Pub Date: Monday, Nov 30, 2020
Author: Licy L. Yanes Cardozo, MD and Damian G. Romero, PhD, FAHA
Affiliation: Departments of Cell & Molecular Biology and Medicine, University of Mississippi Medical Center
Cardiovascular disease (CVD) is the leading cause of death in women in developing and developed countries. 1 Although significant progress has been made in the field of CVD prevention, diagnosis and treatment, there is still ample room for improvement. In the clinic, physicians apply the same guidelines to both men and women, despite the overwhelming evidence from basic, translational, and clinical research showing sex differences in the pathophysiology of CVD. Although there is an increasing number of clinical trials that include women as participant subjects; a comprehensive gender-specific analysis of both the efficacy and the adverse effects of pharmacological and non-pharmacological interventions is still lacking. Health disparities are a pressing concern as CVD rates in the United States are significantly higher for African American or black females compared with their Caucasian or white counterparts. This race disparity is associated with a lower rate of awareness for heart disease and stroke among black women compared with white ones. 2 Sex differences in CVD diagnosis, treatment and management have been barely addressed in the clinical guidelines. The picture is even worse for the menopause transition period despite it being a physiological process that severely affect cardiovascular health and CVD outcomes in half of the human population. The sooner, the better will be that we recognize the menopause transition as a critical period in women’s life that should be specifically addressed to improve the wellbeing and health outcomes of this population.
The AHA Scientific Statement “The Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention” is a first step into filling the gap in our understanding of the overall picture of cardiovascular risk factors during the menopause transition. This scientific statement sheds light upon a period of time that is frequently ignored or underrecognized in women’s life. The menopausal transition is a period of time that starts when menstrual cycles become variable due to hormonal changes and other menopause-related symptoms begin, and ends with the final menstrual period. The menopausal transition is also a time where there is a marked increase in cardiovascular risks factors. It is during this period, when treating physicians have a golden opportunity to implement early effective interventions to mitigate the abrupt increase in cardiovascular risk factors in women.
Women’s reproductive aging is a complex physiological process that includes the menopausal transition and postmenopause stages, each of them also composed of multiple sub-stages. 3 Several meta-analyses have shown that women with “early onset” menopause (<45 years old) have a higher risk of overall or fatal coronary heart disease (CHD) or heart failure. 4,5 Those cardiac outcomes are probably due to an increase in cardiovascular risk factors during the late reproductive stage or the early menopausal transition as shown in multiple studies. In the Study of Women's Health Across the Nation (SWAN) 2,659 women aged 42-52 years at baseline were followed annually for up to 7 years (average, 3.9 years). 6 The SWAN study provided strong evidence that total cholesterol, low density lipoprotein cholesterol, triglycerides, and lipoprotein(a) peaked during late peri- and early postmenopause. 6 Similarly, a cross-sectional study of 2,037 Korean women aged 44-56 years clearly showed that systolic and diastolic blood pressure significantly increase between early and late menopausal transition. 7 Moreover, prevalence of hypertension was also significantly increased between early and late menopausal transition. 7 Those studies highlight that cardiovascular risk factors dramatically increase during the menopause transition pressing for a more in-depth approach to the menopause transition from the cardiological point of view in women’s health. We should move beyond the premenopausal-postmenopausal dichotomy in the clinical practice and embrace the overall menopause transition. Assessment of middle age premenopausal women reproductive health for early signs “early onset” menopause is critical. Those early signs are characterized by subtle changes in the flow and/or length of their menstrual cycle in the late reproductive or premenopausal stage. A detailed assessment of women’s reproductive health during clinical encounters will allow to identify those at risk of “early onset” menopause for whom a proactive approach will be highly beneficial. Evidence of the success of early interventions during the menopause transition in cardiovascular risk factors was clearly demonstrated in the Women’s Healthy Lifestyle Project (WHLP). In this randomized clinical trial, 535 healthy premenopausal women aged 44 to 50 years at baseline were randomized to an assessment-only control group or a 5-year cognitive-behavioral program that included a hypocaloric, reduced saturated fat and cholesterol diet, combined with moderately increased leisure-time physical activity. 8 The intervention prevented a rise in low density lipoprotein cholesterol observed in the control group during peri- to postmenopause. Moreover, the intervention prevented weight gain from pre- to peri- to postmenopause and reduced triglycerides, SBP and DBP, and blood glucose and insulin. 8 This is just an example of how detection of “early onset” menopause presents a unique opportunity to incorporate lifestyle modification, including dietary changes, exercise and weight loss, to prevent or delay development of cardiovascular risk factors. For basic science and translational researchers, this scientific statement is a call to elucidate the molecular mechanisms underlying the sharp increase in cardiovascular risk factors during the menopause transition, a period in women’s life with as much hormonal changes as in puberty. Moreover, the identification of the molecular mechanisms involved in these processes will allow the design of targeted therapies for a personalized medical approach.
Historically, women's health has been synonym to women’s reproductive health, and women’s health has been usually addressed by obstetrics and gynecology specialist physicians. As women currently spend 40% or more of their lives postmenopausal, a more effective approach is necessary to close the medical gap existing in women’s health management. This scientific statement is an exciting and necessary step forward in women’s health.
The writing group of the Prevention Science Committee of the Council on Epidemiology and Prevention (EPI) and Council on Cardiovascular and Stroke Nursing (CVSN) have done an outstanding job summarizing the current knowledge on the regulation and the effects of cardiovascular risk factors during the menopausal transition. Lack of knowledge is no longer an excuse to address women’s cardiovascular health concern during such period.
El Khoudary SR, Aggarwal B, Beckie TM, Hodis HN, Johnson AE, Langer RD, Limacher MC, Manson JE, Stefanick ML, Allison MA; on behalf of the American Heart Association Prevention Science Committee of the Council on Epidemiology and Prevention; and Council on Cardiovascular and Stroke Nursing. Menopause transition and cardiovascular disease risk: implications for timing of early prevention: a scientific statement from the American Heart Association [published online ahead of print November 30, 2020]. Circulation. doi: 10.1161/CIR.0000000000000912.
- Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, Newby LK, Piña IL, Roger VL, Shaw LJ, Zhao D, Beckie TM, Bushnell C, D'Armiento J, Kris-Etherton PM, Fang J, Ganiats TG, Gomes AS, Gracia CR, Haan CK, Jackson EA, Judelson DR, Kelepouris E, Lavie CJ, Moore A, Nussmeier NA, Ofili E, Oparil S, Ouyang P, Pinn VW, Sherif K, Smith SC, Jr., Sopko G, Chandra-Strobos N, Urbina EM, Vaccarino V, Wenger NK. Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the american heart association. Circulation. 2011;123:1243-1262.
- Ferris A, Robertson RM, Fabunmi R, Mosca L. American Heart Association and American Stroke Association national survey of stroke risk awareness among women. Circulation. 2005;111:1321-1326.
- Davis SR, Lambrinoudaki I, Lumsden M, Mishra GD, Pal L, Rees M, Santoro N, Simoncini T. Menopause. Nature reviews. Disease primers. 2015;1:15004.
- Muka T, Oliver-Williams C, Kunutsor S, Laven JS, Fauser BC, Chowdhury R, Kavousi M, Franco OH. Association of Age at Onset of Menopause and Time Since Onset of Menopause With Cardiovascular Outcomes, Intermediate Vascular Traits, and All-Cause Mortality: A Systematic Review and Meta-analysis. JAMA cardiology. 2016;1:767-776.
- Appiah D, Schreiner PJ, Demerath EW, Loehr LR, Chang PP, Folsom AR. Association of Age at Menopause With Incident Heart Failure: A Prospective Cohort Study and Meta-Analysis. Journal of the American Heart Association. 2016;5.
- Derby CA, Crawford SL, Pasternak RC, Sowers M, Sternfeld B, Matthews KA. Lipid changes during the menopause transition in relation to age and weight: the Study of Women's Health Across the Nation. Am. J. Epidemiol. 2009;169:1352-1361.
- Son MK, Lim NK, Lim JY, Cho J, Chang Y, Ryu S, Cho MC, Park HY. Difference in blood pressure between early and late menopausal transition was significant in healthy Korean women. BMC Womens Health. 2015;15:64.
- Kuller LH, Simkin-Silverman LR, Wing RR, Meilahn EN, Ives DG. Women's Healthy Lifestyle Project: A randomized clinical trial: results at 54 months. Circulation. 2001;103:32-37.
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-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association --