The independent associations of anti-Müllerian hormone and estradiol levels over the menopause transition with lipids/lipoproteins: The Study of Women's health Across the Nation.

BACKGROUND: The menopause transition (MT) is linked to adverse changes in lipids/lipoproteins. However, the related contributions of anti-Müllerian hormone (AMH) and estradiol (E2) are not clear. OBJECTIVE: To evaluate the independent associations of premenopausal AMH and E2 levels and their changes with lipids/lipoproteins levels [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1)] over the MT. METHODS: SWAN participants who transitioned to menopause without exogenous hormone use, hysterectomy, or bilateral oophorectomy with data available on both exposure and outcomes when they were premenopausal until the 1st visit postmenopausal were studied. RESULTS: The study included 1,440 women (baseline-age:mean±SD=47.4±2.6) with data available from up to 9 visits (1997-2013). Lower premenopausal levels and greater declines in AMH were independently associated with greater TC and HDL-C, whereas lower premenopausal levels and greater declines in E2 were independently associated with greater TG and apo B and lower HDL-C. Greater declines in AMH were independently associated with greater apoA-1, and greater declines in E2 were independently associated with greater TC and LDL-C. CONCLUSIONS: AMH and E2 and their changes over the MT relate differently to lipids/lipoproteins profile in women during midlife. Lower premenopausal and/or greater declines in E2 over the MT were associated with an atherogenic lipid/lipoprotein profile. On the other hand, lower premenopausal AMH and/or greater declines in AMH over the MT were linked to higher apo A-1 and HDL-C; the later found previously to be related to a greater atherosclerotic risk after menopause.

Early Life SES, Childhood Trauma Exposures, and Cardiovascular Responses to Daily Life Stressors in Middle-aged Adults.

BACKGROUND: Dysregulation in physiological responses to stress may provide a mechanism through which low socioeconomic status (SES) in childhood negatively impacts health. Evidence linking early life SES to physiological stress responses is inconsistent. Exposure to childhood trauma may be an important source of heterogeneity accounting for mixed findings. Guided by the adaptive calibration model, we examined whether childhood SES and childhood trauma jointly predict ambulatory measures of cardiovascular responses to daily life stressors. METHOD: A sample of 377 healthy, middle-aged adults (62% female, 80% White, 64% college-educated, Mage = 52.59 ± 7.16) completed a 4-day ecological momentary assessment protocol that measured task strain, social conflict, and ambulatory systolic and diastolic blood pressure (SBP and DBP, respectively) at hourly intervals throughout the day. Average ambulatory blood pressure responses to stress were calculated by regressing momentary SBP and DBP on momentary measures of stress within the multilevel models. Early life SES and childhood trauma were measured retrospectively by self-report questionnaire. RESULTS: Multilevel models controlling for momentary influences on blood pressure and age, sex, and race showed no main effects of early life SES or childhood trauma on ambulatory measures of cardiovascular responses to daily life stress. An interaction emerged for DBP responses to social conflict, where individuals raised in middle SES families who experienced trauma showed a blunted response relative to those who did not ([Formula: see text]-0.93, 95% CI: [-1.62, -0.24], p = .008). There was no significant SES-trauma interaction in predicting SBP responses to social conflict or blood pressure responses to task strain. CONCLUSION: Results do not provide support for our predictions that were derived from the adaptive calibration model, but do suggest that the impacts of early childhood experiences on cardiovascular responses may vary by type of daily stress experience.

Psychosocial impacts of the COVID-19 pandemic on women with trauma histories: Study of Women's Health Across the Nation (SWAN).

Older adults, particularly those with trauma histories, may be vulnerable to adverse psychosocial outcomes during the COVID-19 pandemic. We tested associations between prepandemic childhood abuse or intimate partner violence (IPV) and elevated depressive, anxiety, conflict, and sleep symptoms during the pandemic among aging women. Women (N = 582, age: 65-77 years) from three U.S. sites (Pittsburgh, Boston, Newark) of the longitudinal Study of Women's Health Across the Nation (SWAN) reported pandemic-related psychosocial impacts from June 2020-March 2021. Prepandemic childhood abuse; physical/emotional IPV; social functioning; physical comorbidities; and depressive, anxiety, and sleep symptoms were drawn from SWAN assessments between 2009 and 2017. There were no measures of prepandemic conflict. In total, 47.7% and 35.3% of women, respectively, reported childhood abuse or IPV. Using logistic regression models adjusted for age; race/ethnicity; education; site; prepandemic social functioning and physical comorbidities; and, in respective models, prepandemic depressive, anxiety, or sleep symptoms, childhood abuse predicted elevated anxiety symptoms, OR = 1.67, 95% CI [1.10, 2.54]; household conflict, OR = 2.19, 95% CI [1.32, 3.61]; and nonhousehold family conflict, OR = 2.14, 95% CI [1.29, 3.55]. IPV predicted elevated sleep problems, OR = 1.63, 95% CI [1.07, 2.46], and household conflict, OR = 1.96, 95% CI [1.20, 3.21]. No associations emerged for depressive symptoms after adjusting for prepandemic depression. Aging women with interpersonal trauma histories reported worse anxiety, sleep, and conflict during the COVID-19 pandemic than those without. Women's trauma histories and prepandemic symptoms are critical to understanding the psychosocial impacts of the pandemic.

Systemic Inflammation Contributes to the Association Between Childhood Socioeconomic Disadvantage and Midlife Cardiometabolic Risk.

BACKGROUND: Childhood socioeconomic disadvantage is associated with increased risk for chronic inflammation and cardiometabolic disease at midlife. PURPOSE: As it is presently unknown whether inflammation mediates the relationship between childhood socioeconomic status (SES) and adulthood cardiometabolic risk, we investigated associations between retrospectively reported childhood SES, circulating levels of inflammatory markers, and a latent construct of cardiometabolic risk in midlife adults. METHODS: Participants were 1,359 healthy adults aged 30-54 (Adult Health and Behavior Iⅈ 52% women, 17% Black) who retrospectively reported childhood SES (parental education, occupational grade). Measures included plasma interleukin (IL)-6, C-reactive protein (CRP), and cardiometabolic risk factors. Structural equation modeling was conducted, with cardiometabolic risk modeled as a second-order latent variable with adiposity, blood lipids, glucose control, and blood pressure as first-order components. RESULTS: Lower childhood SES was associated with greater risk for cardiometabolic disease at midlife (ß = -0.08, CI[-0.04, -0.01], p = .01) in models adjusted for demographics, but this association was attenuated in models that adjusted for adulthood SES and health behaviors. In fully-adjusted models, the relationship between lower childhood SES and adult cardiometabolic risk was partially explained by higher circulating levels of CRP (ß = -0.05, CI[-0.02, -0.01], p = .001), but not by IL-6. In an exploratory model, lower adulthood SES was also found to independently contribute to the association between childhood SES and adult cardiometabolic risk (ß = -0.02, CI[-0.01, -0.001], p = .02). CONCLUSIONS: The current study provides initial evidence that systemic inflammation may contribute to childhood socioeconomic disparities in cardiometabolic risk in midlife. Future work would benefit from prospective investigation of these relationships.

Early Midlife Cardiovascular Health Influences Future HDL Metrics in Women: The SWAN HDL Study.

Background Utility of high-density lipoprotein cholesterol (HDL-C) in assessing the antiatherogenic properties of HDL may be limited in midlife women. Novel metrics of HDL function, lipid contents, and subclasses may better reflect the atheroprotective capacities of HDL, supporting the need to evaluate how cardiovascular health affects these metrics in women. We assessed the relationship of early midlife Life's Simple 7 (LS7) score and its health behavior components with future HDL function (HDL-cholesterol efflux capacity), HDL-phospholipid, HDL-triglyceride, HDL particles (HDL-P) and size, and the relationship between LS7 score and changes in HDL metrics over time. Methods and Results We analyzed 529 women (baseline age: 46.4 [2.6] years, 57% White) from the SWAN HDL (Study of Women's Health Across the Nation HDL) study who had baseline LS7 followed by future repeated HDL metrics. Multivariable linear mixed models were used. Higher LS7 score was associated with favorable future HDL profile (higher HDL-phospholipid, total HDL-P and large HDL-P, lower HDL-triglyceride, and larger overall HDL size). Ideal body mass index was associated with higher HDL-cholesterol efflux capacity, HDL-phospholipid, and large HDL-P, lower HDL-triglyceride and small HDL-P, and larger overall HDL size. Ideal physical activity was associated with higher HDL-phospholipid, and total, large, and medium HDL-P. Ideal smoking was associated with less HDL-triglycerides. Diet was not related to HDL metrics. Higher LS7 score and ideal body mass index were associated with slower progression of HDL size over time. Conclusions Novel HDL metrics may better reflect the clinical utility of HDL. Improving lifestyle at midlife, particularly maintaining ideal body mass index, is associated with better future HDL phenotype.

Blood Pressure Cuff Inflation Briefly Increases Female Adolescents' Restlessness During Sleep on the First But Not Second Night of Ambulatory Blood Pressure Monitoring.

OBJECTIVE: Ambulatory blood pressure monitoring (ABPM) increases restlessness during adults' sleep in laboratory settings, but there is little evidence of an association among adolescents or in naturalistic environments. This study examined activity levels before and after blood pressure cuff inflation during sleep to determine whether and for how long ABPM increased restlessness during sleep in healthy adolescents. METHODS: Two hundred thirty-four healthy adolescents (mean age = 15.72 [1.30] years; 54% female; 57% Black) completed two consecutive nights of hourly ABPM and wrist-worn actigraphy. Activity counts during sleep, averaged across 5-minute bins, were compared in the 20 minutes before and after blood pressure cuff inflation using a four-level mixed model (bins within hours within nights within participants). Interactions of bin with night, sex, and race were examined. Covariates included age, sex, and race. RESULTS: Activity counts in the 5-minute bin immediately after cuff inflation were 10% to 14% higher than all other bins before ( p < .001) and after ( p < .001) cuff inflation. This effect differed by night and sex, as activity levels during 5-minute post-cuff inflation were elevated only on night 1 ( p values < .001) and only in female participants ( p values < .001). Effects did not differ by race. CONCLUSIONS: Cuff inflation during ABPM briefly increased adolescent female participants' restlessness during sleep. Habituation occurred after one night, so two nights of ABPM may minimize impact on sleep. If only one night of ABPM is feasible, excluding 5 minutes of actigraphy data after each cuff inflation may accommodate the impact of ABPM on restlessness during sleep.

Interpersonal Trauma and Risk of Incident Cardiovascular Disease Events Among Women.

Background Traumatic experiences have been linked to risk for cardiovascular disease (CVD). Interpersonal violence is a trauma that is prevalent in women. Among midlife women followed up for 2 decades, we examined whether interpersonal violence (childhood abuse, adulthood abuse, or intimate partner violence [IPV]) was related to increased risk of subsequent clinical CVD events. Methods and Results A total of 2201 women, aged 42 to 52 years at baseline, underwent up to 16 in-person visits over 22 years. Measures included questionnaires (including of childhood physical/sexual abuse, adult physical/sexual abuse, and IPV), physical measures, phlebotomy, and reported CVD events (myocardial infarction, stroke, heart failure, and revascularization). Death certificates were collected. Relationships between childhood abuse, adult abuse, and IPV with incident fatal/nonfatal CVD were tested in Cox proportional hazards models. Women with a childhood abuse history had increased risk for incident CVD (versus no abuse; hazard ratio [HR] [95% CI], 1.65 [1.12-2.44]; P=0.01; adjusted for demographics and CVD risk factors); associations were strongest for childhood sexual abuse. Adult abuse was not significantly associated with CVD. Women with IPV had a doubling of risk for incident CVD in demographic-adjusted models (versus no IPV; IPV: HR [95% CI], 2.06 [1.01-4.23]; P=0.04; no partner: HR [95% CI], 1.79 [0.91-3.53]; P=0.09); systolic blood pressure partially mediated relationships between IPV and CVD. Conclusions Childhood abuse, particularly sexual abuse, was associated with increased risk of CVD in women. IPV was associated with risk for CVD, with the higher systolic blood pressure among IPV-exposed women important in these associations. Interpersonal violence prevention may contribute to CVD risk reduction in women.

Comparing polysomnography, actigraphy, and sleep diary in the home environment: The Study of Women's Health Across the Nation (SWAN) Sleep Study.

Study Objectives: Polysomnography (PSG) is considered the "gold standard" for assessing sleep, but cost and burden limit its use. Although wrist actigraphy and self-report diaries are feasible alternatives to PSG, few studies have compared all three modalities concurrently across multiple nights in the home to assess their relative validity across multiple sleep outcomes. This study compared sleep duration and continuity measured by PSG, actigraphy, and sleep diaries and examined moderation by race/ethnicity. Methods: Participants from the Study of Women's Health Across the Nation (SWAN) Sleep Study included 323 White (n = 147), African American (n = 120), and Chinese (n = 56) middle-aged community-dwelling women (mean age: 51 years, range: 48-57). PSG, wrist actigraphy (AW-64; Philips Respironics, McMurray, PA), and sleep diaries were collected concurrently in participants' homes over three consecutive nights. Multivariable repeated-measures linear models compared time in bed (TIB), total sleep time (TST), sleep efficiency (SE), sleep latency (SL), and wake after sleep onset (WASO) across modalities. Results: Actigraphy and PSG produced similar estimates of sleep duration and efficiency. Diaries yielded higher estimates of TIB, TST, and SE versus PSG and actigraphy, and lower estimates of SL and WASO versus PSG. Diary SL was shorter than PSG SL only among White women, and diary WASO was lower than PSG and actigraphy WASO among African American versus White women. Conclusions: Given concordance with PSG, actigraphy may be preferred as an alternative to PSG for measuring sleep in the home. Future research should consider racial/ethnic differences in diary-reported sleep continuity.

Psychosocial Well-Being and Progression of Coronary Artery Calcification in Midlife Women.

Background Prevention of cardiovascular disease (CVD) is a public health priority. The combination of physical activity, a healthy diet, and abstaining from tobacco plays an important role in prevention whereas aspects of psychosocial well-being have largely been examined separately with conflicting results. This study evaluated whether the combination of indices of psychosocial well-being was associated with less progression of coronary artery calcium (CAC). Methods and Results Participants were 312 women (mean age 50.8) from the SWAN (Study of Women's Health Across the Nation) ancillary Heart Study, free of clinical CVD at baseline. A composite psychosocial well-being score was created from 6 validated psychosocial questionnaires assessing optimism, vitality, life engagement, life satisfaction, rewarding multiple roles, and positive affect. Subclinical CAC progression was defined as an increase of ≥10 Agatston units over 2.3 years measured using electron beam tomography. Relative risk (RR) regression models examined the effect of well-being on CAC progression, progressively adjusting for sociodemographic factors, depression, healthy lifestyle behaviors, and standard CVD risk factors. At baseline, 42.9% had a CAC score >0, and progression was observed in 17.6%. Well-being was associated with less progression (RR, 0.909; 95% CI, 0.843-0.979; P=0.012), which remained significant with adjustment for potential confounders, depression, and health behaviors. Further adjustment for standard CVD risk factors weakened the association for the total sample (RR, 0.943; 95% CI, 0.871-1.020; P=0.142) but remained significant for the 134 women with baseline CAC>0 (RR, 0.921; 95% CI, 0.852-0.995; P=0.037). Conclusions Optimum early prevention of CVD in women may result from including the mind side of the mind-heart-body continuum.

Adiposity and Smoking Mediate the Relationship Between Depression History and Inflammation Among Young Adults.

BACKGROUND: Depression is associated with inflammation, but the mechanisms underlying this association are unclear. We examined adiposity and smoking as potential pathways through which childhood depression may lead to an elevated inflammatory status among young adults. METHODS: The sample included 294 subjects with histories of depression (probands), 270 never-depressed siblings of probands (high-risk siblings), and 169 controls. C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM-1) were assessed in serum samples. An adiposity score was computed from body mass index and waist circumference. Smoking behavior was evaluated during an interview. Mixed-effects models were used to test whether adiposity and smoking mediate the relationship between depression and inflammation. RESULTS: Probands (p = .004), but not siblings (p = .071), had higher levels of sICAM-1 compared to controls. However, depression history and risk status had no direct effects on CRP (ps > .13) or IL-6 (ps > .16). Importantly, adiposity indirectly mediated the effect of group (probands vs. controls; siblings vs. controls) on all three inflammatory markers. Smoking indirectly mediated the effect of group (probands vs. controls; siblings vs. controls) on sICAM-1 only. CONCLUSIONS: Among young adults, the adverse inflammatory consequences of depression history are significant for sICAM-1. Adiposity and smoking are pathways through which depression can indirectly impact several inflammatory markers, suggesting possible preventive interventions to improve the immunologic and cardiovascular health of depression-prone individuals.

Trajectories of Blood Pressure in Midlife Women: Does Menopause Matter?

BACKGROUND: Whether changes in blood pressure (BP) over women's midlife are more driven by chronological aging or the menopause transition has been debated. We sought to determine whether women can be classified into distinct trajectory groups based on pattern and level of systolic BP (SBP), diastolic BP, pulse pressure (PP), and mean arterial pressure (MAP) over the menopause transition, and to assess whether menopause-related factors predict the group and level of BP measures. METHODS: Participants were from the SWAN (Study of Women's Health Across the Nation). Group-based trajectory modeling was used to identify women who shared distinct BP trajectories over time relative to menopause onset and to assess associations of menopause-related factors with trajectory group and level of BP measures. An accelerated rise relative to menopause onset suggests a menopause contribution. RESULTS: The study included 3302 multiracial and multiethnic women with BP measures over 17 follow-up visits (baseline age [SD]: 46.3 [2.7]). Women were classified into either low, medium, or high trajectory group in each BP measure. The low SBP, PP, and MAP trajectories (in 35%, 53%, and 28% of the cohort, respectively) were rising slowly before menopause but showed a significant accelerated rise 1 year after menopause, indicating a menopause contribution. The remaining BP trajectories were rising up until menopause and either continued with the same rise or declined after menopause. A younger menopause age predicted the low SBP, PP, and MAP trajectories. A greater follicle-stimulating hormone level predicted lower SBP and PP levels, while vasomotor symptoms occurrence predicted higher SBP, PP, and MAP levels over time. Estradiol did not predict trajectory or level of any BP measure. CONCLUSIONS: Distinct BP trajectories over the menopause transition exist that revealed a group of women whose SBP, PP, and MAP trajectories are consistent with a menopause contribution. Our findings support frequent monitoring of BP during the menopause transition.

Age Trends in Actigraphy and Self-Report Sleep Across the Life Span: Findings From the Pittsburgh Lifespan Sleep Databank.

OBJECTIVE: Sleep changes over the human life span, and it does so across multiple dimensions. We used individual-level cross-sectional data to characterize age trends and sex differences in actigraphy and self-report sleep dimensions across the healthy human life span. METHODS: The Pittsburgh Lifespan Sleep Databank consists of harmonized participant-level data from sleep-related studies conducted at the University of Pittsburgh (2003-2019). We included data from 1065 (n = 577 female; 21 studies) Pittsburgh Lifespan Sleep Databank participants aged 10 to 87 years without a major psychiatric, sleep, or medical condition. All participants completed wrist actigraphy and the self-rated Pittsburgh Sleep Quality Index. Main outcomes included actigraphy and self-report sleep duration, efficiency, and onset/offset timing, and actigraphy variability in midsleep timing. RESULTS: We used generalized additive models to examine potentially nonlinear relationships between age and sleep characteristics and to examine sex differences. Actigraphy and self-report sleep onset time shifted later between ages 10 and 18 years (23:03-24:10 [actigraphy]; 21:58-23:53 [self-report]) and then earlier during the 20s (00:08-23:40 [actigraphy]; 23:50-23:34 [self-report]). Actigraphy and self-report wake-up time also shifted earlier during the mid-20s through late 30s (07:48-06:52 [actigraphy]; 07:40-06:41 [self-report]). Self-report, but not actigraphy, sleep duration declined between ages 10 and 20 years (09:09-07:35). Self-report sleep efficiency decreased over the entire life span (96.12-93.28), as did actigraphy variability (01:54-01:31). CONCLUSIONS: Awareness of age trends in multiple sleep dimensions in healthy individuals-and explicating the timing and nature of sex differences in age-related change-can suggest periods of sleep-related risk or resilience and guide intervention efforts.

Associations of Endogenous Hormones With HDL Novel Metrics Across the Menopause Transition: The SWAN HDL Study.

CONTEXT: Novel metrics of high-density lipoprotein (HDL) (subclasses, lipid content, and function) may improve characterization of the anti-atherogenic features of HDL. In midlife women, changes in these metrics vary by time relative to the final menstrual period (FMP), supporting a contribution of estradiol (E2) and follicle-stimulating hormone (FSH). OBJECTIVE: We tested associations of endogenous E2 and FSH with novel HDL metrics and assessed whether these associations varied by time relative to FMP. METHODS: This study was a longitudinal analysis from the Study of Women's Health Across the Nation (SWAN) HDL study, using a community-based cohort of 463 women, baseline mean age 50.2 (2.7) years. The main outcome measures were HDL cholesterol efflux capacity (HDL-CEC), HDL phospholipids (HDL-PL), HDL triglycerides (HDL-Tg), HDL particles (HDL-P), HDL size, and HDL cholesterol (HDL-C). RESULTS: In multivariable analyses, E2 was positively associated with HDL size, large HDL-P, HDL-CEC, and HDL-Tg, but negatively with medium HDL-P (P values < 0.05). The positive association between E2 and HDL-Tg was stronger 2 years post-FMP than before, (interaction P = 0.031). FSH was positively related to total and medium HDL-P, but negatively to HDL size, large HDL-P, and HDL-CEC per particle (P values < 0.05). Associations of higher FSH with greater total HDL-P and smaller HDL size were only evident at/after menopause (interaction P values < 0.05). CONCLUSION: Some of the associations linking E2 and FSH with novel HDL metrics were vulnerable to time relative to menopause onset. Whether a late initiation of hormone therapy relative to menopause could have a detrimental effect on lipid content of HDL particles should be tested in the future.

The Cardiovascular Cost of Silence: Relationships Between Self-silencing and Carotid Atherosclerosis in Midlife Women.

BACKGROUND: Individuals engage in a range of behaviors to maintain close relationships. One behavior is self-silencing or inhibiting self-expression to avoid relationship conflict or loss. Self-silencing is related to poor mental health and self-reported physical health in women but has not been examined in relation to cardiovascular health, particularly using direct measures of the vasculature. PURPOSE: To test associations between self-silencing and carotid atherosclerosis in midlife women; secondary analyses examined moderation by race/ethnicity. METHODS: Women (N = 290, ages 40-60) reported on self-silencing in intimate relationships and underwent physical measurements, blood draw, and ultrasound assessment of carotid intima-media thickness (IMT) and plaque. Associations between self-silencing and mean IMT and plaque index (0, 1, ≥2) were tested in linear regression and multinomial logistic regression models, respectively, followed by interaction terms between self-silencing and race, adjusted for demographic factors, CVD risk factors, partner status, depression, physical activity, and diet. RESULTS: Forty-seven percent of women demonstrated carotid plaque. Greater self-silencing was related to increased odds of plaque index ≥2 (e.g., for each additional point, odds ratio [95% confidence interval] = 1.16 [1.03-1.31], p = .012), relative to no plaque). Moderation analyses indicated that self-silencing was related to odds of plaque index ≥2 in non-white women (1.15 [1.05-1.26], p = .004), but there was no significant relationship in white women (1.01 [0.97-1.06], p = .550). No associations emerged for IMT. CONCLUSIONS: Among midlife women, self-silencing was associated with carotid plaque, independent of CVD risk factors, depression, and health behaviors. Emotional expression in relationships may be important for women's cardiovascular health.

Does childhood maltreatment or current stress contribute to increased risk for major depression during the menopause transition?

BACKGROUND: The menopausal transition (MT) poses an increased risk for major depression (MD), but not for all women. Current and past stress are toxic risk factors for depression throughout life. The MT may be a time of increased sensitivity to stress, especially among women with a lifetime history of major depressive disorder (MDD). We evaluated whether women who experienced childhood maltreatment (CM) or current stressful events or ongoing problems were at increased risk for MD during the MT. METHODS: At the Pittsburgh site of the Study of Women's Health Across the Nation, 333 midlife women were interviewed approximately annually over 15 years with the Structured Clinical Interview for the Diagnosis of DSM-IV Axis I Disorders and provided health and psychosocial data including the Childhood Trauma Questionnaire. Repeated measures logistic regression analyses were conducted separately for women with and without lifetime MDD at study entry. RESULTS: Among women with lifetime MDD, CM, but not current stress, interacted with menopausal status to increase the risk for MD during postmenopause (ORs ranged from 2.71 to 8.04). All stressors were associated with increased odds of MD. Among women without lifetime MDD, current stress was related to risk for MD, but the effect did not vary by menopausal status. CONCLUSIONS: Women with MDD prior to midlife and who experienced CM were at greatest risk for MD after the MT. Women without prior MDD were at increased risk for MD during peri- and postmenopause. Healthcare providers should monitor women at risk for MD even after the MT.

Age at Menopause in Relationship to Lipid Changes and Subclinical Carotid Disease Across 20 Years: Study of Women's Health Across the Nation.

Background Younger age at final menstrual period (FMP) is associated with increased risk for cardiovascular disease events. This paper evaluated whether older age at FMP is associated with more favorable patterns of lipid changes during the menopause transition and whether these changes are associated with less subclinical carotid disease in the postmenopausal years. Methods and Results Lipids and lipoproteins were measured repeatedly among 1554 premenopausal women who had a natural menopause during follow-up years (median=18.8 years); a subset of 890 women also had measures of carotid intima media thickness, adventitial diameter, and plaque. Women who had an older FMP age had less adverse changes in cholesterol from 1 to 3 years after FMP, and in triglycerides from FMP to 3 years after FMP, but they had more adverse changes in ApoB and Apo A1 from 3 years before to 1 year after the FMP. Increasing cholesterol and ApoB from 1 to 3 years after FMP were associated with greater intima media thickness and adventitial diameter, and the greater likelihood of a plaque score >2 the older the age at FMP. Conclusions Despite the epidemiological literature showing early age at FMP is associated with elevated risk for cardiovascular disease events, older age at FMP had inconsistent associations with less adverse lipid changes in midlife, which did not translate into less risk for subclinical carotid disease and in some cases more risk. These findings are restricted to women who experience FMP in the normative age range for the menopausal transition.

Associations of HDL metrics with coronary artery calcium score and density among women traversing menopause.

The cardioprotective association of high-density lipoprotein cholesterol (HDL-C) may vary by menopause stage or estradiol level. We tested whether associations of comprehensive HDL metrics (HDL subclasses, phospholipid and triglyceride content, and HDL cholesterol efflux capacity [HDL-CEC]) with coronary artery calcium (CAC) score and density vary by menopause stage or estradiol level in women transitioning through menopause. Participants (N = 294; mean age [SD]: 51.3 [2.9]) had data on HDL metrics and CAC measures at one or two time points during the menopause transition. Generalized estimating equations were used for analyses. Effect modifications by menopause stage or estradiol level were tested in multivariable models. In adjusted models, menopause stage modified the associations of specific HDL metrics with CAC measures. Higher small HDL particles (HDL-P) concentrations (p-interaction = 0.008) and smaller HDL size (p-interaction = 0.02) were associated with greater odds of CAC presence in late perimenopause than in pre/early perimenopause stage. Women in the highest estradiol tertile, but not the lower tertiles, showed a protective association of small HDL-P with CAC presence (p-interaction = 0.007). Lower large HDL-P concentrations (p-interaction = 0.03) and smaller HDL size (p-interaction = 0.03) were associated with lower CAC density in late perimenopause than in postmenopause stage. Associations of HDL phospholipid and triglyceride content and HDL-CEC with CAC measures did not vary by menopause stage or estradiol level. We concluded that HDL subclasses may impact the likelihood of CAC presence and the stability of coronary plaque differently over the menopause transition. Endogenous estradiol levels may contribute to this observation.

Childhood-onset depression and arterial stiffness in young adulthood.

OBJECTIVES: The literature on childhood-onset depression and future compromised vascular function is suggestive but limited. The objective of this study was to determine if arterial stiffness, a predictor of future cardiovascular disease (CVD), measured in young adulthood, is associated with childhood-onset depression. METHODS: Cardiometabolic risk factors and pulse wave velocity (PWV), a measure of arterial stiffness, were cross-sectionally assessed in young adults with a history of childhood-onset depression (clinical diagnosis of major depressive episode or dysthymic disorder; N = 294 probands; initially recruited via child mental health facilities across Hungary; mean age of first depressive episode = 10.4 years), their never-depressed full biological siblings (N = 269), and never-depressed controls (N = 169). The mean ages of probands, siblings, and controls at the PWV visit were 25.6, 25.0, and 21.7 years, respectively, and 8.8% of the probands were in a current depressive episode. RESULTS: Controlling for age, sex, age*sex, education, and family clusters, PWV (m/s) did not statistically differ across the groups (probands = 7.01; siblings = 6.98; controls = 6.81). However, after adjusting for key covariates, there were several across-group differences in CVD risk factors: compared to controls, probands and siblings had higher diastolic blood pressure and lower high-density lipoprotein cholesterol, probands had higher triglycerides, and siblings had higher body mass index (all p < 0.05). CONCLUSION: We found limited evidence of an association between a history of childhood-onset depression and young adulthood arterial stiffness. However, our findings of elevated cardiovascular risk factors in those with childhood-onset depression suggest that pediatric depression may predispose to increased CVD risk later in life and warrants further investigation.

Influence of the menopausal transition on polysomnographic sleep characteristics: a longitudinal analysis.

STUDY OBJECTIVES: To evaluate how change in menopausal status related to spectral analysis and polysomnographic measures of sleep characteristics. METHODS: The Study of Women's Health Across the Nation (SWAN) Ancillary Sleep Study evaluated sleep characteristics of 159 women who were initially pre- or early perimenopausal and repeated the assessment about 3½ years later when 38 were pre- or early perimenopausal, 31 late perimenopausal, and 90 postmenopausal. Participants underwent in-home ambulatory polysomnography for two to three nights. Average EEG power in the delta and beta frequency bands was calculated during NREM and REM sleep, and sleep duration, wake after sleep onset (WASO), and apnea hypopnea index (AHI) were based on visually-scored sleep. RESULTS: The women who transitioned to postmenopause had increased beta NREM EEG power at the second assessment, compared to women who remained pre-or early premenopausal; no other sleep measures varied by change in menopausal status. In multivariate models the associations remained; statistical controls for self-reported hot flashes did not explain findings. In secondary analysis, NREM beta power at the second assessment was greater among women who transitioned into the postmenopause after adjustments for initial NREM beta power. CONCLUSIONS: Sleep duration and WASO did not vary by menopause transition group across assessments. Consistent with prior cross-sectional analysis, elevated beta EEG power in NREM sleep was apparent among women who transitioned to postmenopause, suggesting that independent of self-reported hot flashes, the menopausal transition is associated with physiological hyperarousal during sleep.

Pathways connecting family socioeconomic status in adolescence and sleep continuity in adult Black and White men.

OBJECTIVE: To evaluate the roles of parenting and adolescent characteristics during ages 13 to 16 in connecting family socioeconomic status (SES) during adolescence with adult sleep in Black and White men. DESIGN: Longitudinal school-based community study beginning in 1987-1988 when participants were enrolled in the first or seventh grade. SETTING: Pittsburgh, PA. PARTICIPANTS: 291 men (54.4% Black, mean age = 33, SD = 2.5) participated in 2012-2014 in a week-long study of sleep measured by actigraphy and diary. MEASURES: In adolescence (ages 13-16), measures of family SES based on occupation, education, income and public assistance; parenting based on monitoring, positive expectations for future, warm parent-child relationship, and communication; and adolescent characteristics based on anxiety, hyperactivity/impulsivity, and peer rejection.  In adulthood, participant SES, minutes awake after sleep onset (WASO), duration, and diary-assessed sleep quality. RESULTS: Structural equation modeling confirmed significant indirect pathways: (1) low family SES in adolescence to negative parenting to low adult SES to greater WASO; (2) low family SES in adolescence to adolescent characteristics to low adult SES to greater WASO; (3) Black race to low family SES in adolescence to negative parenting to low adult SES to greater WASO; and (4) Black race to low family SES in adolescence to adolescent characteristics to adult SES to greater WASO. Similar models for duration and quality were not confirmed. CONCLUSIONS: Parenting and adolescent characteristics may have an indirect association with adult sleep continuity. Parenting and mental health interventions in adolescence may improve adult sleep.