Objective
Most midlife women report vasomotor symptoms, yet their physiology remains poorly understood. This study tested whether acute decreases in cardiac vagal control would occur with vasomotor symptoms in a large sample of women monitored during wake and sleep.

Methods
215 nonsmoking women ages 40–60 with evidence of vasomotor symptoms were included. Women were free of a history of clinical cardiovascular disease or arrhythmia; or use of insulin, beta blockers, calcium channel blockers, or medications impacting vasomotor symptoms. Women underwent 24 hours of ambulatory monitoring for physiological (sternal skin conductance) and self-report (electronic diary) measurement of vasomotor symptoms; heart rate variability (electrocardiogram); and respiratory rate. Changes in cardiac vagal control as assessed by respiratory sinus arrhythmia during vasomotor symptoms relative to periods preceding and following vasomotor symptoms were tested in linear mixed models.

Results
Significant decreases in respiratory sinus arrhythmia were observed during physiologically-measured vasomotor symptoms relative to periods preceding (b(SE)=.13(.004), p<.0001) and following the VMS (b(SE)=.13(.004), p<.0001), adjusted for age, race, body mass index, sleep/wake. Decreases were observed for women not aware of their vasomotor symptoms, and persisted controlling for respiration rate. Interactions indicated that respiratory sinus arrhythmia decreases were most pronounced during sleep and for younger women.

Conclusions
Physiologically-measured vasomotor symptoms were accompanied by an inhibition of cardiac vagal control in a large sample of women. Changes were observed irrespective of whether the vasomotor symptoms were reported, were most pronounced during sleep, and were greatest among younger women. These findings contribute to the understanding of vasomotor symptom physiology.

Objective
A childhood history of abuse or neglect may be associated with elevated adult cardiovascular disease (CVD) risk. No studies have examined associations between child abuse/neglect and subclinical CVD using a validated measure of abuse and neglect. We hypothesized that midlife women with a childhood abuse or neglect history would have increased subclinical CVD beyond standard CVD risk factors. We tested moderation of associations by sleep, hot flashes, and race/ethnicity.

Methods
295 midlife women completed the Child Trauma Questionnaire, physiologic hot flash and actigraphic sleep monitoring, blood draw, and carotid ultrasound (intima media thickness, IMT; plaque). Relations between abuse/neglect and outcomes were tested in linear regression models adjusting for demographic, psychosocial, and CVD risk factors. Interactions with sleep, hot flashes, and race/ethnicity were tested.

Results
45% of women reported a history of child abuse or neglect. Women with any child abuse or neglect had higher IMT [b(SE)=.039(.011), p<.01] and carotid plaque [OR(95%CI= 1.95 (1.15–3.33), p<.05] than non-abused/neglected women. Further, physical abuse, emotional abuse, or emotional neglect were associated with higher subclinical CVD. Sexual abuse was associated with higher IMT among nonwhite women. Interactions with sleep time and sleep hot flashes (p values <.05) indicated that higher subclinical CVD with an abuse/neglect history was observed primarily among women sleeping <6 hours/night or with sleep hot flashes.

Conclusions
A history of child abuse or neglect is associated with higher subclinical CVD in women, particularly when paired with short sleep or hot flashes. Findings underscore the importance of childhood adversity in midlife women’s CVD risk.

Midlife, which encompasses the menopause transition in women, can be a time of disrupted sleep and accelerated atherosclerosis accumulation. Short or poor sleep quality has been associated with cardiovascular disease (CVD) risk; few studies have investigated relations among midlife women. We tested whether shorter actigraphy sleep time or poorer subjective sleep quality was associated with carotid atherosclerosis among midlife women.Two hundred fifty-six peri- and postmenopausal women aged 40–60 years completed 3 days of wrist actigraphy, hot flash monitoring, questionnaires (Pittsburgh Sleep Quality Index [PSQI], Berlin), a blood draw, and carotid ultrasound [intima media thickness (IMT), plaque]. Associations of objective (actigraphy) and subjective (PSQI) sleep with IMT/plaque were tested in regression models (covariates: age, race, education, body mass index, blood pressure, lipids, insulin resistance, medications, snoring, depressive symptoms, sleep hot flashes, and estradiol).Shorter objective sleep time was associated with higher odds of carotid plaque (for each hour shorter sleep, plaque score ≥ 2, odds ratio (OR) [95% confidence interval, CI] = 1.58 [1.11–2.27], p = .01; plaque score = 1, OR [95% CI] = 0.95 [0.68–1.32], p = .75, vs. no plaque, multivariable). Poorer subjective sleep quality was associated with higher mean IMT [β, b (standard error, SE) = 0.004 (0.002), p = .03], maximal IMT [b (SE) = 0.009 (0.003), p = .005], and plaque [plaque score ≥ 2, OR (95% CI) = 1.23 (1.09–1.40), p = .001; score = 1, OR (95% CI) = 1.06 (0.93–1.21), p = .37, vs. no plaque] in multivariable models. Findings persisted additionally adjusting for sleep hot flashes and estradiol.Shorter actigraphy-assessed sleep time and poorer subjective sleep quality were associated with increased carotid atherosclerosis among midlife women. Associations persisted adjusting for CVD risk factors, hot flashes, and estradiol.

Research suggests that sleep disturbances are associated with elevated levels of inflammation. Some evidence indicates that women may be particularly vulnerable; increased levels of inflammatory biomarkers with sleep disturbances are primarily observed among women. Midlife, which encompasses the menopause transition, is typically reported as a time of poor sleep. We tested whether poorer objectively measured sleep characteristics were related to a poorer inflammatory profile in midlife women.Two hundred ninety-five peri- and postmenopausal women aged 40–60 completed 3 days of wrist actigraphy, physiologic hot flash monitoring, questionnaires (e.g. Berlin sleep apnea risk questionnaire], and a blood draw for the assessment of inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and von Willebrand factor (VWF) antigen. Associations of objective (actigraphy) sleep with inflammatory markers were tested in regression models. Sleep efficiency was inverse log transformed. Covariates included age, race/ethnicity, education, body mass index, sleep apnea risk, homeostatic model assessment (a measure of insulin resistance), systolic blood pressure, low-density lipoprotein cholesterol, and physical activity.In separate models controlling for age, race/ethnicity, and education, lower sleep efficiency was associated with higher IL-6 [b(SE) = .02 (.10), p = .003] and VWF [b(SE) = .02 (.08), p = .002]. More minutes awake after sleep onset was associated with higher VWF [b(SE) = .12 (.06), p = .01]. Findings persisted in multivariable models.Lower sleep efficiency and more minutes awake after sleep onset were independently associated with higher circulating levels of VWF. Lower sleep efficiency was associated with higher circulating levels of IL-6. These findings suggest that sleep disturbances are associated with greater circulating inflammation in 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
272 nonsmoking women reporting either daily hot flashes or no hot flashes, aged 40-60, 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<.05) indicated that among the younger tertile of women in the sample (ages 40-53), the presence of hot flashes [beta(standard error)=-2.07 (.79), p=.01], and more frequent physiologic hot flashes were associated with lower flow mediated dilation [for each hot flash: beta(standard error)=-.10(.05), p=.03, multivariable]. Associations were not accounted for by estradiol. Associations were not observed among the older women (ages 54-60) or for prospective-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.

Traumatic experiences are common and linked to cardiovascular disease (CVD) risk, yet the mechanisms underlying these relationships is less well understood. Few studies have examined trauma exposure and its relation to autonomic influence over cardiac function, a potential pathway linking trauma exposure to CVD risk. Investigating autonomic influence over cardiac function during both wake and sleep is critical, given particular links of sleep autonomic function to cardiovascular health. Among midlife women, we tested whether trauma exposure would be related to lower high frequency heart rate variability (HF-HRV), an index of vagal influence over cardiac function, during wake and sleep. Three hundred and one nonsmoking midlife women completed physical measures, a 24-hr electrocardiogram, actigraphy sleep measurement, and questionnaires about trauma (Brief Trauma Questionnaire), childhood abuse (Child Trauma Questionnaire [CTQ]), mood, demographics, and medical/psychiatric history. Relations between trauma and HF-HRV were assessed in linear mixed effects models adjusting for covariates (age, race, education, body mass index, blood pressure, psychiatric history, medication use, sleep, mood, childhood abuse history). Results indicated that most women had experienced trauma. Any trauma exposure as well as a greater number of traumatic experiences were associated with lower HF-HRV during wake and particularly during sleep. Relations were not accounted for by covariates. Among midlife women, trauma exposure was related to lower HF-HRV during wake and sleep. Trauma may have an important impact on vagal influence over the heart, particularly during sleep. Decreased vagal influence over cardiac function may be a key mechanism by which trauma is associated with CVD risk.