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Summary

Saad Samargandy et al [1] performed a post-hoc analysis including 339 women from the Heart Ancillary study of the SWAN (Study of Women’s Health Across the Nation) in order to assess changes in arterial stiffness in relation to the final menstrual period (FMP) and whether these changes differ between black and white mid-aged women. Subjects had ≤ 2 carotid-femoral pulse-wave velocity (cfPWV) exams over a period of 2.3 ± 0.5 years of follow-up. Annual percentage change in cfPWV varied by time segments: 0.9% (−0.6% to 2.3%) for >1 year before FMP, 7.5% (4.1% to 11.1%) within 1 year of FMP, and −1.0% (−2.8% to 0.8%) for >1 year after FMP, being the annual percentage change in cfPWV within 1 year of FMP significantly greater than the other time segments.

According to the authors, this difference is explained only in part by concurrent cardiovascular disease risk factors (from 5.9 to 7.5% in different models), but after adjusting for those factors, the time segment difference remains significant. As expected, black women had greater increase in cfPWV compared to white women. The authors concluded that the interval within 1 year of FMP is a critical period for women when vascular functional alterations occur, hence they recommend more intensive modifications in healthy lifestyles in women transitioning through the menopause.

Commentary

The present study aimed to characterize functional vascular changes in central arterial stiffness, in relation to FMP and to detect ethnical differences. The authors demonstrated significant increases in central arterial stiffness in the 1-year period surrounding the FMP in women transitioning through the menopause. This increase was independent of aging, midlife cardiovascular disease (CVD) risk factors, estradiol and FSH levels. Additionally, black women may experience greater adverse changes in arterial stiffness starting early in the transition than white women.
Previous cross-sectional surveys suggest that postmenopausal women have increased PWV measures compared with premenopausal ones. However, controlling for age is crucial as aging may confound these associations [2]. Therefore, to separate the different effects of chronological and reproductive aging into vascular stiffness, a survey of women through their menopausal transition is clearly required. It is to note, that using such design, previous results from the SWAN have shown that women who transitioned through the menopause had greater increase in central arterial stiffness compared with women who remained premenopausal or were postmenopausal at baseline [3]. In the present study, Samargandy et al [1] used a time-oriented analysis to describe when critical vascular changes occur in relation to the FMP. Interestingly, the increase in arterial stiffness within 1 year of the FMP remained significantly greater than the increase before 1 year before the FMP. Although the annual percentage increase in cfPWV within 1 year of FMP itself remained significantly different from zero after adjusting for midlife CVD risk factors, the data suggest that midlife CVD risk factors may explain part of the difference in arterial stiffness progression across the menopause transition.

Sexual steroids and gonadotropins oscillate during the menopause transition. Furthermore, estrogen receptors have been detected on vessel walls, and estradiol is thought to preserve arterial stiffness through vasodilation and vascular matrix formation [4]. However, in the present study, estradiol or FSH did not explain functional changes in central arteries observed during the menopausal transition. Other mechanisms, aside from classical CVD risk factors, may contribute to the changes observed in central arteries during the menopause transition. Systemic inflammation has been involved in the pathogenesis of arterial stiffness and the menopause transition is associated with a rise in chronic low-grade inflammation which may result in accelerating arterial stiffness. Additionally, an increase in waist circumference and visceral adiposity during the menopausal transition has been described, which leads to an increase in leptin and decrease in adiponectin levels that also may contribute to worsening arterial stiffness.
Finally, this survey emphasizes that menopausal transition is a critical stage in women’s life when changes in the vasculature and CVD risk factors may accumulate. These changes may increase the chance of CVD in the elder. In this sense, women should be advised that their cardiovascular health can be impaired during the menopausal transition and therefore, can be counseled to focus on lifestyle changes.

Camil Castelo-Branco
University of Barcelona, Barcelona, Spain

References

  1. Samargandy S, Matthews KA, Brooks MM, Barinas-Mitchell E, Magnani JW, Janssen I, Hollenberg SM, El Khoudary SR. Arterial Stiffness Accelerates Within 1 Year of the Final Menstrual Period: The SWAN Heart Study. Arterioscler Thromb Vasc Biol. 2020;40(4):1001-1008.
    https://pubmed.ncbi.nlm.nih.gov/31969013/
  2. O’Neill SM, Liu J, O’Rourke MF, Khoo SK. The menopausal transition does not appear to accelerate age-related increases in arterial stiffness. Climacteric. 2013;16:62–69.
    https://pubmed.ncbi.nlm.nih.gov/23152960/
  3. Khan ZA, Janssen I, Mazzarelli JK, et al. Serial Studies in subclinical atherosclerosis during menopausal transition (from the study of women’s health across the nation). Am J Cardiol. 2018;122:1161-1168.
    https://pubmed.ncbi.nlm.nih.gov/30077316/
  4. Blümel JE, Castelo-Branco C, Leal T, Gallardo L, Saini J, Ferron S, Haya J. Effects of transdermal estrogens on endothelial function in postmenopausal women with coronary disease. Climacteric. 2003;6(1):38-44.
    https://pubmed.ncbi.nlm.nih.gov/12725663/
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