Abstract and Introduction
Abstract
Objective: The aim of the study was to compare the endothelial function of symptomatic (self-reported hot flashes >3 on a scale of 0–10) versus asymptomatic (≤3) women in different postmenopause stages, and to examine if the association between hot flashes and endothelial function was independent of classical cardiovascular risk factors observed during the analysis.
Methods: Noninvasive venous occlusion plethysmography within two groups: recent (recent postmenopause [RPM], <10 y, n = 63) and late (late postmenopause [LPM], ≥10 y, n = 67) postmenopause.
Results: Symptomatic women showed lower forearm blood flow and lower percentage increment of it during the reactive hyperemia response; higher systolic (P < 0.0001 in RPM and P = 0.0008 in LPM) and diastolic (P = 0.0005 in RPM and P = 0.0219 in LPM) blood pressure; highest score for perimenopausal hot flashes (P = 0.0007 in RPM and P < 0.0001 in LPM), longer duration of prior oral contraceptive use (P = 0.009 in RPM and P = 0.0253 in LPM), and higher current sleep disorders (P < 0.0001 in RPM and P = 0.0281 in LPM) compared with asymptomatic ones. In the LPM group, symptomatic women also had higher prevalence of previous hypertension diagnosis (P = 0.0092). During multivariate analysis, blood flow during the reactive hyperemia response was associated with hot flashes after adjusting for age, body mass index, and systolic blood pressure (odds ratio 0.55 [0.36–0.84] in RPM and odds ratio 0.7 [0.5–0.97] in LPM).
Conclusions: In both phases, recent and late post menopause, hot flashes were associated with endothelial dysfunction and higher systolic and diastolic blood pressure, but the relationship between hot flashes and endothelial dysfunction was independent of blood pressure.
Introduction
The prevalence of hot flashes during menopause has been described as up to 80% in most societies, being influenced by different factors such as age, ethnicity, education, smoking, and anxiety.[1] Hot flashes were reported to last on an average 7.4 years, but for reasons not entirely clear some women remained symptomatic for more than 11.8 years.[2] Apart from worsening of quality of life,[3] new studies have reported that women with hot flashes have an increased risk of subclinical cardiovascular (CV) disease,[4] as well as of CV events.[5] Different associations, however, have been described according to age and time since menopause. In a reanalysis of the Women's Health Initiative (WHI),[6] in the subgroup of 70 to 79-year-old women with moderate/severe hot flashes, CV events after hormone therapy (HT) were five times more likely to occur compared with the ones of the same age who used placebo. In 50 to 69-year-old women, no increased risk of CV events after HT, however, could be observed related to presence of hot flashes.
The Swan Heart Study, analyzing women during the menopausal transition—42 to 58 years old—described that those with hot flashes presented lower flow-mediated dilatation (FMD) of the brachial artery, evaluated by Doppler, and larger aortic and coronary calcifications, visualized by electron beam tomography, compared with the ones without hot flashes, even adjusting for age, body mass index (BMI), menopausal status, systolic and diastolic blood pressures (SBP and DBP), smoking, levels of cholesterol, triglycerides, glucose, and estradiol.[7] Another article from the same cohort reported increased carotid artery intima thickness (0.02 ± 0.01 mm) in symptomatic versus asymptomatic women.[4] Such discrepancies made us to question at what time during postmenopause and how intense hot flashes must be to be valued as emerging CV risk markers, or if they just come together with classical CV risk factors such as obesity, hypertension, and diabetes.
To encompass CV risk assessment in younger women in recent (<10 y) postmenopause, endothelial function seems to be the most appropriate parameter because its dysfunction is considered the earliest sign of atherosclerotic disease,[8] already demonstrated in different CV risk factors, such as hypercholesterolemia, hypertension, smoking, and diabetes,[9] and also in menopause,[10] before any structural vessel change.[11] Endothelial dysfunction results from an imbalance in the production of vasodilator, particularly nitric oxide (NO), and vasoconstrictor substances, causing increased vascular tone, cellular adhesion, and platelet aggregation.[9] Techniques validated for endothelial function assessment include brachial artery ultrasound, video capillaroscopy, and noninvasive venous occlusion plethysmography (VOP).[12] The latter measures forearm blood flow through the variation of its circumference at baseline and after the reactive hyperemia response, induced by ischemia and subsequent release of the segment. The reperfusion maneuver mimics what physiologically happens in daily life by increased physical activity, when shear stress up-regulates endothelial NO production. A lower reactive hyperemia response reflects reduced NO bioavailability to the swirling of blood endogenous stimuli.[13]
The objectives of our study were to compare, in both late and recent postmenopause, symptomatic versus asymptomatic women's endothelial function; and to examine if the association between endothelial function and hot flashes was independent, considering other observed factors that could affect CV risk.
Menopause. 2016;23(8):846-855. © 2016 The North American Menopause Society
