FROM ACC 15

For women in midlife, an earlier age of onset of vasomotor symptoms – hot flashes and night sweats – was linked to impaired endothelial function, a very early marker for cardiovascular disease.

In the first of two related studies, an earlier age of onset for vasomotor symptoms (VMS) was associated with increased endothelial dysfunction as measured by brachial artery ultrasound. Greater frequency of hot flashes was associated with endothelial dysfunction for younger but not older participants in the second study.

Though more than 70% of women experience VMS during perimenopause and menopause, these symptoms largely have been viewed as a quality of life issue. However, this emerging research might mean that early onset of of hot flashes might serve a potential marker for increased risk for cardiovascular disease, said Rebecca C. Thurston, Ph.D., associate professor of psychiatry, psychology, and epidemiology at the University of Pittsburgh. Her work was presented in a briefing in advance of the annual meeting of the American College of Cardiology in San Diego.

Dr. Thurston and her colleagues drew from the Women’s Ischemia Syndrome Evaluation ( WISE ) study to evaluate 104 women at four study sites. Participants were postmenopausal and at least 50 years old, could not be on hormone replacement therapy, and had their ovaries. Women with any signs or symptoms of ischemia were excluded, and multiple potential confounders were assessed in the study’s extensive evaluation. Women were stratified by onset of VMS by self-report into three groups: those who never had VMS, those whose VMS began at age 42 or earlier, and those whose VMS began after the age of 42.

Women in the WISE study underwent brachial artery ultrasound to assess brachial artery flow mediated dilation (FMD), a known preclinical disease marker that has been linked to clinical outcomes. Lower FMD scores indicate poorer endothelial function. Women in the group with the earliest onset of VMS had significantly lower FMD values (P = 0.038), indicating poorer endothelial dysfunction. The effect persisted even after controlling for potentially confounding factors.

The second trial, the MSHeart Study , enrolled 189 women aged 40-60. All were nonsmokers with no history of CVD. All of the women had intact uteri and ovaries, and enrollees could not be using hormones or other medications that could affect vascular function (beta-blockers, calcium channel blockers, insulin, or selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors). Participants again underwent extensive evaluation.

Women in the MSHeart Study received a full 24 hours of objective physiologic hot flash monitoring via an external monitoring system as well as FMD evaluation by brachial artery ultrasound. Women were stratified by age into three groups: younger than 53, 53-56, and greater than age 56.

For the youngest group of women in the second study, increased frequency of objectively verified hot flashes was associated with lower FMD and poorer endothelial dysfunction (P < 0.05). The association was not significant for either of the older two groups when taken separately; however, when pooled data for participants of all ages were considered, the interaction between age and hot flash frequency was associated with reduced FMD (P = 0.02). These associations held true after adjusting for the covariates of age, race, BMI, blood vessel diameter, menopausal stage, and any prior hormone use.

These two studies, said Dr. Thurston, “may point to subgroups of women that need targeted cardiovascular prevention” by identifying early VMS as a mechanistic pathway for endothelial dysfunction. Dr. Richard Chazal, ACC vice president and session moderator, noted that the MSHeart Study in particular succeeded in “leveraging physiologic symptoms and markers, as well as the flow mediated functional dilation that we all would expect.”

The studies were sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Health.

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