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 .

HDL (High-Density Lipoprotein) Subclasses, Lipid Content, and Function Trajectories Across the Menopause Transition: SWAN-HDL Study.

OBJECTIVE: The cardioprotective capacity of HDL (high-density lipoprotein) cholesterol postmenopause has been challenged. HDL subclasses, lipid contents, and function might be better predictors of cardiovascular risk than HDL cholesterol. Changes in these measures have not been characterized over the menopause transition (MT) with respect to timing relative to the final menstrual period. Approach and Results: Four hundred seventy-one women with HDL particle (HDL-P) subclasses (nuclear magnetic resonance spectroscopy total, large, medium, and small HDL-P and HDL size), HDL lipid content (HDL phospholipids and triglycerides), and HDL function (cholesterol efflux capacity [HDL-CEC]) measured for a maximum of 5 time points across the MT were included. HDL cholesterol and total HDL-P increased across the MT. Within the 1 to 2 years bracketing the final menstrual period, large HDL-P and HDL size declined while small HDL-P and HDL-triglyceride increased. Although overall HDL-CEC increased across the MT, HDL-CEC per HDL-P declined. Higher concentrations of total, large, and medium HDL-P and greater HDL size were associated with greater HDL-CEC while of small HDL-P were associated with lower HDL-CEC. Associations of large HDL-P and HDL size with HDL-CEC varied significantly across the MT such that higher large HDL-P concentrations and greater HDL size were associated with lower HDL-CEC within the 1 to 2 years around the final menstrual period. CONCLUSIONS: Although HDL cholesterol increased over the MT, HDL subclasses and lipid content showed adverse changes. While overall HDL-CEC increased, HDL-CEC per HDL-P declined, consistent with reduced function per particle. Large HDL-P may become less efficient in promoting HDL-CEC during the MT.

Identifying women who share patterns of reproductive hormones, vasomotor symptoms, and sleep maintenance problems across the menopause transition: group-based multi-trajectory modeling in the Study of Women's Health Across the Nation.

OBJECTIVE: To identify groups of women who share levels and patterns of change in follicle-stimulating hormone (FSH), self-reported sleep maintenance problems, and frequent vasomotor symptoms (VMS) up to 10 years before and after their final menstrual period and to evaluate their premenopausal characteristics. METHOD: Group-based multi-trajectory modeling grouped 1,407 women from the Study of Women's Health Across the Nation who had an observed natural menopause and did not use hormone therapy, based on repeated measures of FSH, sleep maintenance problems, and frequent VMS relative to final menstrual period. Multivariable analyses assessed race/ethnicity, body mass index, smoking, and depressive symptoms as predictors of group membership. RESULTS: Women formed five distinct groups: (1) low symptoms (low VMS/sleep problems)/high FSH rise (N = 552; 39.2%); (2) moderate VMS and sleep problems/low FSH rise (N = 169; 12.0%); (3) dominant sleep problems (lower VMS/high sleep problems)/high FSH rise (N = 203; 14.4%); (4) dominant VMS (high VMS/lower sleep problems)/high FSH rise (N = 297; 21.1%)); and (5) high symptoms (high VMS/high sleep problems)/intermediate FSH rise (N = 186; 13.2%)). Multivariate analyses showed that race/ethnicity, premenopausal body mass index and depressive symptoms, and increasing depressive symptoms during the early phase of the transition predicted group membership. CONCLUSIONS: Women can be classified based on shared levels and patterns of FSH, sleep maintenance problems, and frequent VMS across the menopause transition. Either VMS or sleep maintenance problems can be dominant in the face of high FSH. Experiencing one menopause-related symptom or hormone profile does not automatically imply that another is also being experienced.

Arterial Stiffness Accelerates Within 1 Year of the Final Menstrual Period: The SWAN Heart Study.

OBJECTIVE: Menopause may augment age-dependent increases in arterial stiffness, with black women having greater progression in midlife compared with white women. We sought to determine whether and when women experience changes in arterial stiffness relative to the final menstrual period (FMP) and whether these changes differ between black and white midlife women. Approach and Results: We evaluated 339 participants from the SWAN (Study of Women's Health Across the Nation) Heart Ancillary study (Study of Women's Health Across the Nation). Women had ≤2 carotid-femoral pulse-wave velocity (cfPWV) exams over a mean±SD of 2.3±0.5 years of follow-up. Annual percentage changes in cfPWV were estimated in 3 time segments relative to FMP and compared using piecewise linear mixed-effects models. At baseline, women were 51.1±2.8 years of age and 36% black. Annual percentage change (95% CI) in cfPWV varied by time segments: 0.9% (-0.6% to 2.3%) for >1 year before FMP, 7.5% (4.1% to 11.1%) within 1 year of FMP, and -1.0% (-2.8% to 0.8%) for >1 year after FMP. Annual percentage change in cfPWV within 1 year of FMP was significantly greater than the other 2 time segments; P<0.05 for both comparisons. Adjusting for concurrent cardiovascular disease risk factors explained part of the change estimates but did not eliminate the difference. Black women had greater increase in cfPWV compared with white women in the first segment; P for interaction, 0.04. CONCLUSIONS: The interval within 1 year of FMP is a critical period for women when vascular functional alterations occur. These findings underscore the importance of more intensive lifestyle modifications in women transitioning through menopause.

Does midlife aging impact women's sleep duration, continuity, and timing?: A longitudinal analysis from the Study of Women's Health Across the Nation.

Our study objectives were to evaluate the age-related changes in actigraphy measures of sleep duration, continuity, and timing across 12 years in midlife women as they traversed the menopause, and to take into account factors affecting women's sleep that also change with age. Black, white, and Chinese women were recruited from the Study of Women's Health Across the Nation (SWAN) to participate in an ancillary sleep study on two occasions over 3 years apart and a third assessment 12 years after the first (N = 300, mean ages, 52, 55, and 64 at the three assessments). Women had at least four consecutive nights of actigraphy (95% with 7 nights) and sleep diaries, and self-reported sleep complaints measured at each time point. Partial correlations adjusted for time between assessments across the 12 years were significant and moderate in size (r's = .33-.58). PROC MIXED/GLIMMIX multivariate models showed that sleep duration increased over time; wake after sleep onset (WASO) declined, midpoint of sleep interval increased, and sleep latency and number of sleep complaints did not change between the first and third assessments. Blacks and whites had a greater increase in sleep duration than Chinese. Taken together, the results of this longitudinal study suggest that sleep may not worsen, in general, in midlife women. Perhaps, the expected negative effect of aging in midlife into early old age on sleep is overstated.

Hot flashes and awakenings among midlife women.

STUDY OBJECTIVES: For most women, the menopause is accompanied by hot flashes and sleep problems. Although hot flashes reportedly wake women from sleep, in the few studies that have used objective measures of both sleep and hot flashes, links between hot flashes and nocturnal awakening have been inconsistent. In a well-characterized cohort of midlife women, we examined the association between objectively assessed hot flashes and actigraphically defined wake from sleep. We hypothesized that wake episodes would be more likely during an objective hot flash relative to minutes without a hot flash. METHODS: Peri- and postmenopausal midlife women underwent simultaneous objective measurement of hot flashes (sternal skin conductance) and sleep (actigraphy) over 24 hours in the home. The likelihood of waking in the minutes during the hot flash relative to the minutes preceding the hot flash was compared using generalized estimating equations. RESULTS: We studied 168 women with at least one objective nocturnal hot flash and actigraphy data. Actigraphy-assessed wake episodes were concurrent with 78% of the objective hot flashes. We found an increased likelihood of wake in the minutes during the objective hot flash (0 to +5 min: OR [95% CI] = 5.31 (4.46 to 6.33); p < .0001) relative to the minutes preceding it (-10 to -1 min). The increased likelihood of wake occurred irrespective of whether the women reported the objective hot flash. CONCLUSION: Among these women who underwent objective measurement of sleep and hot flashes, nocturnal wakefulness was observed with the majority of hot flashes.

Racial/ethnic disparities in women's sleep duration, continuity, and quality, and their statistical mediators: Study of Women's Health Across the Nation.

STUDY OBJECTIVES: To describe racial/ethnic differences in sleep duration, continuity, and perceived sleep quality in postmenopausal women and to identify statistical mediators of differences in sleep characteristics. METHODS: Recruited from the observational Study of Women's Health Across the Nation (SWAN), 1,203 (548 white, 303 black, 147 Chinese, 132 Japanese, and 73 Hispanic; mean age 65 years, 97% postmenopausal) women participated in a week-long actigraphy and daily diary study in 2013-2015. Actigraphic measures of sleep duration and wake after sleep onset (WASO), and diary-rated sleep quality were averaged across the week. Candidate mediators included health-related variables; stress; and emotional well-being assessed up to 13 times across 18 years from baseline to sleep study. RESULTS: Whites slept longer than other groups; the significant mediators were concurrent financial hardship and increasing number of stressors for Hispanics or Japanese versus whites. Whites had less WASO than blacks and Hispanics; significant mediators were concurrent number of health problems, physical inactivity, waist circumference, vasomotor symptoms, number of life stressors, and financial hardship, and increasing number of health problems from baseline to sleep study. Whites reported better sleep quality than blacks, Chinese, and Japanese; significant mediators were concurrent physical inactivity, vasomotor symptoms, positive affect, and depressive symptoms. CONCLUSIONS: Sleep differences between blacks or Hispanics versus whites were mediated by health problems, number of stressors, and financial hardship, whereas sleep differences between Chinese or Japanese versus whites were mediated by emotional well-being. This is the first study using formal mediational approaches.

Physiologically assessed hot flashes and endothelial function among midlife women.

OBJECTIVE: Hot flashes are experienced by most midlife women. Emerging data indicate that they may be associated with endothelial dysfunction. No studies have tested whether hot flashes are associated with endothelial function using physiologic measures of hot flashes. We tested whether physiologically assessed hot flashes were associated with poorer endothelial function. We also considered whether age modified associations. METHODS: Two hundred seventy-two nonsmoking women reporting either daily hot flashes or no hot flashes, aged 40 to 60 years, and free of clinical cardiovascular disease, underwent ambulatory physiologic hot flash and diary hot flash monitoring; a blood draw; and ultrasound measurement of brachial artery flow-mediated dilation to assess endothelial function. Associations between hot flashes and flow-mediated dilation were tested in linear regression models controlling for lumen diameter, demographics, cardiovascular disease risk factors, and estradiol. RESULTS: In multivariable models incorporating cardiovascular disease risk factors, significant interactions by age (P < 0.05) indicated that among the younger tertile of women in the sample (age 40-53 years), the presence of hot flashes (beta [standard error] = -2.07 [0.79], P = 0.01), and more frequent physiologic hot flashes (for each hot flash: beta [standard error] = -0.10 [0.05], P = 0.03, multivariable) were associated with lower flow-mediated dilation. Associations were not accounted for by estradiol. Associations were not observed among the older women (age 54-60 years) or for self-reported hot flash frequency, severity, or bother. Among the younger women, hot flashes explained more variance in flow-mediated dilation than standard cardiovascular disease risk factors or estradiol. CONCLUSIONS: Among younger midlife women, frequent hot flashes were associated with poorer endothelial function and may provide information about women's vascular status beyond cardiovascular disease risk factors and estradiol.

Pathways Linking Childhood SES and Adult Health Behaviors and Psychological Resources in Black and White Men.

Background: Exposure to low socioeconomic status (SES) in childhood predicts increased morbidity and mortality. However, little prospective evidence is available to test pathways linking low childhood SES to adult health. Purpose: In the current study, indirect effects through positive parenting in adolescence and adult SES were tested in the association between childhood SES and adult health behaviors and psychological resources. Methods: Men (n = 305; 53% Black) were followed longitudinally from ages 7 to 32. SES was measured annually in childhood (ages 7-9) and again in adulthood (age 32) using the Hollingshead index. Parenting was assessed annually (ages 13-16) using caregivers' and boys' self-report of supervision, communication, and expectations for their son's future. Health behaviors (cigarette and alcohol use, fruit and vegetable consumption, and physical activity) and psychological resources (optimism, purpose in life, self-mastery, and self-esteem) were assessed in adulthood (age 32). Results: Structural equation modeling showed that higher childhood SES was associated with more positive parenting in adolescence and higher adult SES. Higher childhood SES was indirectly associated with healthier behaviors and higher psychological resources in adulthood through pathways involving positive parenting during adolescence and SES in adulthood. Findings were consistent in both racial groups. Conclusions: Positive parenting in adolescence was an important pathway in understanding associations among childhood SES and health behaviors and psychological resources in adulthood. Low childhood SES was prospectively associated with healthier behaviors and greater psychological resources in part through more positive parenting in adolescence.

Trauma exposure and endothelial function among midlife women.

OBJECTIVE: Trauma is a potent exposure that can have implications for health. However, little research has considered whether trauma exposure is related to endothelial function, a key process in the pathophysiology of cardiovascular disease (CVD). We tested whether exposure to traumatic experiences was related to poorer endothelial function among midlife women, independent of CVD risk factors, demographic factors, psychosocial factors, or a history of childhood abuse. METHODS: In all, 272 nonsmoking perimenopausal and postmenopausal women aged 40 to 60 years without clinical CVD completed the Brief Trauma Questionnaire, the Child Trauma Questionnaire, physical measures, a blood draw, and a brachial ultrasound for assessment of brachial artery flow-mediated dilation (FMD). Relations between trauma and FMD were tested in linear regression models controlling for baseline vessel diameter, demographics, depression/anxiety, CVD risk factors, health behaviors, and, additionally, a history of childhood abuse. RESULTS: Over 60% of the sample had at least one traumatic exposure, and 18% had three or more exposures. A greater number of traumatic exposures was associated with lower FMD, indicating poorer endothelial function in multivariable models (beta, ß [standard error, SE] -1.05 [0.40], P = 0.01). Relations between trauma exposure and FMD were particularly pronounced for three or more trauma exposures (b [SE] -1.90 [0.71], P = 0.008, relative to no exposures, multivariable). CONCLUSIONS: A greater number of traumatic exposures were associated with poorer endothelial function. Relations were not explained by demographics, CVD risk factors, mood/anxiety, or a by history of childhood abuse. Women with greater exposure to trauma over life maybe at elevated CVD risk.

Cardiovascular fat in women at midlife: effects of race, overall adiposity, and central adiposity. The SWAN Cardiovascular Fat Study.

OBJECTIVES: Cardiovascular fat (CF) is associated with greater coronary heart disease (CHD) risk. Postmenopausal women have greater CF volumes than premenopausal women, and the association between specific CF depot volumes and CHD risk is more pronounced after menopause. Race, central adiposity, and visceral adiposity are important factors that could impact CF volumes. Whether racial differences in CF volumes and in their associations with central (visceral fat [VAT]) and general adiposity (body mass index [BMI]) exist in midlife women have not been addressed before. METHODS: In all, 524 participants from the Study of Women's Health Across the Nation (mean age: 50.9 ±â€Š2.9 years; 62% White and 38% Black) who had data on CF volumes (epicardial fat [EAT], paracardial fat [PAT], total heart fat, and aortic perivascular fat), VAT, and BMI were studied. RESULTS: In models adjusted for age, study site, menopausal status, comorbid conditions, alcohol consumption, and physical activity, Black women had 19.8% less EAT, 24.5% less PAT, 20.4% less total heart fat, and 13.2% less perivascular fat than White women (all P < 0.001). These racial differences remained significant after additional adjustment for BMI or VAT. Race significantly modified associations between adiposity measures and CF volumes. Every 1-SD higher BMI was associated with 66.7% greater PAT volume in White compared with 42.4% greater PAT volume in Black women (P = 0.004), whereas every 1-SD higher VAT was associated with 32.3% greater EAT volume in Black compared with 25.3% greater EAT volume in White women (P = 0.039). CONCLUSIONS: Racial differences were found in CF volumes and in their associations with adiposity measures among midlife women. Future research should determine how race-specific changes in CF volumes impact CHD risk in women.

History of Adverse Pregnancy Outcomes, Blood Pressure, and Subclinical Vascular Measures in Late Midlife: SWAN (Study of Women's Health Across the Nation).

BACKGROUND: Adverse pregnancy outcomes, such as preterm birth (PTB), have been associated with elevated risk of maternal cardiovascular disease, but their effect on late midlife blood pressure (BP) and subclinical vascular measures remains understudied. METHODS AND RESULTS: We conducted a cross-sectional analysis with 1220 multiethnic parous women enrolled in SWAN (Study of Women's Health Across the Nation) to evaluate the impact of self-reported history of adverse pregnancy outcomes (PTB, small-for-gestational-age, stillbirth), on maternal BP, mean arterial pressure, and subclinical vascular measures (carotid intima-media thickness, plaque, and pulse wave velocity) in late midlife. We also examined whether these associations were modified by race/ethnicity. Associations were tested in linear and logistic regression models adjusting for sociodemographics, reproductive factors, cardiovascular risk factors, and medications. Women were on average aged 60 years and 255 women reported a history of an adverse pregnancy outcome. In fully adjusted models, history of PTB was associated with higher BP (systolic: ß=6.40; SE, 1.62 [P<0.0001] and diastolic: ß=3.18; SE, 0.98 [P=0.001]) and mean arterial pressure (ß=4.55; SE 1.13 [P<0.0001]). PTB was associated with lower intima-media thickness, but not after excluding women with prevalent hypertension. There were no significant associations with other subclinical vascular measures. CONCLUSIONS: Findings suggest that history of PTB is associated with higher BP and mean arterial pressure in late midlife. Adverse pregnancy outcomes were not significantly related to subclinical cardiovascular disease when excluding women with prevalent hypertension. Future studies across the menopause transition may be important to assess the impact of adverse pregnancy outcomes on midlife progression of BP.

Sleep-Wake Concordance in Couples Is Inversely Associated With Cardiovascular Disease Risk Markers.

Aim: To determine whether interdependence in couples' sleep (sleep-wake concordance i.e., whether couples are awake or asleep at the same time throughout the night) is associated with two markers of cardiovascular disease (CVD) risk, ambulatory blood pressure (BP) and systemic inflammation. Methods: This community-based study is a cross-sectional analysis of 46 adult couples, aged 18-45 years, without known sleep disorders. Percent sleep-wake concordance, the independent variable, was calculated for each individual using actigraphy. Ambulatory BP monitors measured BP across 48 h. Dependent variables included mean sleep systolic BP (SBP) and diastolic BP (DBP), mean wake SBP and DBP, sleep-wake SBP and DBP ratios, and C-reactive protein (CRP). Mixed models were used and were adjusted for age, sex, education, race, and body mass index. Results: Higher sleep-wake concordance was associated with lower sleep SBP (b = -.35, SE = .01) and DBP (b = -.22, SE = .10) and lower wake SBP (b = -.26, SE = .12; all p values < .05). Results were moderated by sex; for women, high concordance was associated with lower BP. Men and women with higher sleep-wake concordance also had lower CRP values (b = -.15, SE = .03, p < .05). Sleep-wake concordance was not associated with wake DBP or sleep/wake BP ratios. Significant findings remained after controlling for individual sleep quality, duration, and wake after sleep onset. Conclusions: Sleep-wake concordance was associated with sleep BP, and this association was stronger for women. Higher sleep-wake concordance was associated with lower systemic inflammation for men and women. Sleep-wake concordance may be a novel mechanism by which marital relationships are associated with long-term CVD outcomes.

Postmenopausal Women With Greater Paracardial Fat Have More Coronary Artery Calcification Than Premenopausal Women: The Study of Women's Health Across the Nation (SWAN) Cardiovascular Fat Ancillary Study.

BACKGROUND: Volumes of paracardial adipose tissue (PAT) and epicardial adipose tissue (EAT) are greater after menopause. Interestingly, PAT but not EAT is associated with estradiol decline, suggesting a potential role of menopause in PAT accumulation. We assessed whether volumes of heart fat depot (EAT and PAT) were associated with coronary artery calcification (CAC) in women at midlife and whether these associations were modified by menopausal status and estradiol levels. METHODS AND RESULTS: EAT and PAT volumes and CAC were measured using electron beam computed tomography scans. CAC was evaluated as (1) the presence of CAC (CAC Agatston score ≥10) and (2) the extent of any CAC (log CAC Agatston score >0). The study included 478 women aged 50.9 years (58% pre- or early perimenopausal, 10% late perimenopausal, and 32% postmenopausal). EAT was significantly associated with CAC measures, and these associations were not modified by menopausal status or estradiol. In contrast, associations between PAT and CAC measures were modified by menopausal status (interaction-P≤0.01). Independent of study covariates including other adiposity measures, each 1-SD unit increase in log PAT was associated with 102% higher risk of CAC presence (P=0.04) and an 80% increase in CAC extent (P=0.008) in postmenopausal women compared with pre- or early perimenopausal women. Additional adjustment for estradiol and hormone therapy attenuated these differences. Moreover, the association between PAT and CAC extent was stronger in women with lower estradiol levels (interaction P=0.004). CONCLUSIONS: The findings suggest that PAT is a potential menopause-specific coronary artery disease risk marker, supporting the need to monitor and target this fat depot for intervention in women at midlife.

Bedtime Variability and Metabolic Health in Midlife Women: The SWAN Sleep Study.

STUDY OBJECTIVES: Circadian misalignment, as seen in shift workers, can disrupt metabolic processes. Associations between sleep timing in nonshift workers and metabolic health are unknown. We examined sleep timing and indices of metabolic health in a community sample of midlife women. METHODS: Caucasian (n = 161), African American (n = 121) and Chinese (n = 56) non-shift-working women aged 48-58 y who were not taking insulin-related medications, participated in the Study of Women's Health Across the Nation (SWAN) Sleep Study and were subsequently examined approximately 5.39 (standard deviation = 0.71) y later. Daily diary-reported bedtimes were used to calculate four measures of sleep timing: mean bedtime, bedtime variability, bedtime delay and bedtime advance. Body mass index (BMI) and insulin resistance (homeostatic model assessment-insulin resistance, HOMA-IR) were measured at two time points. Linear regressions evaluated whether sleep timing was associated with BMI and HOMA-IR cross-sectionally and prospectively. RESULTS: In cross-sectional models, greater variability in bedtime and greater bedtime delay were associated with higher HOMA-IR (ß = 0.128; P = 0.007, and ß = 0.110; P = 0.013, respectively) and greater bedtime advance was associated with higher BMI (ß = 0.095; P = 0.047). Prospectively, greater bedtime delay predicted increased HOMA-IR at Time 2 (ß = 0.152; P = 0.003). Results were partially explained by shifted sleep timing on weekends. CONCLUSION: Frequent shifts in sleep timing may be related to metabolic health among non-shift working midlife women. COMMENTARY: A commentary on this article appears in this issue on page 269.

Inflammatory/hemostatic biomarkers and coronary artery calcification in midlife women of African-American and White race/ethnicity: the Study of Women's Health Across the Nation (SWAN) heart study.

OBJECTIVE: Inflammatory/hemostatic biomarkers are associated with coronary heart disease events, but relationships in asymptomatic midlife women are uncertain. We evaluated separately whether high-sensitivity C-reactive protein (hsCRP), fibrinogen, plasminogen-activator inhibitor 1, tissue plasminogen activator antigen, and circulating factor VII (factor VIIc) were associated with coronary artery calcification (CAC) in healthy midlife women. METHODS: A cross-sectional study was performed of participants from the Study of Women's Health Across the Nation. Logistic and Tobit regression was used to assess associations between log-transformed biomarkers, and CAC presence (CAC > 0) and extent. Effect modification by race/ethnicity was evaluated. RESULTS: The study included 372 women (mean age 51.3 y; 35.2% African-American). All biomarkers were positively associated with CAC presence and extent (P < 0.001 for all), adjusting for Framingham risk score, site, race/ethnicity, menopause status, income, and education. Additional adjustment for body mass index explained all associations except for factor VIIc, which remained associated with CAC extent only (P = 0.02). Final adjustment for insulin resistance, family history of cardiovascular disease, and cardiovascular medication use produced similar results. Associations between hsCRP, and CAC presence and extent were modified by race/ethnicity (P < 0.05). Log(hsCRP) was positively associated with CAC presence (odds ratio 3.25; 95% CI, 1.53-6.90; P = 0.002; per 1 log unit increase) and CAC extent (ß = 19.66; SE = 7.67; P = 0.01; per 1 log unit increase) in African-Americans only. CONCLUSIONS: Inflammatory/hemostatic biomarkers were associated with CAC through obesity, except for factor VIIc. Among African-American women only, hsCRP was independently associated with CAC, suggesting that hsCRP may have a role in coronary heart disease prevention in African-American midlife women.

Chronic Stress is Prospectively Associated with Sleep in Midlife Women: The SWAN Sleep Study.

STUDY OBJECTIVES: Evaluate whether levels of upsetting life events measured over a 9-y period prospectively predict subjective and objective sleep outcomes in midlife women. DESIGN: Prospective cohort study. SETTING: Four sites across the United States. PARTICIPANTS: 330 women (46-57 y of age) enrolled in the Study of Women's Health Across the Nation (SWAN) Sleep Study. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Upsetting life events were assessed annually for up to 9 y. Trajectory analysis applied to life events data quantitatively identified three distinct chronic stress groups: low stress, moderate stress, and high stress. Sleep was assessed by self-report and in-home polysomnography (PSG) during the ninth year of the study. Multivariate analyses tested the prospective association between chronic stress group and sleep, adjusting for race, baseline sleep complaints, marital status, body mass index, symptoms of depression, and acute life events at the time of the Sleep Study. Women characterized by high chronic stress had lower subjective sleep quality, were more likely to report insomnia, and exhibited increased PSG-assessed wake after sleep onset (WASO) relative to women with low to moderate chronic stress profiles. The effect of chronic stress group on WASO persisted in the subsample of participants without baseline sleep complaints. CONCLUSIONS: Chronic stress is prospectively associated with sleep disturbance in midlife women, even after adjusting for acute stressors at the time of the sleep study and other factors known to disrupt sleep. These results are consistent with current models of stress that emphasize the cumulative effect of stressors on health over time.

African Genetic Ancestry is Associated with Sleep Depth in Older African Americans.

STUDY OBJECTIVES: The mechanisms that underlie differences in sleep characteristics between European Americans (EA) and African Americans (AA) are not fully known. Although social and psychological processes that differ by race are possible mediators, the substantial heritability of sleep characteristics also suggests genetic underpinnings of race differences. We hypothesized that racial differences in sleep phenotypes would show an association with objectively measured individual genetic ancestry in AAs. DESIGN: Cross sectional. SETTING: Community-based study. PARTICIPANTS: Seventy AA adults (mean age 59.5 ± 6.7 y; 62% female) and 101 EAs (mean age 60.5 ± 7 y, 39% female). MEASUREMENTS AND RESULTS: Multivariate tests were used to compare the Pittsburgh Sleep Quality Index (PSQI) and in-home polysomnographic measures of sleep duration, sleep efficiency, apnea-hypopnea index (AHI), and indices of sleep depth including percent visually scored slow wave sleep (SWS) and delta EEG power of EAs and AAs. Sleep duration, efficiency, and sleep depth differed significantly by race. Individual % African ancestry (%AF) was measured in AA subjects using a panel of 1698 ancestry informative genetic markers and ranged from 10% to 88% (mean 67%). Hierarchical linear regression showed that higher %AF was associated with lower percent SWS in AAs (ß (standard error) = -4.6 (1.5); P = 0.002), and explained 11% of the variation in SWS after covariate adjustment. A similar association was observed for delta power. No association was observed for sleep duration and efficiency. CONCLUSION: African genetic ancestry is associated with indices of sleep depth in African Americans. Such an association suggests that part of the racial differences in slow-wave sleep may have genetic underpinnings.

Lipoprotein subclasses and endogenous sex hormones in women at midlife.

The objective of this work was to evaluate the associations between levels of endogenous sex hormones in women at midlife and lipoprotein subclasses. One hundred and twenty women (68 late peri-/postmenopausal and 52 pre-/early perimenopausal) from the Study of Women's Health Across the Nation (Pittsburgh site) were included. Lipoprotein subclasses were quantified using NMR spectroscopy. Participants (57.5% White and 42.5% Black) were 50.4 ± 1.9 years old. Adjusting for age, race, cycle day of blood draw, BMI, physical activity, and alcohol consumption, a negative correlation was found between estradiol (E2) and medium-small LDL particle (LDL-P) concentration (ρ = -0.19, P = 0.04). Further, E2 was positively correlated with HDL particle (HDL-P) size (ρ = 0.22, P = 0.02). For sex hormone binding globulin (SHBG), independent negative correlation was found with total small LDL-P concentration. SHBG was also positively correlated with LDL-P and HDL-P sizes (P < 0.05 for all). For free androgen index (FAI), positive correlations were found with concentrations of total VLDL particles, total LDL-Ps, and total small LDL-Ps. Additionally, FAI was negatively correlated with large HDL-P concentration, and HDL-P and LDL-P sizes (P < 0.05 for all). Lower levels of E2 and SHBG, and higher levels of FAI were associated with a more atherogenic profile of lipoprotein subclasses. Sex hormone levels at midlife may increase women's risk of coronary heart disease.

Utility of actiwatch sleep monitor to assess waking movement behavior in older women.

PURPOSE: Wrist-worn accelerometer devices measure sleep in free-living settings. Few studies, however, have investigated whether these devices can also measure waking movement behavior (e.g., total movement volume, physical activity). The purpose of this study was to investigate the ability of a wrist-worn Actiwatch 2 sleep monitor to rank total movement volume and physical activity levels compared with a waist-worn ActiGraph GT1M accelerometer and self-reported leisure time physical activity, respectively. In addition, we compared temporally matched activity measured via the ActiGraph GT1M and Actiwatch 2 over the study week. METHODS: A subset of women from the Healthy Women Study (n = 145; age, 73.3 ± 1.7 yr) wore an Actiwatch 2 on their nondominant wrist and an ActiGraph GT1M on their dominant hip for seven consecutive days. Participants recorded their leisure time physical activity in a 7-d diary and completed the past year version of the Modifiable Activity Questionnaire. Analyses were conducted for all wake periods and separately for active periods when both devices were worn. RESULTS: Spearman rank-order correlation coefficients for total movement volume between the Actiwatch 2 and ActiGraph GT1M were significant for wake periods (r = 0.47, P < 0.001) and, to a lesser extent, for active periods (r = 0.26, P < 0.01). However, the Actiwatch 2 did not rank participant's physical activity levels similarly to self-reported leisure time physical activity estimates (κ ≤ 0.05, P > 0.05). Multilevel model analyses comparing temporally matched activity measured via the ActiGraph GT1M and Actiwatch 2 suggest that the two devices yielded similar levels of activity during wake periods (B = 0.90; SE, 0.008; P < 0.001) and during active periods (B = 0.81; SE, 0.01; P < 0.001). CONCLUSIONS: A wrist-worn Actiwatch 2 may be useful for ranking total movement volume and for assessing the pattern of activity over a day in older women. However, our data do not support using a wrist-worn Actiwatch 2 device for measuring physical activity.