The American Heart Association (AHA) published a scientific statement in Circulation detailing the current understanding of menopause transition (MT), its impact on the risk for postmenopausal cardiovascular disease (CVD), as well as early intervention strategies.
In the United States (US), the leading cause of death in women is CVD. The risk for CVD increases substantially following menopause, resulting in a later development of coronary heart disease (CHD) than in men. It has been hypothesized that MT may contribute to an elevated risk for CHD. Longitudinal studies of women in MT over the past 2 decades have enhanced understanding of the relationship between MT and CVD, and allowed investigators to unravel the impacts of chronological vs ovarian aging in terms of CVD risk. These studies indicate changes in sex hormone patterns, as well as adverse shifts in vascular health, body composition, and levels of lipids and lipoproteins, all of which can contribute to an increased risk for postmenopausal development of CVD.
With this statement, AHA sough to provide an update to its most recent guidelines on prevention of CVD in women issued in 2011.
MT is defined as the progression from regular menstruation to the absence of menses and is often characterized by the advent of variable menstrual cycles. During this period, several significant physiological changes (eg, hormonal, menstrual) occur that can have an impact on the risk for CVD.
Natural menopause occurs at a median age of 50 years, with “premature” and “early” menopause occurring before the age of 40 years and between 40 and 45 years, respectively. With US life expectancy on the rise, many women are expected to be postmenopausal for up to 40% of their lives.
Earlier age at menopause onset has been associated with a higher CVD risk and linked with low parity, short menstrual cycle length, smoking, Black or Hispanic ethnicity, and poorer CV health profile during reproductive years.
Menopause occurring as a result of bilateral oophorectomy, has been associated with a greater risk for CVD, but hysterectomy, performed before or after menopause, was not found to have an impact on CVD risk. The North American Menopause Society recommends menopause hormone therapy (MHT) for women with premature or early menopause – natural or surgical – until at least age 50 years.
The presence of vasomotor symptoms (eg, hot flashes, night sweats) during MT was found to predict greater CVD risk and may indicate subclinical atherosclerosis. The incidence of depression was found to increase during peri- and post-menopause and to be linked to vasomotor symptoms and incident CVD. Sleep disturbance, which is commonly reported during MT, was found to be associated with an elevated risk for subclinical CVD and poorer CV health indices.
During perimenopause, women are particularly vulnerable to the multiple cardiometabolic and vascular alterations that occur throughout MT and have been associated with increased CVD risk.
Changes in the volumes and locations of body fat are another hallmark of MT. Although lean muscle mass is reduced, central/visceral fat deposits become more pronounced. This increase in central adiposity has been linked to a higher mortality risk, regardless of body mass index (BMI). Pericardial fat volume also increases postmenopausally, independent of age. This change in pericardial fat may be modulated by MHT use or estradiol levels.
Although levels of low-density lipoprotein-C and apolipoprotein B are increased during midlife, the risks for vascular remodeling and metabolic syndrome are thought to result from MT rather than aging. Other changes that occur in midlife (eg, increases in blood pressure and glucose and insulin levels) are more likely to be related to chronological aging. Increases in levels of high-density lipoprotein (HDL) during MT have been associated with greater CVD risk.
Recommendations for a healthy diet and regular exercise are thought to be followed by <20% and <10% of menopausal women, respectively. For women with suboptimal health metrics during MT, a multidimensional lifestyle intervention may be effective for preventing weight gain and reducing levels of glucose, insulin and triglyceride, as well as systolic and diastolic blood pressure and subclinical atherosclerosis. Despite strong observational evidence indicating that MT is a period of elevated CVD risk, randomized controlled trials have yet to adequately represent this high-risk population.
Further research into the impact on cardiometabolic status on initiation, duration, and type and route of administration of MHT is needed to better inform recommendations. In addition, more research is also needed to better understand the impact of lipid-lowering medications on the primary and secondary prevention of atherosclerosis and patient survival in menopausal women, to formulate sex-specific guidelines.
Healthcare practitioners are advised to recommend an aggressive preventive approach for women during MT (including weight reduction and skeletal muscle mass maintenance), in order to reduce CVD risk and mitigate adverse cardiometabolic changes.
“The reported findings underline the significance of MT as a time of accelerating CVD risk, thereby emphasizing the importance of monitoring women’s health during midlife, a critical window for implementing early intervention strategies to reduce CVD risk,” noted the statement authors.
Funding and Conflicts of Interest Disclosures
Please see original article for all disclosures.
Khoudary SRE, Aggarwal B, Beckie TM, 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:e1-e27. doi:10.1161/cir.0000000000000912