Gregory Weiss, MD: Managing Cardiovascular Disease Risk During Menopause

Gregory Weiss, MD

Cardiovascular disease (CVD) remains the leading cause of death in the world. This fact holds true for women as well as men.¹ In the last two decades observational studies have noticed that the risk for coronary heart disease increases significantly following the transition into menopause.² While women generally develop coronary heart disease (CHD) later than men, a clear inflection point at midlife warranted an explanation. Studies looking for a reason for this increase in CHD risk discovered distinct patterns of alterations in endogenous sex hormones that resulted in adverse changes in body fat, lipids, and lipoproteins, as well as structural and functional measures of overall vascular health.³ These revelations have led the American Heart Association (AHA) to release a scientific statement addressing the implications of menopausal transitioning on CVD in women.

The last AHA guidelines addressing CVD prevention in women were released in 2011. In the time since then much more has been discovered about the complexities of the menopausal transition (MT) with major implications on CV risk for women in midlife. The primary hormonal changes experienced through the five stages of the MT involve estradiol and follicle-stimulating hormone levels. Typically, estradiol levels begin to fall before the final menstrual period while levels of follicle-stimulating hormone rise.² While these changes may lead to the symptoms women experience during the MT, researchers have found that the symptoms themselves may herald ominous CV changes.

Symptoms women commonly experience during the MT include hot flashes and night sweats, mood changes, sleep and cognitive disturbances, genitourinary, and sleep function changes. Hot flashes and night sweats are examples of vasomotor symptoms that may occur in conjunction with higher body fat composition and are associated with cigarette smoking, depression and lower educational level.² Vasomotor disturbances may also be responsible for some measure of increased CV risk.

Five characteristics of menopause have been found to influence CV risk. Studies have shown that women who experience menopause at less than 45 years of age experience exhibit significantly higher cardiovascular risk when compared to those who are older. Data from the Framingham Heart Study showed that earlier menopause was associated with increased CVD but also that high cholesterol, systolic blood pressure, and diastolic blood pressure led to earlier menopause.² This points to a clear association between preexisting CV risk factors and the MT leading to decreased CV health.⁴

The second characteristic is type of menopause. Some studies showed that the risk for CHD was higher if menopause was caused by surgical removal of the ovaries when no estrogen therapy was prescribed.5 This theory was modified when it was found that the timing of surgical menopause was important. Surgical removal of the ovaries at a young age increased the risk of CHD while removal at the time of normal menopause did not.²

The third characteristic is the stage of menopause where it appears that the most deleterious changes in blood pressure and intima-medial arterial thickening occur during the later stages of menopause.² Endogenous estradiol levels have also been shown to affect CV risk with higher levels being associated with lower progression of carotid narrowing over time.²

Finally, the previously mentioned vasomotor symptoms of menopause correlate to reduced flow-mediated dilation and greater aortic calcification independent of other CVD risk factors or hormonal levels.⁶

In addition to lifestyle behavior modification in the form of weight loss and smoking cessation, the evidence suggests a role for menopausal hormone therapy (MHT).² It appears that initiating MHT before the age of 60 or within less than 10 years since menopause confers a CV risk-benefit while later initiation may increase risk.² Treatment with MHT may also mitigate other comorbidities by promoting lean body mass and lower body mass index as well as decreased levels of fasting glucose. Once started stopping MHT increased the risk of CVD in menopausal women.² Finally, while data for primary and secondary prevention of atherosclerotic disease and improved survival with lipid-lowering interventions is lacking, there may be a role for such therapy during the MT.²

It is clear that the MT is a uniquely impactful facet of a woman’s cumulative cardiovascular risk deserving of close attention. Clinicians need to recognize the changes that occur and armed with the knowledge in the scientific statement, educate patients, tailor interventions, and provide the treatment women need to navigate this unique time. Through encouragement of lifestyle changes, management of other risk factors for CVD, and patient-specific approaches to MHT women can realize increased quality of life, reduced CV risk, and potentially a longer and more satisfying life.

References:

1. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, et al; on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart dis- ease and stroke statistics—2019 update: a report from the American Heart Association [published correction appears in Circulation. 2020;141:e33]. Circulation. 2019;139:e56–e528. doi: 10.1161/CIR.0000000000000659
2. Samar R. El Khoudary, Brooke Aggarwal, Teresa M. Beckie, et al. Menopause transition and cardiovascular disease risk: implications for timing of early prevention. A scientific statement from the American heart association. Circulation. 2020;142:00–00. DOI: 10.1161/CIR.0000000000000912
3. El Khoudary SR. Gaps, limitations and new insights on endogenous estro- gen and follicle stimulating hormone as related to risk of cardiovascular disease in women traversing the menopause: a narrative review. Maturitas. 2017;104:44–53. doi: 10.1016/j.maturitas.2017.08.003
4. Muka T, Oliver-Williams C, Kunutsor S, Laven JS, et al. 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 Cardiol. 2016;1:767–776. doi: 10.1001/jamacardio.2016.2415
5. Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and the risk of coronary heart disease in women. N Engl J Med. 1987;316:1105–1110. doi: 10.1056/NEJM198704303161801
6. Hurston 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;118:1234–1240. doi: 10.1161/CIRCULATIONAHA.108.776823