Menopause, hormone replacement therapy impact CV risk
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Cardiologists should consider a woman’s menopause status when assessing their CV risk, according to a presentation at the virtual American Society for Preventive Cardiology Congress on CVD Prevention.
“To lower a woman’s cardiovascular risk after menopause, it’s important to have a multifaceted approach to tackle all the ABCDEs that were outlined in the 2019 American College of Cardiology/American Heart Association primary prevention guidelines to help improve a woman’s risk through optimizing lifestyle and treating risk factors with pharmacotherapy as appropriate,” Cardiology Today Editorial Board Member Erin D. Michos, MD, MHS, FAHA, director of women’s cardiovascular health at Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, said during the presentation.
The average age of menopause is 51 years, with 1% going through menopause at 40 years of age and 5% experiencing it after 55 years of age. Factors that impact menopause age include tobacco use, maternal menopause age, BMI, alcohol use and socioeconomic status. Indications of menopause include disturbed sleep patterns, vasomotor symptoms and genitourinary symptoms, Michos said.
Several metabolic changes can occur at menopause such as an increase in adipose tissue deposition in the abdomen cavity, decrease in HDL and increases in LDL and triglycerides. In addition, menopause can lead to an insulin deregulation pattern of an increase in insulin resistance and a decrease in insulin secretion. Michos said, noting endothelial dysfunction may also occur and includes an increase in sympathetic tone and an increase in BP.
“Together, these can lead to accelerated cardiovascular risk after the menopause transition,” Michos said during the presentation.
Early menopause and CVD risk
Early menopause, particularly if it occurs in women younger than 50 years, is an independent risk factor for CVD, and some papers determined that premature menopause, defined as before age 40 years, increases the risk for CVD compared with menopause after age 50 years, she said.
“There’s a gradated risk with the younger age at time of menopause being associated with increased risk of CVD that’s attenuated but still significant even after you adjust for other covariates,” Michos said during the presentation.
These data led to the inclusion of premature menopause in the 2019 ACC/AHA Primary Prevention Guideline. This document emphasized that a history of premature menopause occurring before age 40 years and a history of pregnancy-associated conditions such as preeclampsia were risk-enhancing factors that increase the risk for atherosclerotic CVD.
Menopause leads to an abrupt decline in estrogen production. Research published in the Journal of the American College of Cardiology in 2018 by Michos and colleagues found that excess testosterone in women increased risk for CVD and HF even after adjustment for traditional risk factors.
She said several other papers determined that higher testosterone levels in women who were post-menopause were linked with increased risk for adverse cardiac remodeling, aortic stiffness, reduced brachial reactivity, atherosclerosis progression, increased N-terminal pro-B-type natriuretic peptide, CVD events and cognitive decline.
“It seems that increased androgens in women hallmark a woman at increased cardiovascular risk, but the question from our work is what do you do about that, because prior clinical trials of hormone therapy have not been shown to reduce cardiovascular risk, but we hope that our work provides some mechanistic understanding of the role that sex hormones play in a woman’s risk after menopause,” Michos said during the presentation.
Michos added that sex hormones after menopause may help to identify women at higher risk who may benefit from other risk-reduction strategies such as weight loss or statin therapy.
No guidelines currently recommend giving estrogen therapy for CV risk reduction, although it has been shown to have favorable effects on the CV system such as decreases in LDL, increases in HDL and dilation of blood vessels. There are some unfavorable effects of estrogen therapy, including increases in C-reactive protein, prothrombin and triglycerides and decreases in anti-thrombin III.
“There can be a procoagulant effect, and this may particularly [occur in] women at elevated CV risk. The unfavorable effects may outweigh the favorable benefits,” Michos said during the presentation.
Data from the Women’s Health Initiative published in JAMA in 2002 found that women who received combined hormone therapy with estrogen and progestin may have a twofold risk for venous thromboembolism. Women who received estrogen alone had elevated risk for stroke.
‘Risks are worrisome’
“Together, these risks are worrisome, and that’s why we don’t recommend hormone therapy for the purposes of cardiovascular disease prevention, but also don’t recommend its use in higher-risk women,” Michos said during the presentation.
These risks depend on the age of hormone therapy initiation, age at menopause, duration of therapy and time since menopause, in addition to the type, dose and route of hormone therapy, she said.
Vasomotor symptoms of menopause may be associated with increased CV risk. In data presented from the SWAN study, women who had frequent vasomotor symptoms had a 62% increased risk for a subsequent CV event over the next 20 years. Women with persistent vasomotor symptoms had a twofold increased risk for these events beyond 2 years.
“Again, they may hallmark a higher-risk woman, and we should pay attention,” Michos said during the presentation.
At the moment, hormone therapy is indicated for women younger than 60 years or within 10 years after menopause-onset with symptomatic vasomotor symptoms, and for women with early menopause without contraindications until at least the average age of natural menopause, according to the presentation.
Menopausal hormonal therapy is not recommended for women older than 65 years or those who are more than 10 years beyond menopause, nor is it recommended for primary or secondary prevention of CVD, Michos said, noting oral estrogens should be avoided in women with a history of venous thromboembolism CVD, gallbladder disease, hypertriglyceridemia or hypercoagulable state.
Menopause hormonal therapy should not be used for osteoporosis prevention and has not been shown to prevent cognitive decline, according to the presentation. The guideline principle for menopausal hormone therapy is to use a minimal dose for the shortest period of time required and to consider nonhormonal alternatives.
Regardless of the type of menopausal hormone therapy used, the ACC, AHA and the North American Menopause Society support shared decision making between clinicians and patients when deciding what therapy to take, Michos said.
Women with no known CVD should undergo a 10-year risk assessment with the Pooled Cohort Equation while taking into account risk enhances such as inflammatory disorders, family history and pregnancy-related disorders, and cardiologists may want to consider coronary artery calcium to guide shared decision making especially if their risk is uncertain, she said.
“Hormone therapy may be generally safe in women with a coronary artery calcium score of 0 if indicated,” Michos said during the presentation. “On the other hand, I tend to recommend avoiding hormone therapy, particularly systemic hormone therapy, in women with significantly elevated calcium scores of 100 or 300 because they have higher event rates and I consider them more like a secondary prevention population. A CAC score is a very good prognostic marker of risk because it integrates a lifetime of risk exposure of both traditional risk factors and novel and unmeasured risk factors because you’re measuring the atherosclerosis burden itself.”
References:
- Thurston RC et al. Session S 1. Presented at: North American Menopause Society 2019 Annual Meeting; September 25-28, 2019; Chicago.
- Writing Group for the Women’s Health Initiative Investigators. JAMA. 2002;doi:10.1001/jama.288.3.321.
- Zhao D, et al. J Am Coll Cardiol. 2018;doi:10.1016/j.jacc.2018.01.083.
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Michos ED. Menopause and Its Impact on Women’s Cardiovascular Health. Presented at: American Society for Preventive Cardiology Congress on CVD Prevention; July 25-26, 2020 (virtual).
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