Cardiovascular risk and midlife cognitive decline in the Study of Women's Health Across the Nation.

INTRODUCTION: Cardiovascular risk factors in midlife have been linked to late life risk for Alzheimer's disease and related dementias (ADRD). The relation of vascular risk factors on cognitive decline within midlife has been less studied. METHODS: Using data from the Study of Women's Health Across the Nation, we examined associations of midlife hypertension, elevated lipid levels, diabetes, fasting glucose, central adiposity, and Framingham heart age with rates of cognitive decline in women who completed multiple cognitive assessments of processing speed, and working and verbal memory during midlife. RESULTS: Diabetes, elevated fasting glucose, central obesity, and heart age greater than chronological age were associated with rate of decline in processing speed during midlife. Vascular risk factors were not related to rate of decline in working or verbal memory. DISCUSSION: Midlife may be a critical period for intervening on cardiovascular risk factors to prevent or delay later life cognitive impairment and ADRD.

Association of Longitudinal Glycemia with Diffusion Weighted Imaging Lesions in Spontaneous Intracerebral Hemorrhage.

OBJECTIVES: Higher glycemia on admission has been associated with diffusion weighted imaging (DWI) lesions in patients with spontaneous intracerebral hemorrhage (sICH). However, the influence of longitudinal glycemia after admission and during a patient's hospitalization on DWI lesions in sICH has not been studied. Our aim was to compare longitudinal glycemia in sICH patients with and without DWI lesions. MATERIAL AND METHODS: Glycemia measurements were abstracted on participants enrolled in a prospective observational study examining predictors for DWI lesions in sICH. Univariate analysis was used to compare mean longitudinal glycemia in sICH patients with and without DWI lesions. Logistical regression was used to determine whether mean longitudinal glycemia was predictive of DWI lesions. RESULTS: DWI lesions were found in 60 of the 121 (49.6%) participants. Mean time-to-MRI was 99.6 h (SD ± 89). During this time interval, 2,101 glucose measurements were analyzed with a median number of 7 (IQR 12, 1-261) measurements per patient. Mean longitudinal glycemia was higher in the DWI positive group compared to the DWI negative group until time-to-MRI (132 mg/dL vs 122 mg/dL, p = 0.03). Mean longitudinal glycemia was found to be predictive of DWI lesions (OR 1.02, 95% CI 1.005 to 1.035, p = 0.011). CONCLUSIONS: Mean longitudinal glycemia was higher in sICH patients with DWI lesions compared to those without DWI lesions. Future research into the association between higher glycemia and DWI lesions in sICH may provide insight into a pathophysiologic mechanism.

Sleep medications and sleep disturbances across middle aged pre- or peri-menopausal women of different race and ethnicities: A SWAN pharmacoepidemiology cohort study.

PURPOSE: Sleep disturbances are common, particularly in middle aged women. Prescription medications for this indication are increasingly used, despite uncertain safety. This study assessed prescription medication use for sleep among a cohort of women with and without sleep disturbances. METHODS: We examined reports of sleep disturbance and sleep medication use among pre- and early peri-menopausal womenassessed annually or biennially since 1996. Women self-reported medications at visits, and we identified medications that have been used primarily for sleep disturbances. They reported on difficulties falling and staying asleep, and early morning wakening. Sleep medication use across 20 years of follow-up was examined for all women and by race/ethnicity. Women who reported data for both sleep disturbance and sleep medication use were included in the analyses.. RESULTS: Among participants in a cohort of 3302 women who were enrolled prior to their menopause transition, 3082 women were included in the analytic sample and 2531 (82%) reported sleep disturbances. They were more likely to endorse higher anxiety and pain scores and more comorbid conditions than women without sleep disturbances. Baseline characteristics were similar among women who did and did not use sleep medications. Among women reporting a sleep disturbance at baseline, 2.5% reported sleep medication use, increasing to 8% over 20 years. However, the proportion of women reporting sleep medication use who did not report a sleep disturbance remained low, approximately 1% to 2% over the entire follow-up. Increases in sleep medication use was observed across women of all race/ethnicities. CONCLUSIONS: The use of sleep medications among women reporting sleep disturbance grew over the last 20 years. Growth was observed across women of all race/ethnicities.

Does Season of Reported Dietary Intake Influence Diet Quality? Analysis From the Women's Health Initiative.

We evaluated the role of seasonality in self-reported diet quality among postmenopausal women participating in the Women's Health Initiative (WHI). A total of 156,911 women completed a food frequency questionnaire (FFQ) at enrollment (1993-1998). FFQ responses reflected intake over the prior 3-month period, and seasons were defined as spring (March-May), summer (June-August), fall (September-November), and winter (December-February). FFQ data were used to calculate the Alternate Healthy Eating Index (AHEI), a measure of diet quality that has a score range of 2.5-87.5, with higher scores representing better diet quality. In multivariable linear regression models using winter as the reference season, AHEI scores were higher in spring, summer, and fall (all P values < 0.05); although significant, the variance was minimal (mean AHEI score: winter, 41.7 (standard deviation, 11.3); summer, 42.2 (standard deviation, 11.3)). Applying these findings to hypothesis-driven association analysis of diet quality and its relationship with chronic disease risk (cardiovascular disease) showed that controlling for season had no effect on the estimated hazard ratios. Although significant differences in diet quality across seasons can be detected in this population of US postmenopausal women, these differences are not substantial enough to warrant consideration in association studies of diet quality.

Race/ethnic comparisons of waist-to-height ratio for cardiometabolic screening: The study of women's health across the nation.

OBJECTIVE: To compare the performance of waist-to-height ratio as a screening tool for cardiometabolic conditions - hypertension, prediabetes/diabetes, dyslipidemia, and subclinical inflammation - in 5 race/ethnic groups of mid-life women. METHODS: Waist-to-height ratio and 4 cardiometabolic conditions were assessed in 3033 premenopausal midlife women (249 Hispanic, 226 Chinese, 262 Japanese, 1435 European-American, and 861 African American). The areas under the receiver operating characteristic curve (AUROC) were compared across the five race/ethnic groups using waist-to-height ratio to determine the likelihood of the four cardiometabolic conditions. RESULTS: The performance of waist-to-height ratio to detect one or more cardiometabolic conditions was comparable among all race/ethnic groups (AUROC > 0.60, p = 0.252), and was good/fair (AUROC > 0.60) when hypertension, prediabetes/diabetes, dyslipidemia, or subclinical inflammation were analyzed separately. The performance of waist-to-height ratio of 0.50 was skewed towards higher specificity among groups with low prevalence of cardiometabolic conditions and lower median waist-to-height ratio, and towards higher sensitivity among groups with high prevalence of cardiometabolic conditions and higher median waist-to-height ratio. CONCLUSIONS: Waist-to-height ratio can be used for community-based screening of mid-life women who may need secondary prevention for cardiometabolic conditions. A simple public health message: "Keep your waist to less than half of your height" applies to midlife women.

Birthweight, mediating biomarkers and the development of type 2 diabetes later in life: a prospective study of multi-ethnic women.

AIMS/HYPOTHESIS: The aim of this work was to investigate the prospective relationship between low birthweight (LBW) and type 2 diabetes risk later in life and the mediation effects of type 2 diabetes biomarkers linking LBW to type 2 diabetes risk. METHODS: We measured baseline plasma concentrations of various type 2 diabetes biomarkers in 1,259 incident type 2 diabetes cases and 1,790 controls in the Women's Health Initiative-Observational Study. Self-report birthweights of the participants were recorded. The total effect of LBW on type 2 diabetes risk was partitioned into effects that were mediated by a specific biomarker and effects that were not mediated by this biomarker, using counterfactual model-based mediation analysis. RESULTS: LBW was significantly associated with increased risk of type 2 diabetes. Compared with women with birthweight 3.63-4.54 kg, women with LBW (<2.72 kg) had a multivariable-adjusted OR of 2.15 (95% CI, 1.54, 3.00). Insulin resistance (indicated by HOMA-IR) mediated 47% of the total effect. Decreased sex hormone-binding globulin (SHBG) concentration accounted for 24%, elevated E-selectin concentration accounted for 25% and increased systolic blood pressure accounted for 8% of the total effect of LBW on type 2 diabetes risk. (Due to interactions among different mediators, the sum of each individual mediator's contribution could exceed 100%, without an upper limit.) CONCLUSIONS/INTERPRETATION: LBW is directly predictive of higher risk of type 2 diabetes later in life. The effect of LBW on type 2 diabetes risk seems mainly mediated by insulin resistance, which is further explained by circulating levels of SHBG and E-selectin and systolic blood pressure. The study provides potential risk stratification in a population at greater risk of developing type 2 diabetes.

Diet drink consumption and the risk of cardiovascular events: a report from the Women's Health Initiative.

BACKGROUND: Data are limited regarding the influence of diet drink consumption on cardiovascular disease (CVD) outcomes. OBJECTIVE: We aimed to evaluate the relationship between diet drink intake and cardiovascular events. DESIGN: We conducted a retrospective cohort study, utilizing data from the national, multicenter Women's Health Initiative Observational Study (WHI OS), recruiting subjects from 1993 to 1998. PATIENTS: Post-menopausal women with available diet drink intake data, without pre-existing CVD and who survived ≥ 60 days were included in the study. MAIN MEAURES: A composite of incident coronary heart disease, heart failure, myocardial infarction, coronary revascularization procedure, ischemic stroke, peripheral arterial disease and CVD death was used as the primary outcome. CVD death and all-cause mortality were secondary outcomes. Adjusted Cox proportional hazards models were used to compare primary and secondary outcomes across diet drink intake strata. KEY RESULTS: In all, 59,614 women, mean age 62.8 years, were included for analysis. In unadjusted analysis over a follow-up of 8.7 ± 2.7 years, the primary outcome occurred in 8.5 % of the women consuming ≥ 2 diet drinks/day, compared to 6.9 %, 6.8 % and 7.2 % in the 5-7/week, 1-4/week and 0-3/month groups, respectively. After controlling for other CVD risk factors, women who consumed ≥ 2 drinks/day had a higher adjusted risk of CVD events (HR 1.3, 95 % CI 1.1-1.5), CVD mortality (HR 1.5, 95 % CI 1.03-2.3) and overall mortality (HR 1.3, 95 % CI 1.04-1.5) compared to the reference group (0-3 drinks/month). CONCLUSIONS: This analysis demonstrates an association between high diet drink intake and CVD outcomes and mortality in post-menopausal women in the WHI OS.

Meal preparation and cleanup time and cardiometabolic risk over 14 years in the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: To determine whether baseline levels and longitudinal changes in meal preparation and cleanup time are associated with changes in cardiometabolic risk factors in midlife women. METHODS: Subjects were 2755 midlife women enrolled in the Study of Women's Health Across the Nation, a multi-ethnic, longitudinal cohort study in the United States. The five diagnostic components of the metabolic syndrome and meal preparation/cleanup time were assessed repeatedly across 14 years of follow-up (spanning 1996-2011) at seven U.S. sites. Mixed-effects logistic and ordered logistic models tested associations between meal preparation/cleanup time and odds of meeting criteria for metabolic syndrome and its individual diagnostic components. RESULTS: Women who spent more time preparing and cleaning up meals at baseline, or demonstrated greater increases in this activity, had greater increases over time in their odds of having metabolic syndrome and in the number of metabolic syndrome components for which they met criteria. Adjusted associations were observed between meal preparation/cleanup time and hypertension, impaired fasting glucose, hypertriglyceridemia, and low high-density lipoprotein cholesterol, but not abdominal obesity. CONCLUSIONS: In midlife women, greater meal preparation/cleanup time is associated with the development of an adverse cardiometabolic risk profile. Public health interventions should place greater emphasis on cooking healthfully, not just cooking frequently.

The value of diastolic function parameters in the prediction of left atrial appendage thrombus in patients with nonvalvular atrial fibrillation.

BACKGROUND: Left ventricular diastolic impairment and consequently elevated filling pressure may contribute to stasis leading to left atrial appendage thrombus (LAAT) in nonvalvular atrial fibrillation (AF). We investigated whether transthoracic echocardiographic parameters can predict LAAT independent of traditional clinical predictors. METHODS: We conducted a retrospective cohort study of 297 consecutive nonvalvular AF patients who underwent transthoracic echocardiogram followed by a transesophageal echocardiogram within one year. Multivariate logistic regression analysis models were used to determine factors independently associated with LAAT. RESULTS: Nineteen subjects (6.4%) were demonstrated to have LAAT by transesophageal echocardiography. These patients had higher mean CHADS2 scores [2.6 ± 1.2 vs. 1.9 ± 1.3, P = 0.009], higher E:e' ratios [16.6 ± 6.1 vs. 12.0 ± 5.4, P = 0.001], and lower mean e' velocities [6.5 ± 2.1 cm/sec vs. 9.1 ± 3.2 cm/sec, P = 0.001]. Both E:e' and e' velocity were associated with LAAT formation independent of the CHADS2 score, warfarin therapy, left ventricular ejection fraction (LVEF), and left atrial volume index (LAVI) [E:e' odds-ratio = 1.14 (95% confidence interval = 1.03 - 1.3), P = 0.009; e' velocity odds-ratio = 0.68 (95% confidence interval = 0.5 - 0.9), P = 0.007]. Similarly, diastolic function parameters were independently associated with spontaneous echo contrast. CONCLUSION: The diastolic function indices E:e' and e' velocity are independently associated with LAAT in nonvalvular AF patients and may help identify patients at risk for LAAT.

Body image satisfaction and depression in midlife women: the Study of Women's Health Across the Nation (SWAN).

With aging, women's bodies undergo changes that can affect body image perception, yet little is known about body image in midlife. The purpose of this study was to examine associations between body image and depressive symptoms in Caucasian and African-American midlife women from the Study of Women's Health Across the Nation (SWAN) Chicago site. Body image was measured using the Stunkard Adult Female Figure Rating Scale, and a clinically significant level of depressive symptoms was defined as Center for Epidemiologic Studies Depression Scale (CES-D) score of ≥16 (N=405; N=63 (15.6%) with clinically significant levels of depressive symptoms). Differences between perceived actual, perceived ideal, and actual body size and responses to questions concerning weight satisfaction and attractiveness were examined using logistic regression for associations with a CES-D score of ≥16. Women with body image dissatisfaction (odds ratio (OR)=1.91; p=0.04) or who perceived themselves as "unattractive" (OR=7.74; p<0.01) had higher odds of CES-D of ≥16. We found no significant difference by race. Our results were not confounded by BMI. These results suggest that midlife women with poor body image may be more likely to have clinically significant levels of depressive symptoms. Larger prospective studies are needed to better understand this association.

B-type natriuretic peptide predicts left atrial appendage thrombus in patients with nonvalvular atrial fibrillation.

PURPOSE: To investigate whether plasma B-type Natriuretic peptide (BNP), a surrogate of left ventricular filling pressure (LVFP), is predictive of left atrial appendage thrombus (LAAT) in patients with nonvalvular atrial fibrillation (AF) independent of known clinical risk predictors. METHODS: We conducted a retrospective cohort study of 297 consecutive subjects with AF who underwent a clinically indicated transesophageal echocardiogram (TEE) to evaluate for LAAT and spontaneous echo contrast (SEC). Among those, 136 had a clinically indicated BNP level. Using multivariate logistic regression analysis models, we determined factors independently predictive of the primary endpoint of LAAT and the secondary endpoint of either LAAT or SEC. RESULTS: Nineteen subjects (6.4%) had LAAT and they were found to have a higher mean CHADS2 score (2.53 vs 1.76, P = 0.01) and mean BNP level [1949 vs. 819 pg/mL, P = 0.001] than those without LAAT. None of the patients with a BNP level ≤500 pg/mL had LAAT. Multivariate logistic regression analysis demonstrated that BNP was predictive of LAAT and the composite of LAAT/SEC independent of the CHADS2 score and warfarin therapy [OR = 1.23 and 1.6 per 500 pg/mL increment in BNP, P-values = 0.03 and 0.001; respectively]. Moreover, adding BNP to the predictive model negated the influence of the CHADS2 score. CONCLUSION: These data indicate that BNP is an independent predictor of LAAT in AF and may complement the role of the CHADS2 score in predicting stroke risk.

Identifying the necessary capacities for the adaptation of a diabetes phenotyping algorithm in countries of differing economic development status.

BACKGROUND: In 2019, the World Health Organization recognised diabetes as a clinically and pathophysiologically heterogeneous set of related diseases. Little is currently known about the diabetes phenotypes in the population of low- and middle-income countries (LMICs), yet identifying their different risks and aetiology has great potential to guide the development of more effective, tailored prevention and treatment. OBJECTIVES: This study reviewed the scope of diabetes datasets, health information ecosystems, and human resource capacity in four countries to assess whether a diabetes phenotyping algorithm (developed under a companion study) could be successfully applied. METHODS: The capacity assessment was undertaken with four countries: Trinidad, Malaysia, Kenya, and Rwanda. Diabetes programme staff completed a checklist of available diabetes data variables and then participated in semi-structured interviews about Health Information System (HIS) ecosystem conditions, diabetes programme context, and human resource needs. Descriptive analysis was undertaken. RESULTS: Only Malaysia collected the full set of the required diabetes data for the diabetes algorithm, although all countries did collect the required diabetes complication data. An HIS ecosystem existed in all settings, with variations in data hosting and sharing. All countries had access to HIS or ICT support, and epidemiologists or biostatisticians to support dataset preparation and algorithm application. CONCLUSIONS: Malaysia was found to be most ready to apply the phenotyping algorithm. A fundamental impediment in the other settings was the absence of several core diabetes data variables. Additionally, if countries digitise diabetes data collection and centralise diabetes data hosting, this will simplify dataset preparation for algorithm application. These issues reflect common LMIC health systems' weaknesses in relation to diabetes care, and specifically highlight the importance of investment in improving diabetes data, which can guide population-tailored prevention and management approaches.

High serum levels of free cortisol indicate severity of cirrhosis in hemodynamically stable patients.

BACKGROUND AND AIM: We investigated: (i) the association between severity of cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC), measured before and 30 min after (T(30)) the low-dose 1-µg short synacthen test (LD-SST); and (ii) the prognostic value of SFC and STC. METHODS: Consecutive, hemodynamically stable, cirrhotic patients (34 Child-Pugh class A, 29B, and 32C) underwent the LD-SST. Patients were followed for at least 12 months to assess non-transplant-related mortality. RESULTS: Child-Pugh class C patients had significantly higher basal levels of SFC than Child-Pugh class A or B patients. Prevalence of suspected adrenal dysfunction ranged between 7.4% (T(0) STC < 138 nmol/L) and 49.4% (change in STC < 250 nmol/L) according to the threshold used. In receiver-operator curve analysis, the area-under-the-curve values were 0.67 for T(30) SFC (0.51-0.79), 0.81 for Child-Pugh score (0.70-0.88), and 0.79 for albumin level (0.63-0.88). During the follow-up period, 16 patients with high T(30) SFC (≥ 78.9 nmol/L) (26.2%) and one patient with low T(30) SFC (< 78.9 nmol/L) (3.4%) died (P = 0.027 for high vs low T(30) SFC, log-rank test). Albeit not statistically significant, the risk of death for patients with T(30) SFC ≥ 78.9 nmol/L was fivefold higher than for patients with lower levels after adjusting for cirrhosis severity and level of albumin. CONCLUSIONS: One-year, non-transplant-related mortality is high among patients with T(30) levels of SFC ≥ 78.9 nmol/L (26.2%). These findings might result from latent inflammatory stress in hemodynamically stable cirrhotic patients, detected by adrenal testing.

How well does the body adiposity index capture adiposity change in midlife women?: The SWAN fat patterning study.

OBJECTIVES: The body adiposity index (BAI) is a proposed alternative to the body mass index (BMI) that has shown good cross-sectional agreement with percent body fat (%BF) in validation studies. The objective of this study was to examine the ability of BAI to track adiposity change over time in a biracial sample of midlife women. METHODS: African-American (n = 159) and Caucasian (n = 206) women, aged 42-60 years, at the Chicago site of the Study of Women's Health Across the Nation were followed from 2002 to 2008. BAI and BMI were calculated from measurements taken at annual assessments. %BF was quantified using whole-body dual-energy X-ray absorptiometry. Difference scores (BAI(Δ) , BMI(Δ) , and %BF(Δ) ) quantified adiposity change over a mean of 1.6 (SD = 0.7) years. Lin's concordance correlation (ρ(c) ) and Bland-Altman limits-of-agreement assessed agreement between BAI and %BF. RESULTS: In examining adiposity change, BAI(Δ) showed poor agreement with %BF(Δ) in the overall sample (ρ(c) = 0.41), African-American women (ρ(c) = 0.36), and Caucasian women (ρ(c) = 0.43). BAI(Δ) estimated %BF(Δ) with minimal bias (+0.4%) but low precision (±6.3%BF limits-of-agreement). %BF(Δ) had weaker correlations with BAI(Δ) (rs = 0.38-0.48) than with BMI(Δ) (rs = 0.48-0.59). BAI and BMI showed similar cross-sectional associations with %BF in the overall sample and within each race (rs > 0.74). CONCLUSIONS: We conclude that BAI is less accurate than BMI in tracking adiposity change in midlife women, and would not be a suitable replacement for BMI in most research applications involving adiposity change.

Abdominal visceral adipose tissue over the menopause transition and carotid atherosclerosis: the SWAN heart study.

OBJECTIVES: To characterize abdominal visceral adipose tissue (VAT) trajectory relative to the final menstrual period (FMP), and to test whether menopause-related VAT accumulation is associated with greater average, common carotid artery intima-media thickness (cIMT) and/or internal carotid artery intima-media thickness (ICA-IMT). METHODS: Participants were 362 women (at baseline: age was (mean ±â€ŠSD) 51.1 ±â€Š2.8 y; 61% White, 39% Black) with no cardiovascular disease from the Study of Women's Health Across the Nation Heart study. Women had up to two measurements of VAT and cIMT over time. Splines revealed a nonlinear trajectory of VAT with two inflection points demarcating three time segments: segment 1: >2 years before FMP; segment 2: 2 years before FMP to FMP; and segment 3: after FMP. Piecewise-linear random-effects models estimated changes in VAT. Random-effects models tested associations of menopause-related VAT with each cIMT measure separately. Estimates were adjusted for age at FMP, body mass index, and sociodemographic, lifestyle, and cardiovascular disease risk factors. RESULTS: VAT increased significantly by 8.2% (95% CI: 4.1%-12.5%) and 5.8% (3.7%-7.9%) per year in segments 2 and 3, respectively, with no significant change in VAT within segment 1. VAT predicted greater ICA-IMT in segment 2, such that a 20% greater VAT was associated with a 2.0% (0.8%-3.1%) greater ICA-IMT. VAT was not an independent predictor of ICA-IMT in the other segments or of the other cIMT measures after adjusting for covariates. CONCLUSIONS: Women experience an accelerated increase in VAT starting 2 years before menopause. This menopause-related increase in VAT is associated with greater risk of subclinical atherosclerosis in the internal carotid artery.

Video Summary:http://links.lww.com/MENO/A722 .

Patterns of menstrual cycle length over the menopause transition are associated with subclinical atherosclerosis after menopause.

OBJECTIVE: Longer menstrual cycles have been associated with greater risk of cardiovascular disease, supporting a contribution of abnormal ovarian function. We aimed to characterize trajectories of menstrual cycle length over the menopause transition (MT) and test whether these trajectories are associated with postmenopausal markers of subclinical atherosclerosis. METHODS: Women from the Study of Women's Health Across the Nation Daily Hormone Study were included if they had an observed date of the final menstrual period (FMP), recorded cycle lengths from ≥2 annual menstrual cycles (mean±SD: 4.22 ± 1.91 cycles), and had measurements of postmenopausal carotid intima-media thickness (cIMT) and/or brachial-ankle pulse wave velocity (baPWV). Trajectories of cycle length over the MT were identified using group-based trajectory modeling and linked with cIMT and baPWV using linear regression. RESULTS: We studied 428 women who had 1,808 cycles over the MT (45.1 ± 2.3 y old at baseline visit), and of whom 263 had cIMT, and 213 had baPWV measured postmenopausally (after 13.88 ±â€Š0.42 and 15.25 ±â€Š0.70 y since baseline visit, respectively). Three distinct trajectories of cycle length were identified: stable (no changes in cycle length over the MT among 62.1% of women), late increase (a late increase 2 y before the FMP among 21.8%), and early-increase (an early increase 5 y before the FMP among 16.2%). Women with the late-increase pattern had significantly lower postmenopausal cIMT (0.72 mm) and baPWV (1392 cm/s) levels than the stable group (0.77 mm and 1508 cm/s, respectively) adjusting for race, concurrent age, socioeconomic status, physical activity level, and premenopausal cardiovascular risk profile. CONCLUSIONS: Patterns of cycle length over the MT seem to be a marker of future vascular health that may help identify groups at greater or lesser risk of atherosclerosis after menopause.

Lowered progesterone metabolite excretion and a variable LH excretion pattern are associated with vasomotor symptoms but not negative mood in the early perimenopausal transition: Study of Women's Health Across the Nation.

OBJECTIVE: The menopausal transition is characterized by progressive changes in ovarian function and increasing circulating levels of gonadotropins, with some women having irregular menstrual cycles well before their final menstrual period. These observations indicate a progressive breakdown of the hypothalamic-pituitary-ovarian axis often associated with an increase in menopausal symptoms. Relationships between vasomotor symptoms (VMS) and depressed mood and sleep as well as a bidirectional association between VMS and depressed mood in mid-life women have been reported, but the endocrine foundations and hormone profiles associated with these symptoms have not been well described. Our objective was to determine the relationship between daily urinary hormone profiles and daily logs of affect and VMS during the early perimenopausal transition. STUDY DESIGN: SWAN, the Study of Women's Health Across the Nation, is a large, mutli-ethnic, multisite cohort study of 3302 women aged 42-52 at baseline, designed to examine predictors of health and disease in women as they traversed the menopause. Inclusion criteria were: an intact uterus and at least one ovary present, at least one menstrual period in the previous three months, no use of sex steroid hormones in the previous three months, and not pregnant or lactating. A subset (n = 849) of women aged 43-53 years from all study sites in the first Daily Hormone Study collection were evaluated for this substudy. OUTCOME MEASURES: We measured daily VMS, and urinary hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), pregnanediol glucuronide (PdG) and estradiol (estrone conjugate, E1C). RESULTS: A variable pattern of LH and negative LH feedback were the hormone patterns most strongly associated with increased VMS. In contrast, no hormone pattern was significantly related to negative mood. CONCLUSION: Fluctuations of LH associated with low progesterone production were associated with VMS but not negative mood, suggesting different endocrine patterns may be related to increased negative mood than to the occurrence of VMS.

Is race or ethnicity associated with under-utilization of statins among women in the United States: The study of women's health across the nation.

BACKGROUND: Rates of statin use among minority women are unclear. HYPOTHESIS: We hypothesized that statin use would vary by race/ethnicity with lower rates among minority women compared with Whites. METHODS: Data from the study of women's health across the nation, a multiethnic cohort of women collected between 2009 to 2011 were used to examine reported statin use by race/ethnicity and risk profile. Multivariable logistic modeling was performed to estimate the odds ratio (OR) of statin treatment. RESULTS: Of the 2399 women included, 234 had a diagnosis of atherosclerotic disease (ASCVD), 254 were diabetic (without ASCVD), 163 had an LDL ≥190 mg/dL, and 151 had a 10 year ASCVD pooled risk score ≥7.5%. Statins were used by 49.6% of women with CVD; 59.8% of women with diabetes without known ASCVD; 42.3% of women with an LDL ≥190 mg/dL; and 19.9% of women with an ASCVD risk ≥7.5%. Rates of statin use were 43.8% for women with ≥ two prior ASCVD events and 69.4% for women with ≥ one prior ASCVD event plus multiple high-risk conditions. Among women eligible for statins, Black women had a significantly reduced adjusted odds of being on a statin (OR 0.53, 95% confidence interval [CI] 0.36-0.78) compared with White women. CONCLUSIONS: In this cohort of multiethnic women, rates of statin use among women who would benefit were low, with Black women having lower odds of statin use than White women.

Is Midlife Metabolic Syndrome Associated With Cognitive Function Change? The Study of Women's Health Across the Nation.

CONTEXT: Metabolic syndrome (MetS) affects cognitive function in late life, particularly in women. But longitudinal research is scarce on associations of MetS with cognitive function during midlife. OBJECTIVE: To determine associations between MetS exposure and cognitive function trajectories in midlife women. DESIGN AND SETTING: This is a 17-year prospective, longitudinal study of multiracial/ethnic women in 7 US communities, with annual/biennial assessments. PARTICIPANTS: Participants were 2149 US women traversing menopause. EXPOSURE: Exposure consisted of MetS assessments (median 4 assessments over 4 years). MAIN OUTCOME MEASURES: Main outcome measures were assessments of cognitive function in 3 domains: perceptual speed (symbol digit modalities test, SDMT), episodic memory (East Boston Memory Test, EBMT), and working memory (Digit Span Backward Test, DSB). RESULTS: By their first cognitive assessment (age 50.7 ± 2.9 years), 29.5% met the criteria for MetS. Women completed a median (interquartile range [IQR]) of 6 (IQR 4-7) follow-up cognitive assessments over 11.2 (IQR 9.2-11.5) years. Women with MetS, compared with those without, had a larger 10-year decline in SDMT z-score (estimate -0.087, 95% confidence interval, -0.150 to -0.024; P = 0.007), after adjustment for cognitive testing practice effects, sociodemographics, lifestyle, mood, and menopause factors. As such, MetS accelerated the 10-year loss of perceptual speed by 24%. MetS did not differentially affect the rate of decline in either immediate (P = 0.534) or delayed (P = 0.740) episodic memory or in working memory (P = 0.584). CONCLUSIONS: In midlife women MetS exposure was associated with accelerated decline in perceptual speed, but not episodic or working memory.

Impact of Chronic Medical Condition Development on Longitudinal Physical Function from Mid- to Early Late-Life: The Study of Women's Health Across the Nation.

BACKGROUND: Chronic medical conditions (CMCs) often emerge and accumulate during the transition from mid- to late-life, and the resulting multimorbidity can greatly impact physical function. We assessed the association of CMC presence and incidence on trajectories of physical function from mid- to early late-life in the Study of Women's Health Across the Nation. METHODS: Physical function was assessed at eight clinic visits (average 14 years follow-up) using the physical function subscale of the Short Form-36. CMCs included osteoarthritis, diabetes, stroke, hypertension, heart disease, cancer, osteoporosis, and depressive symptomatology, and were considered cumulatively. Repeated-measures Poisson models estimated longitudinal change (expressed as percent difference) in physical function by chronic CMCs. Change-points assessed physical function change coincident with the development of a new condition. RESULTS: Women (N = 2,283) followed from age 50.0 ± 2.7 to 64.0 ± 3.7 years; 7.3% had zero CMCs through follow-up, 22.5% (N = 513) had no baseline CMCs but developed ≥1, 22.7% women had ≥1 baseline CMC but never developed another, and 47.6% had ≥1 baseline CMC and developed ≥1 more. Each additional baseline CMC was associated with 4.0% worse baseline physical function and annual decline of 0.20%/year. Women with more baseline CMCs had greater decline in physical function with a new CMC (-1.90% per condition); and annual decline when developing a new condition accelerated by -0.33%/year per condition. CONCLUSIONS: Self-reported physical function changes are evident from mid- to early late-life with the development of CMCs. Preventing or delaying CMCs may delay declines in physical function, and these potential pathways to disability warrant further research.