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Changes in Heart Rate Variability during Vasomotor Symptoms among Midlife Women

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.

Child Abuse and Neglect and Subclinical Cardiovascular Disease among Midlife Women

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.

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
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.