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Summary

Zhu D et al. [1] pooled individual-level data from 23,365 women of six prospective studies which contributed to the InterLACE consortium. Women who experienced cardiovascular disease (CVD) events before baseline were excluded. The associations between frequency (never, rarely, sometimes and often), severity (never, mild, moderate and severe), and timing (before or after age at menopause  onset [i.e. early or late]) of VMS and incident CVD were analysed. In the adjusted model, women who reported night sweats “sometimes” (HR 1.22, 95% CI 1.02-1.45) or “often” (1.29, 1.05-1.58) had higher CVD risk. Increased severity of either hot flushes or night sweats was associated with higher CVD risk. The hazards ratios of CVD in women with severe hot flushes, night sweats and any VMS were 1.83 (1.22-2.73), 1.59 (1.07-2.37) and 2.11 (1.62-2.76), respectively. Women who reported severity for both hot flushes and night sweats had a higher CVD risk (1.55, 1.24-1.94) than those with hot flushes alone (1.33, 0.94- 1.88) and night sweats alone (1.32, 0.84-2.07). Women with either early onset (1.38, 1.10-1.75) or late onset (1.69, 1.32-2.16) VMS had an increased risk of incident CVD, compared with women who did not experience VMS.

Commentary

VMS have been associated with a less favorable cardiovascular risk profile and surrogate CVD endpoints [2]. Higher cholesterol, triglycerides, LDL-C, BMI, systolic blood pressure, diastolic blood pressure, insulin resistance [3], have been found in women with VMS. When compared to asymptomatic women, those with VMS had higher odds for hypertension and diabetes [4]. Similarly increased carotid intima media thickness has been found in women with moderate to severe hot flushes as compared to women with no or mild hot flushes [5]. Additionally reduced flow-mediated dilation (a marker of arterial endothelial dysfunction) and increased coronary artery calcium and aortic calcification were reported in women with hot flushes [6].  Although a prospective cohort study found that both hot flushes and night sweats were associated with higher coronary heart disease (CHD) risk [7],  a cross-sectional study found that the presence of night sweats rather than hot flushes were associated with increased CHD risk [8].  Hence, hot flushes and night sweats might have different aetiology with CVD [9].

The  disturbances in the autonomic nervous system and hypothalamic-pituitary-adrenal axis are believed to serve as the link between VMS and CVD. Previous studies used early and late onset VMS definitions either by using a fixed age, or by using VMS status at age of enrolment. Zhu et al [1], defined early or late onset VMS in relation to age at menopause. Self-reported VMS and sternal skin conductance measures of VMS did not always match, so were the night sweats.  Zhu et al. used self-reported hot flushes and night sweats and used time-varying VMS as the exposure rather than a single time-invariant variable, and adjusted for time-varying menopausal status and status of menopause hormone treatment (MHT). Studies showed the self-reported CVD had high validity and agreement with medical records.  Zhu et al. used self-reported CVD events as the outcome, they also assumed the bias caused by time-varying body mass index; and hypertension status was limited since the concordance in studies of InterLACE was reported to be around 80% before and after the menopause. The association between VMS and risk factors for CVD has conflicting evidence.  Some studies found no association between VMS and  lipid or fasting plasma glucose levels [2,9].  The study of Zhu et al. lacked information on lipid levels and diabetes status during women’s transition through the menopause. Even though these factors might confound or mediate the association between VMS and CVD events, the potential effect of lipid levels and diabetes status on the outcomes appears vague. The relationship between the extent of VMS and incident CVD event in that interval warrants the level of previous VMS to be taken into consideration. Nevertheless, this was not considered as an important predictor of current VMS.  The number  of cases with stroke was limited and this would warrant designing further studies with more participants. Despite this, the commented study of Zhu et al. [1] suggests that both  early-onset and late-onset VMS were associated with an increased risk of incident CVD and that the severity, rather than frequency, of both hot flushes and night sweats was associated with increased CVD risk.

Tevfik Yoldemir, MD, MA, PhD
Department of Obstetrics and Gynecology
Marmara Medical School, Istanbul, Turkey

References

  1. Zhu D, Chung HF, Dobson AJ, et al. Vasomotor menopausal symptoms and risk of cardiovascular disease: a pooled analysis of six prospective studies. Am J Obstet Gynecol. 2020;223(6):898.e1-898.e16.
    https://pubmed.ncbi.nlm.nih.gov/32585222/
  2. Kronenberg F, Cote LJ, Linkie DM, Dyrenfurth I, Downey JA. Menopausal hot flashes: thermoregulatory, cardiovascular, and circulating catecholamine and LH changes. Maturitas. 1984;6(1):31-43.
    https://pubmed.ncbi.nlm.nih.gov/6472126/
  3. Franco OH, Muka T, Colpani V, et al. Vasomotor symptoms in women and cardiovascular risk markers: Systematic review and meta-analysis. Maturitas. 2015;81(3):353-361.
    https://pubmed.ncbi.nlm.nih.gov/26022385/
  4. Herber-Gast GC, Mishra GD. Early severe vasomotor menopausal symptoms are associated with diabetes. Menopause. 2014;21(8):855-860.
    https://pubmed.ncbi.nlm.nih.gov/24398410/
  5. Thurston RC, El Khoudary SR, Tepper PG, et al. Trajectories of Vasomotor Symptoms and Carotid Intima Media Thickness in the Study of Women’s Health Across the Nation. Stroke. 2016;47(1):12-17.
    https://pubmed.ncbi.nlm.nih.gov/26578657/
  6. Thurston RC, Sutton-Tyrrell K, Everson-Rose SA, Hess R, Matthews KA. Hot flashes and subclinical cardiovascular disease: findings from the Study of Women’s Health Across the Nation Heart Study. Circulation. 2008;118(12):1234-1240.
    https://pubmed.ncbi.nlm.nih.gov/18765392/
  7. Herber-Gast G, Brown WJ, Mishra GD. Hot flushes and night sweats are associated with coronary heart disease risk in midlife: a longitudinal study. BJOG. 2015;122(11):1560-1567.
    https://pubmed.ncbi.nlm.nih.gov/25377022/
  8. Gast GC, Pop VJ, Samsioe GN, et al. Vasomotor menopausal symptoms are associated with increased risk of coronary heart disease. Menopause. 2011;18(2):146-151.
    https://pubmed.ncbi.nlm.nih.gov/21127438/
  9. Hitchcock CL, Elliott TG, Norman EG, Stajic V, Teede H, Prior JC. Hot flushes and night sweats differ in associations with cardiovascular markers in healthy early postmenopausal women. Menopause. 2012;19(11):1208-1214.
    https://pubmed.ncbi.nlm.nih.gov/22781788/

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