Rebecca C. Thurston

Hot Flashes and Subclinical Cardiovascular Disease Findings From the Study of Women’s Health Across the Nation Heart Study

Background— Although evidence suggests adverse vascular changes among women with hot flashes, it is unknown whether hot flashes are associated with subclinical cardiovascular disease. The aim of this study was to examine relations between menopausal hot flashes and indices of subclinical cardiovascular disease. We hypothesized that women with hot flashes would show reduced flow-mediated dilation and greater coronary artery and aortic calcification compared with women without hot flashes. Methods and Results— The Study of Women’s Health Across the Nation Heart Study (2001 to 2003) is an ancillary study to the Study of Women’s Health Across the Nation, a community-based cohort study. Participants were 492 women (35% black, 65% white) 45 to 58 years of age who were free of clinical cardiovascular disease and had a uterus and at least 1 ovary. Measures included a brachial artery ultrasound to assess flow-mediated dilation, electron beam tomography to assess coronary artery and aortic calcification, reported hot flashes (any/none, previous 2 weeks), and a blood sample for measurement of estradiol concentrations. Cross-sectional associations were evaluated with linear regression and partial proportional odds models. Hot flashes were associated with significantly lower flow-mediated dilation (&bgr;=−1.01; SE, 0.41; P=0.01) and greater coronary artery (odds ratio, 1.48; 95% confidence interval, 1.04 to 2.12) and aortic (odds ratio, 1.55; 95% confidence interval, 1.10 to 2.19) calcification in age- and race-adjusted models. Significant associations between hot flashes and flow-mediated dilation (&bgr;=−0.97; SE, 0.44; P=0.03) and aortic calcification (odds ratio, 1.63; 95% confidence interval, 1.07 to 2.49) remained in models adjusted for cardiovascular disease risk factors and estradiol. Conclusions— Women with hot flashes had reduced flow-mediated dilation and greater aortic calcification. Hot flashes may mark adverse underlying vascular changes among midlife women.

Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition

IMPORTANCE The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments. OBJECTIVES To determine total duration of frequent VMS (≥ 6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence. DESIGN, SETTING, AND PARTICIPANTS The Study of Womens Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS. MAIN OUTCOMES AND MEASURES Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause. RESULTS The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, >11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS. CONCLUSIONS AND RELEVANCE Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women.

Women, loneliness, and incident coronary heart disease.

Objective: To examine associations between loneliness and risk of incident coronary heart disease (CHD) over a 19-year follow-up period in a community sample of men and women. Loneliness, the perceived discrepancy between actual and desired social relationships, has been linked to several adverse health outcomes. However, no previous research has prospectively examined the association between loneliness and incident CHD in a community sample of men and women. Methods: Hypotheses were examined using data from the First National Health and Nutrition Survey and its follow-up studies (n = 3003). Loneliness, assessed by one item from the Center for Epidemiologic Studies of Depression scale, and covariates were derived from baseline interviews. Incident CHD was derived from hospital records/death certificates over 19 years of follow-up. Hypotheses were evaluated, using Cox proportional hazards models. Results: Among women, high loneliness was associated with increased risk of incident CHD (high: hazard ratio = 1.76, 95% Confidence Interval = 1.17–2.63; medium: hazard ratio = 0.98, 95% Confidence Interval = 0.64–1.49; reference: low), controlling for age, race, education, income, marital status, hypertension, diabetes, cholesterol, physical activity, smoking, alcohol use, systolic and diastolic blood pressures, and body mass index. Findings persisted additionally controlling for depressive symptoms. No significant associations were observed among men. Conclusions: Loneliness was prospectively associated with increased risk of incident CHD, controlling for multiple confounding factors. Loneliness among women may merit clinical attention, not only due to its impact on quality of life but also its potential implications for cardiovascular health. CHD = coronary heart disease; SBP = systolic blood pressure; NHANES I = First National Health and Nutrition Examination Survey; CESD = Center for Epidemiologic Studies of Depression; BMI = body mass index; ICD-9 = International Classification of Diseases, Ninth Revision.

Factors Related to Age at Natural Menopause: Longitudinal Analyses From SWAN

Early age at the natural final menstrual period (FMP) or menopause has been associated with numerous health outcomes and might be a marker of future ill health. However, potentially modifiable factors affecting age at menopause have not been examined longitudinally in large, diverse populations. The Study of Womens Health Across the Nation (SWAN) followed 3,302 initially premenopausal and early perimenopausal women from 7 US sites and 5 racial/ethnic groups, using annual data (1996-2007) and Cox proportional hazards models to assess the relation of time-invariant and time-varying sociodemographic, lifestyle, and health factors to age at natural FMP. Median age at the FMP was 52.54 years (n = 1,483 observed natural FMPs). Controlling for sociodemographic, lifestyle, and health factors, we found that racial/ethnic groups did not differ in age at the FMP. Higher educational level, prior oral contraceptive use, and higher weight at baseline, as well as being employed, not smoking, consuming alcohol, having less physical activity, and having better self-rated health over follow-up, were significantly associated with later age at the FMP. These results suggest that age at the natural FMP reflects a complex interrelation of health and socioeconomic factors, which could partially explain the relation of late age at FMP to reduced morbidity and mortality.

Emotional antecedents of hot flashes during daily life.

Objective: Hot flashes are among the most frequently reported menopausal symptoms. However, little is known about factors associated with their occurrence. Moreover, despite the wide use of self-report hot flash measures, little is known about their concordance with physiological flashes. This study evaluated emotional and behavioral antecedents of subjectively and objectively measured hot flashes during daily life. It also examined individual differences predicting concordance between objective and subjective hot flashes. Methods: Forty-two perimenopausal or postmenopausal women (mean age = 50.5 ± 4.8 years) reporting daily hot flashes completed 2 days of ambulatory sternal skin conductance monitoring, behavioral diaries 3 times an hour, and psychometric questionnaires. Hot flashes meeting objective physiological criteria and subjectively reported flashes not meeting physiological criteria were assessed. Likelihood of hot flashes following emotions and activities were examined in a case-crossover analysis. Results: Relative to nonflash control times, objective hot flashes were more likely after increased happiness, relaxation, and feelings of control, and less likely after increased frustration, sadness, and stress. Conversely, subjective hot flashes not meeting physiological criteria were more likely after increased frustration and decreased feelings of control. Questionnaires revealed increased negative mood and negative attitudes were associated with fewer objective flashes and higher false-positive reporting rates. Conclusion: Increased positive and decreased negative emotions were associated with objective hot flashes, whereas increased negative and decreased positive emotions were associated with subjective flashes not meeting physiological criteria. The anecdotal association between negative emotions and hot flashes may be the result of self-reported flashes lacking physiological corroboration. HRT = hormone replacement therapy; BDI-II = Beck Depression Inventory, Second Revision; STAI = State Trait Anxiety Inventory; DSI = Daily Stress Inventory; SCL-90-R = Symptom Checklist-90, Revised; RR = rate ratio.

Vasomotor symptoms and menopause: findings from the Study of Women's Health across the Nation.

Vasomotor symptoms (VMS), or hot flashes and night sweats, are often considered the cardinal symptoms of menopause. SWAN, one of the largest and most ethnically diverse longitudinal studies of the menopausal transition, has allowed unique insights into VMS. Specifically, SWAN has helped yield important information about the prevalence of, racial/ethnic differences in, risk factors for, and implications of VMS for midlife womens mental and physical health. We have reviewed the literature on VMS, emphasizing findings that have emerged from SWAN and new areas of inquiry in the area of VMS.

Beyond frequency: who is most bothered by vasomotor symptoms?

Objective: Most menopausal women report vasomotor symptoms (hot flashes, night sweats). However, not all women with vasomotor symptoms, including frequent symptoms, are bothered by them. The primary aim was to identify correlates of vasomotor symptom bother beyond symptom frequency. Design: The Study of Womens Health Across the Nation participants reporting vasomotor symptoms at annual visit 7 comprised the sample (N = 1,042). Assessments included hot flash and night sweats frequency (number per week) and bother (1, not at all- 4, very much). Negative affect (index of depressive symptoms, anxiety, perceived stress, negative mood), symptom sensitivity, sleep problems, and vasomotor symptom duration (number of years) were examined cross-sectionally in relation to bother in ordinal logistic regression models with symptom frequency and covariates. Hot flashes and night sweats were considered separately. Results: In multivariable models controlling for hot flash frequency, negative affect (odds ratio [OR] = 1.27, 95% CI: 1.08-1.51), symptom sensitivity (OR = 1.18, 95% CI: 1.03-1.37), sleep problems (OR = 1.38, 95% CI: 1.04-1.85), poorer health (OR = 1.24, 95% CI: 1.03-1.48), duration of hot flashes (OR = 1.14, 95% CI: 1.06-1.23), younger age (OR = 0.94, 95% CI: 0.89-0.99), and African American race (vs white, OR = 1.59, 95% CI: 1.12-2.26) were associated with hot flash bother. After controlling for night sweats frequency and covariates, sleep problems (OR = 1.84, 95% CI:1.33-2.55) and night sweats duration (OR = 1.10, 95% CI: 1.02-1.20) were associated with night sweats bother. Conclusions: Beyond frequency, factors associated with bothersome hot flashes include mood, symptom sensitivity, symptom duration, sleep problems, age, and race. Correlates of bothersome night sweats include sleep problems and symptom duration. In addition to reducing frequency, interventions for vasomotor symptoms might consider addressing modifiable factors related to symptom bother.

Gains in Body Fat and Vasomotor Symptom Reporting Over the Menopausal Transition The Study of Women's Health Across the Nation

Although most women report vasomotor symptoms (hot flashes, night sweats) during midlife, their etiology and risk factors are incompletely understood. Body fat is positively associated with vasomotor symptoms cross-sectionally, but the longitudinal relation between changes in body fat and vasomotor symptoms is uncharacterized. The study aim was to examine whether gains in body fat were related to vasomotor symptom reporting over time. Measures of bioelectrical impedance for body fat, reproductive hormones, and reported vasomotor symptoms were assessed annually over 4 years from 2002 to 2006 among 1,659 women aged 47-59 years participating in the Study of Womens Health Across the Nation. Body fat change was examined in relation to vasomotor symptoms by using generalized estimating equations. Body fat gains were associated with greater odds of reporting hot flashes in models adjusted for age, site, race/ethnicity, education, smoking, parity, anxiety, and menopausal status (relative to stable body fat, gain: odds ratio = 1.23, 95% confidence interval: 1.02, 1.48; P = 0.03; loss: odds ratio = 1.07, 95% confidence interval: 0.89, 1.29; P = 0.45). Findings persisted controlling for estradiol, the free estradiol index, or follicle-stimulating hormone concentrations. The relations between body fat changes and night sweats were not statistically significant. Body fat gains are associated with greater hot flash reporting during the menopausal transition.

Hot flashes and carotid intima media thickness among midlife women.

Objective: Emerging evidence suggests associations between menopausal hot flashes and cardiovascular risk. However, whether hot flashes are associated with intima media thickness (IMT) or IMT changes over time is unknown. We hypothesized that reported hot flashes would be associated with greater IMT cross-sectionally and with greater IMT progression over 2 years. Methods: Participants were 432 women aged 45 to 58 years at baseline participating in the Study of Womens Health Across the Nation (SWAN) Heart, an ancillary study to the SWAN. Measures at the SWAN Heart baseline and follow-up visit 2 years later included a carotid artery ultrasound, reported hot flashes (past 2 weeks: none, 1-5 d, ≥6 d), and a blood sample for measurement of estradiol. Results: Women reporting hot flashes for 6 days or more in the prior 2 weeks had significantly higher IMT than did women without hot flashes at the baseline (mean [SE] difference, 0.02 [0.01] mm; P = 0.03) and follow-up (mean [SE] difference, 0.02 [0.01] mm; P = 0.04) visits, controlling for demographic factors and cardiovascular risk factors. Reporting hot flashes at both study visits was associated with higher follow-up IMT relative to reporting hot flashes at neither visit (mean [SE] difference, 0.03 [0.01] mm; P = 0.03). Associations between hot flashes and IMT largely remained after adjusting for estradiol. An interaction between hot flashes and obesity status was observed (P = 0.05) such that relations between hot flashes and IMT were observed principally among overweight/obese women. Hot flashes were not associated with IMT progression. Conclusions: These findings provide some indication that women reporting hot flashes for 6 days or more in the prior 2 weeks may have higher IMT than do women without hot flashes, particularly for women who are overweight or obese. Further work should determine whether hot flashes mark adverse underlying vascular changes.

Burden of Subclinical Cardiovascular Disease in “Metabolically Benign” and “At-Risk” Overweight and Obese Women: The Study of Women's Health Across the Nation (SWAN)

BACKGROUND Metabolically benign obese individuals have a 10-year cardiovascular disease (CVD) risk comparable to healthy normal weight individuals. However, the burden of subclinical CVD among metabolically benign obese is not well known. METHODS In cross-sectional analyses of 475 mid-life women, we compared common carotid artery intima media thickness (CCA-IMT), aortic pulse wave velocity (aPWV) and coronary (CAC) and aortic calcification (AC) among three groups: healthy normal weight, metabolically benign overweight/obese (<3 metabolic syndrome components/elevated CRP), and at-risk overweight/obese (≥3 metabolic syndrome components/elevated CRP). RESULTS The mean (SD) CCA-IMT and aPWV were lowest in the normal weight group (n=145), followed by the benign overweight/obese (n=260) and at-risk overweight/obese (n=70) groups [CCA-IMT: 0.64 (0.08) vs. 0.68 (0.09) vs. 0.73 (0.13) mm, p<0.001; aPWV: 731.0 (176.4) vs. 809.9 (182.3) vs. 875.7 (228.8) cm/s, p<0.001]. Similar results were found for the frequency (%) of women with increased CAC and AC [CAC: 13 (9%) vs. 53(20%) vs. 28(40%), p<0.001; AC: 47(32%) vs. 130 (50%) vs. 55(79%), p<0.001]. These differences remained significant after multivariable adjustment. Further adjustment for BMI attenuated the statistical significance of differences in aPWV and calcification between benign and at-risk overweight/obese women, but had little effect on the magnitude of these differences. CONCLUSIONS Metabolically benign overweight/obese women have a significantly greater subclinical CVD burden than normal weight women, despite published data finding similar CVD event rates between the two groups. Prospective studies tracking the progression of subclinical atherosclerosis to clinical CVD in these women are needed.