36 (0.97, 1.90) for Sm-PFOS (ptrend = 0.05), 1.85 (1.28, 2.67) for MeFOSAA (ptrend = 0.0004) and 1.64 (1.17, 2.31) for the sum of four common PFAS (n-PFOA, PFNA, PFHxS and total PFOS) (ptrend = 0.002). Exposure to seven PFAS as mixtures was associated with an HR of 2.62 (95% CI 1.12, 6.20), comparing the top with the bottom tertiles for all seven PFAS. CONCLUSIONS/INTERPRETATION: This study suggests that PFAS may increase diabetes risk in midlife women. Reduced exposure to these 'forever and everywhere chemicals' may be an important preventative approach to lowering population-wide diabetes risk.

Metals and risk of incident metabolic syndrome in a prospective cohort of midlife women in the United States.

Exposure to metals may contribute to the development of metabolic syndrome (MetS); however, evidence from midlife women who are at greater risk of cardiometabolic disease is limited. We assessed the associations of 15 urinary metal concentrations with incident MetS in a prospective cohort of midlife women in the United States. The study population included 947 White, Black, Chinese and Japanese women, aged 45-56 years, free of MetS at baseline (1999-2000), who participated in the Study of Women's Health Across the Nation Multi-Pollutant Study. Fifteen metals were detected in almost all participants urine samples using inductively coupled plasma mass spectrometry at the baseline. Incident MetS was identified annually through 2017 as having at least three of the following five components: high blood pressure, impaired fasting glucose, abdominal obesity, high triglycerides, and poor high-density lipoprotein cholesterol. We used the Cox proportional hazards models to investigate the associations between individual metals and MetS incidence. The adjusted hazard ratios (HR) (95% CI) for MetS in associations with each doubling of urinary metal concentration were 1.14 (1.08, 1.23) for arsenic, 1.14 (1.01, 1.29) for cobalt, and 1.20 (1.06, 1.37) for zinc. We further evaluated the associations between metal mixtures and MetS using the elastic net penalized Cox model and summarized the results into the environmental risk score (ERS). Arsenic, barium, cobalt, copper, nickel, antimony, thallium, and zinc had positive weights, and cadmium, cesium, mercury, molybdenum, lead, and tin had negative weights in the construction of the ERS. The adjusted HR of MetS comparing 75th vs. 25th percentiles of the ERS was 1.45 (1.13, 1.87). These findings support the view that arsenic, cobalt, zinc, as well as metal mixtures, might influence the risks of incident MetS in midlife women.

Perfluoroalkyl and polyfluoroalkyl substances and body size and composition trajectories in midlife women: the study of women's health across the nation 1999-2018.

BACKGROUND/OBJECTIVES: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been suggested as obesogens but epidemiologic evidence is limited. We examined associations of serum PFAS concentrations with longitudinal trajectories of weight, waist circumference (WC), fat mass, and proportion fat in midlife women. SUBJECTS/METHODS: This study included 1,381 midlife women, with a total of 15,000 repeated measures from the multi-racial/ethnic Study of Women's Health Across the Nation between 1999 and 2018. The average follow-up was 14.9 (range: 0-18.6) years. Body size (objectively measured weight and WC) and body composition from dual-energy X-ray absorptiometry were assessed at near-annual visits. Linear mixed models with piecewise linear splines were utilized to model non-linear trajectories of body size and composition. RESULTS: After multivariable adjustment, PFAS concentrations were positively associated with weight, WC, fat mass, and proportion fat at baseline and during follow-up. Comparing the highest to the lowest tertiles of PFAS concentrations, adjusted geometric mean weight was 73.9 kg vs. 69.6 kg for PFOS (P < 0.0001), and 74.0 vs. 69.4 kg for linear PFOA (P < 0.0001) at baseline. Women with the highest tertile of PFOS had an annual increase rate of 0.33% (95% CI: 0.27%, 0.40%) in weight, compared to the lowest tertile with 0.10% (95% CI: 0.04%, 0.17%) (P < 0.0001). PFOS was also significantly related to higher increase rates in WC (difference = 0.12% per year, P = 0.002) and fat mass (difference = 0.25% per year, P = 0.0002). EtFOSAA and MeFOSAA showed similar effects to PFOS. Although PFHxS was not related to body size or fat at baseline, PFHxS was significantly associated with accelerated increases in weight (P < 0.0001), WC (P = 0.003), fat mass (P < 0.0001), and proportion fat (P = 0.0009). No significant results were found for PFNA. CONCLUSIONS: Certain PFAS were positively associated with greater body size and body fat, and higher rates of change over time. PFAS may be an underappreciated contributing factor to obesity risk.

Paper towel test as independently self-administered to quantify cough-related urine loss: Compliance and comparisons with survey-only data in SWAN.

AIMS: The epidemiologic Study of Women's Health Across the Nation (SWAN) includes urinary incontinence (UI) questionnaire items. We introduced an independently self-administered paper towel test (PTT-ISA; invention disclosure #2021-347) to objectively demonstrate UI. Aims were to determine: (1) PTT-ISA compliance and (2) relationship to questionnaire results. METHODS: 276 community women were invited to complete both SWAN questionnaire and PTT-ISA. For PTT-ISA, a woman holds a trifold brown paper towel against her perineum while coughing hard three times. She checks the towel for wetness and compares it with pictorial showing wetted area gradations (dry towel through >6 ml/saturated). She then selects the best photo match for her towel. A newly conceptualized variable constructed as PTT-ISA plus questionnaire results was formed. RESULTS: Of 276 women, noncompliance with PTT-ISA was 2.2% (6 women). Four others (1.5%) were missing questionnaires. For the remaining 266 women, conceptual cohesiveness between questionnaire-only and PTT-ISA + questionnaire was demonstrated in 165 (62.0%). Lack of cohesiveness occurred in 101 (38.9%), including 41 women who said "no" to the questionnaire item indicative of stress UI and had leakage on PTT-ISA; leakage degree varied across the full pictorial spectrum from drops to saturated. CONCLUSION: PTT-ISA demonstrates high compliance, with rate comparable to survey compliance. It is a novel measure for objective sign of urine loss when independently self-administered by community women outside of a clinic environment. Further research comparing PTT-ISA with clinician-observed cough test is warranted. As independently self-administered, PTT-ISA is simple, noninvasive, inexpensive, and an acceptable test that adds value to otherwise survey-dependent research.

Urinary metals and adipokines in midlife women: The Study of Women's Health Across the nation (SWAN).

BACKGROUND: Information on the associations between metal exposures and adipokines in human populations is limited and results are inconsistent. We evaluated the associations between metals and adipokines. METHODS: Urinary concentrations of 15 metals (arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc) were measured in 1999-2000 among 1228 women of the Study of Women's Health Across the Nation Multi-Pollutant Study. Serum adipokines including high molecular weight (HMW)-adiponectin, leptin, and soluble leptin receptor (sOB-R) were measured at the follow-up visit (2002-2003). Linear regression models with adaptive elastic-net (AENET) were fit to identify metals associated with adipokines and to compute estimated percent changes in adipokines for one standard deviation increase in log-transformed urinary metal concentrations. RESULTS: After adjustment for confounders, urinary molybdenum was associated with a 5.54% higher level (95% CI: 1.36%, 9.90%), whereas cadmium was associated with a 4.53% lower level (95% CI: -8.17%, -0.76%) of HMW-adiponectin. Urinary molybdenum was also associated with a 5.95% lower leptin level (95% CI: -10.15%, -1.56%) and a 2.98% (95% CI: 0.69%, 5.32%) higher sOB-R level. Urinary cesium and lead were associated with a 3.58% (95% CI: -6.06%, -1.03%) and a 2.53% (95% CI: -4.80%, -0.21%) lower level of sOB-R, respectively. CONCLUSIONS: Our findings suggest that molybdenum was associated with favorable profiles of HMW-adiponectin, leptin, and sOB-R. Exposures to cadmium, cesium, and lead were associated with adverse adipokine profiles.

Cultural and environmental associations with body image, diet and well-being in NCAA DI female distance runners: a qualitative analysis.

OBJECTIVE: We aimed to describe current and former National Collegiate Athletic Association (NCAA) Division One (DI) female distance runners' experiences of perceived norms of body image and disordered eating in their sport, as well as the emergence and influence of coach-athlete power dynamics.This manuscript reports a qualitative research study (consisting of interviews and thematic analysis) of women athletes' experiences of perceived norms of body image and disordered eating in their sport. We also report athletes' experiences of coach-athlete power dynamics. METHODS: The study sample included 29 current and former female NCAA DI female distance runners, defined as competing in 800-metre distance or greater. Interviews were conducted, audio-recorded and hand transcribed. A thematic analysis was performed and presented. RESULTS: Two major themes emerged: (1) sport body ideals and body image norms and myths that exist in the sport, and (2) the power dynamic between athletes and coaches. It is not clear whether sport body ideals and culture of running influences coaching culture, or whether the coaches-who maintain positions of power in the sport-perpetuate the culture. These themes likely feed into each other and reinforce the existing and dominant mentalities of the sport. CONCLUSION: Sport body image ideals and the power dynamic between coach and athlete may contribute to female athlete's risk of disordered eating and body image disturbance. We call for the NCAA and athletic departments to develop and implement prevention and intervention programmes to prevent eating and body image disorders in this high-risk population.

Western Dietary Pattern Derived by Multiple Statistical Methods Is Prospectively Associated with Subclinical Carotid Atherosclerosis in Midlife Women.

BACKGROUND: The menopause has adverse effects on cardiometabolic profiles that are linked to an increased risk of atherosclerosis in women. A healthy diet during the menopausal transition may counteract the menopause-induced atherosclerotic risk. OBJECTIVE: This prospective cohort study aimed to examine the associations between empirically derived dietary patterns and subclinical carotid atherosclerosis in midlife women. METHODS: A total of 1246 midlife women (average age at baseline: 46.3 y) from the Study of Women's Health Across the Nation who completed dietary assessments and had a carotid ultrasound scan were included. Dietary data were collected at 3 time points, during 1996-1997, 2001-2003, and 2005-2007. Measures of carotid atherosclerosis included common carotid artery intima-media thickness (CCA-IMT), adventitial diameter (AD), and carotid plaque index collected during 2009-2013. Three statistical methods, including principal component analysis (PCA), reduced rank regression (RRR), and partial least squares regression (PLS), were used to identify dietary patterns. RESULTS: A Western dietary pattern was identified from each method and a Prudent dietary pattern from PCA. High adherence to the Western pattern was associated with higher CCA-IMT. Women in the fourth quartile of the Western pattern identified by PCA, RRR, and PLS had 0.042 mm (95% CI: 0.011, 0.073), 0.033 mm (95% CI: 0.0086, 0.057), and 0.049 mm (95% CI: 0.025, 0.074), respectively, larger CCA-IMT than women in the first quartile; these differences correspond to 30%, 24%, and 35% of the sample SD, respectively. The Prudent pattern was not significantly associated with CCA-IMT. No significant associations were found between the identified dietary patterns and AD or carotid plaque. CONCLUSIONS: The positive association between the Western diet and CCA-IMT was robust under different dietary pattern derivation methods. The adoption of a diet low in red meat, processed meat, deep-fried products, and sugar-sweetened beverages among midlife women is associated with a lower future risk of atherosclerosis.

Body mass index versus bioelectrical impedance analysis for classifying physical function impairment in a racially diverse cohort of midlife women: the Study of Women's Health Across the Nation (SWAN).

BACKGROUND: Body composition strongly influences physical function in older adults. Bioelectrical impedance analysis (BIA) differentiates fat mass from skeletal muscle mass, and may be more useful than body mass index (BMI) for classifying women on their likelihood of physical function impairment. AIMS: This study tested whether BIA-derived estimates of percentage body fat (%BF) and height-normalized skeletal muscle mass (skeletal muscle mass index; SMI) enhance classification of physical function impairment relative to BMI. METHOD: Black, White, Chinese, and Japanese midlife women (N = 1482) in the Study of Women's Health Across the Nation (SWAN) completed performance-based measures of physical function. BMI (kg/m2) was calculated. %BF and SMI were derived through BIA. Receiver-operating characteristic (ROC) curve analysis, conducted in the overall sample and stratified by racial group, evaluated optimal cutpoints of BMI, %BF, and SMI for classifying women on moderate-severe physical function impairment. RESULTS: In the overall sample, a BMI cutpoint of ≥ 30.1 kg/m2 correctly classified 71.1% of women on physical function impairment, and optimal cutpoints for %BF (≥ 43.4%) and SMI (≥ 8.1 kg/m2) correctly classified 69% and 62% of women, respectively. SMI did not meaningfully enhanced classification relative to BMI (change in area under the ROC curve = 0.002; net reclassification improvement = 0.021; integrated discrimination improvement = - 0.003). Optimal cutpoints for BMI, %BF, and SMI varied substantially across race. Among Black women, a %BF cutpoint of 43.9% performed somewhat better than BMI (change in area under the ROC curve = 0.017; sensitivity = 0.69, specificity = 0.64). CONCLUSION: Some race-specific BMI and %BF cutpoints have moderate utility for identifying impaired physical function among midlife women.

Low grip strength predicts incident diabetes among mid-life women: the Michigan Study of Women's Health Across the Nation.

Background: skeletal muscle is the primary site of glucose uptake, yet the impact of age-related changes in muscle strength on diabetes risk is unknown. Methods: four hundred and twenty-four participants (60% Black, 40% White) from the Michigan site of the Study of Women's Health Across the Nation contributed annual grip strength measures and were followed from 1996 to 2012 to identify incident cases of diabetes. Diabetes was defined as self-reported physician-diagnosed diabetes, use of anti-diabetic medications or measured fasting glucose ≥126 mg/dl or haemoglobin A1c > 6.5%. Results: the 16-year diabetes incidence was 37%. The average baseline weight-normalised grip strength (NGS, kg per kg body weight) was 0.41 ± 0.12 and a mean of 0.29 ± 0.14 kg of absolute grip strength was lost per year. Each 0.1 higher NGS was associated with a 19% lower hazard of incident diabetes (P = 0.006) after adjustment for age, race/ethnicity, economic strain, smoking, menopause status, hormone use, physical activity and waist-hip ratio. In race/ethnic-stratified models, each 0.10 increase in NGS was associated with a 54% lower hazard of incident diabetes (P < 0.0001) among White women but the association among Black women was not statistically significant. In models without adjustment for waist-hip ratio or restricted to women <48 years of age at baseline, there was a statistically significant association between baseline NGS and incident diabetes among Black women. The rate of change in grip strength was not associated with diabetes incidence. Conclusion: the mid-life is an important risk period for diabetes onset. Improving muscle strength. during mid-life may contribute to preventing diabetes among women.

Physical activity trajectories during midlife and subsequent risk of physical functioning decline in late mid-life: The Study of Women's Health Across the Nation (SWAN).

The purpose of this study was to examine the importance of midlife physical activity on physical functioning in later life. Data are from 1771 Study of Women's Health Across the Nation (SWAN) participants, aged 42-52 (46.4±2.7) years at baseline (1996-97). Latent class growth analysis was used to identify physical activity trajectory groups using reported sports and exercise index data collected at seven time-points from baseline to Visit 13 (2011-13); objective measures of physical functioning performance were collected at Visit 13. The sports and exercise index (henceforth: physical activity) is a measure of moderate to vigorous intensity physical activity during discretionary periods of the day. Multivariable linear regression analyses were used to model each continuous physical performance measure as a function of the physical activity trajectory class. Across midlife, five physical activity trajectory classes emerged, including: lowest (26.2% of participants), increasing (13.4%), decreasing (22.4%), middle (23.9%), and highest (14.1%) physical activity. After full adjustment, women included in the middle and highest physical activity groups demonstrated ≥5% better physical functioning performance than those who maintained low physical activity levels (all comparisons; p<0.05). Statistically significant differences were also noted when physical activity trajectory groups were compared to the increasing physical activity group. Results from the current study support health promotion efforts targeting increased (or maintenance of) habitual physical activity in women during midlife to reduce future risk of functional limitations and disability. These findings have important public health and clinical relevance as future generations continue to transition into older adulthood.

Childhood Socioeconomic Circumstances, Inflammation, and Hemostasis Among Midlife Women: Study of Women's Health Across the Nation.

BACKGROUND: Childhood socioeconomic status (SES) is related to risk for cardiovascular disease in adulthood, perhaps, in part, due to associations with inflammatory and hemostasis processes. We tested the hypotheses that childhood SES is related to C-reactive protein (CRP), fibrinogen, factor VIIc, and plasminogen activator inhibitor-1 (PAI-1) in midlife women and that the associations are mediated by adult SES and/or adult body mass index (BMI). METHODS: Using data from the prospective Study of Women's Health Across the Nation, we classified 1067 black and white women into 3 multidimensional childhood SES groups based on latent class analysis. Biological measures were assessed across 7 years along with covariates and mediators and analyzed by mixed regression models, followed by tests for mediation. RESULTS: Compared with women raised in high SES families, those from the lowest SES families had higher levels of CRP (b [standard error] = 0.37 [0.11]), PAI-1 (b = 0.23 [0.07]) factor VIIc (b = 0.05 [0.02]), and fibrinogen (b = 11.06 [4.89]), after adjustment for ethnicity, site, age, ratings of health between ages 11 and 18 years, visit, smoking status, menopausal status, stroke or heart attack, medications, and hormone use. Introduction of adult SES and BMI into the models reduced the childhood SES associations to nonsignificance for all four measures. Indirect mediation was apparent for adult education and BMI for CRP, and BMI for PAI-1. CONCLUSIONS: Women raised in lower SES families had elevated markers of inflammation and hemostasis, in part, due to elevated BMI and education in adulthood.

Is self-reported physical functioning associated with incident cardiometabolic abnormalities or the metabolic syndrome?

BACKGROUND: Physical functioning may be an important pre-clinical marker of chronic disease, used as a tool to identify patients at risk for future cardiometabolic abnormalities. This study evaluated if self-reported physical functioning was associated with the development of cardiometabolic abnormalities or their clustering (metabolic syndrome) over time. METHODS: Participants (n = 2,254) from the Study of Women's Health Across the Nation who reported physical functioning on the Short Form health survey and had a metabolic syndrome assessment (elevated fasting glucose, blood pressure, triglycerides and waist circumference; reduced HDL cholesterol) in 2000 were included. Discrete survival analysis was used to assess the 10-year risk of developing metabolic syndrome or a syndrome component through 2010. RESULTS: At baseline, the prevalence of metabolic syndrome was 22.0%. Women with substantial limitations (OR = 1.60; 95% CI: 1.12, 2.29) in physical functioning were significantly more likely to develop the metabolic syndrome compared with women reporting no limitations. Self-reported physical functioning was significantly associated with incident hypertension and increased waist circumference. CONCLUSIONS: Simple screening tools for cardiometabolic risk in clinical settings are needed. Self-reported physical functioning assessments are simple tools that may allow healthcare providers to more accurately predict the course of chronic conditions.

Diabetes and Menopause.

During menopause, women's body composition, sex hormone profile, and metabolic profile may change dramatically. In this review, we summarize studies examining whether the menopausal transition and physiologic factors characterizing the transition are associated with increased risk of diabetes. We review the evidence for estrogen therapy and diabetes risk and studies examining the relationship between diabetes and menarche, which represents an extension of the reproductive life span at the opposite end of the age spectrum. Although studied less extensively, the presence of type 1 or type 2 diabetes may increase the risk of ovarian failure, and we review this literature. In conclusion, we note that the evidence linking menopausal sex hormone changes with increased diabetes risk is weak, although rapid changes as observed with oophorectomy may increase risk. Further studies should investigate the contradictory effects of estrogen therapy upon hepatic and glucose metabolism in mid-life women.