‘Evidence of synergy’: Short sleep, hot flashes associated with CV risk in menopause
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Frequent hot flashes are associated with indicators of cardiovascular disease among midlife and older women; poor sleep and trauma history may act synergistically with vasomotor symptoms to further increase risk, according to a speaker.
“Factors associated with cardiovascular disease risk in women go beyond our standard risk factors, such as blood pressure and obesity,” Rebecca Thurston, PhD, president of the North American Menopause Society, professor of psychiatry, psychology and epidemiology and director of the women’s biobehavioral health program at the University of Pittsburgh, told Healio. “When we consider women’s cardiovascular health, we need to move beyond an exclusive focus on our standard CVD risk factors and consider both psychosocial and menopause-related risk factors.”
CVD among women has “unique features,” including a role for the menopause transition, Thurston said during an online presentation at the virtual North American Menopause Society annual meeting. Menopause occurs directly before the onset of clinical CVD among women, and CV events, such as myocardial infarction, occur later in the life span for women vs. men.
“These events are relatively rare premenopause, but these events accelerate starting with peri- and postmenopause to ultimately match that of men,” Thurston said. “The menopause can be seen as a time of accelerated CVD risk.”
Signs of subclinical disease
Analyses from the Study of Women’s Health Across the Nation, a large, longitudinal cohort of women transitioning through menopause conducted over 20 years, show a subset of women who underwent ultrasound of the carotid arteries had accelerated accumulation of intima-media thickness — a sign of subclinical atherosclerosis — during the late perimenopausal period compared with early menopause, with results persisting after adjustment for age. Findings were similar for vascular stiffness, incident metabolic syndrome and adverse changes in lipid profile around the final menstrual period. The data support that menopause itself is associated with accelerated vascular risk beyond aging alone, Thurston said.
Decreases in estradiol, increases in follicle-stimulating hormone observed around the time of the final menstrual period “are not the whole story,” Thurston said. Research from the Women’s Health Initiative and the Heart and Estrogen-Progestin Replacement Study show that vasomotor symptoms, which can last from 7 to 10 years for some women, are a modifier of the relationship between hormone therapy use and CV events, as measured by flow-mediated dilation, endothelial dysfunction and intima-media thickness.
Role of sleep
More than 50% of midlife women report trouble with sleep during the menopause transition, with sleep problems increasing during menopause, Thurston said.
“We know that poor, particularly short sleep has been associated with CVD risk, including a 50% increase in coronary heart disease mortality,” Thurston said. “It all begs the question: What is going on during the menopause transition? This is a time of poor sleep and vascular vulnerability.”
In the MS HEART cohort, women with shorter sleep time, defined as 5 or fewer hours, had significantly elevated odds for developing carotid artery plaque vs. women who slept longer, Thurston said. Associations persisted after multiple adjustments for other CV risk factors, mood, sleep apnea and hormone use. Short sleepers also had a proinflammatory profile compared with longer sleepers.
The research also showed that vasomotor symptoms were associated with acute awakenings, but the hot flashes did not explain the associations between sleep time and vascular measures.
“However, there was evidence of a synergy, such that women with short sleep and above the median number of hot flashes overnight had the highest [intima-media thickness],” Thurston said.
Psychosocial factors
Depression, anxiety and low socioeconomic status all have implications for vascular health, Thurston said. New research shows that a history of violence and trauma are also associated with CV risk.
“We were struck that 60% of these MS HEART women endorsed at least one of these traumatic experiences in their lifetime; the most prevalent being sexual assault ... followed by workplace sexual harassment, endorsed by 20% of women,” Thurston said. “We found that the more traumatic experiences you had in your lifetime, the lower your [flow-mediated dilation], meaning the poorer your endothelial function, relative to those women who reported none.”
Women with a history of sexual assault had quadruple the odds for developing elevated carotid plaque in MS HEART, with the associations persisting at follow-up 5 years later, she said.
“These women with a history of sexual assault had greater plaque progression over the course of midlife than the women without sexual assault,” Thurston said.
‘There is more to do’
More work in these areas are needed, Thurston said. New research with 20 women from MS HEART who underwent brain imaging showed greater amounts of white matter in the brain — a sign of small vessel disease in the brain — among women with more physiologically monitored hot flashes during sleep.
“Based upon these data, we have set up the MS BRAIN study, inviting 230 women from MS HEART back to undergo brain imaging and cognitive testing,” she said. Preliminary data from MS BRAIN show that women who wake more during the night had greater white matter hyperintensities in the brain.
“We need to understand the mechanisms by which these factors are linked to CV health,” Thurston told Healio. “We have identified some of these mechanisms, but there is more to do. We further need to understand whether intervening on them at midlife can reduce women’s later CVD risk.”
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Thurston RC. Women’s cardiovascular health at midlife: The role of hot flashes, sleep problems and trauma. Presented at: North American Menopause Society annual meeting; Sept. 28-Oct. 3, 2020 (virtual meeting).
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