Summary
Shin et al. [1] performed a study that aimed to examine the association of premature menopause and age at menopause with the risk of heart failure (HF) and atrial fibrillation (AF). For this, a total of 1,401,175 postmenopausal women, who had undergone health examination provided by the Korean National Health Insurance Service, were included, and their reproductive histories were collected. The authors employed multivariable Cox proportional hazard models to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HF and AF, according to the history of premature menopause and age at menopause. After a mean follow-up of 9.1 years, there were 42,699 (3.0%) and 44,834 (3.2%) new cases of HF and AF, respectively. Women with history of premature menopause had an increased risk of HF (HR: 1.33, 95% CI: 1.26-1.40) and AF (HR: 1.09, 95% CI: 1.02-1.16), compared to women without the history. Compared to women aged ≥50 years at menopause, those who had menopause at ages 45-49, 40-44, and <40 years showed a significantly increased trend in HRs for the incident risk of both HF and AF (P for trend <0.001). The robustness of the results of a series of sensitivity analyses further strengthened the main findings. The authors suggest that postmenopausal women with a history of premature menopause or early age at menopause may have an increased risk of HF and AF. These reproductive factors need to be considered for preventing the future risk of HF and AF.
Commentary
The association between premature menopause and cardiovascular disease (CVD) risk, particularly HF and AF, has been increasingly recognised in the literature. The study presents compelling evidence linking premature menopause with an increased risk of HF and AF among postmenopausal women. This aligns with findings from the Multi-Ethnic Study of Atherosclerosis, which observed that later age at menopause is protective against HF [2], and with meta-analyses of observational data indicating that early menopause (before age 45) is associated with an increased risk of HF and AF [3].
Moreover, this study adds nuance understanding by showing a dose-response relationship, where the risk of HF and AF progressively increases as the age at menopause decreases. This is consistent with the biological understanding that the loss of endogenous estrogen, which occurs earlier in women with premature menopause, may lead to adverse cardiovascular remodelling, increased arterial stiffness, and a pro-inflammatory state, all contributing to the pathogenesis of HF and AF [4,5].
Importantly, the study also highlights that the association between premature menopause and cardiovascular outcomes is more pronounced in specific subgroups, such as younger women, non-smokers, and those with obesity. These findings suggest that reproductive history, including age at menopause, should be integrated into cardiovascular risk assessments, particularly in these higher-risk groups. Current guidelines, such as those from the American Heart Association, acknowledge premature menopause as a risk-enhancing factor for CVD, but this study underscores the need for its inclusion in routine clinical practice [6].
In conclusion, this study adds to the growing body of evidence that premature menopause is a critical determinant of female cardiovascular health. Given the observed dose-response relationship, it is imperative that clinicians consider reproductive factors when evaluating CVD risk and implement strategies to mitigate these risks in women who experience early menopause.
Take home key points
- The risk of heart failure and atrial fibrillation intensifies as the age at menopause decreases, with a particularly strong association observed in younger women, non-smokers, and those with obesity.
- The findings of the commented study are consistent with existing evidence and suggest that the loss of estrogen plays a central role in the development of these cardiovascular conditions.
- Reproductive history, including age at menopause, should be routinely considered in cardiovascular risk assessments for women.
Rakib Islam, MPH, PhD
Women’s Health Research Program, School of Public Health and Preventive Medicine, Monash University, Australia
References
- Shin J, Han K, Jung JH, et al. Age at menopause and risk of heart failure and atrial fibrillation: a nationwide cohort study. Eur Heart J. 2022;43(40):4148-4157.
https://pubmed.ncbi.nlm.nih.gov/36239217/ - Ebong IA, Watson KE, Goff DC Jr, et al. Age at menopause and incident heart failure: the Multi-Ethnic Study of Atherosclerosis. 2014;21(6):585-591.
https://pubmed.ncbi.nlm.nih.gov/24423934/ - Liu J, Jin X, Chen W, Wang L, Feng Z, Huang J. Early menopause is associated with increased risk of heart failure and atrial fibrillation: A systematic review and meta-analysis. 2023;176:107784.
https://pubmed.ncbi.nlm.nih.gov/37454569/ - Zhu D, Chung HF, Dobson AJ, et al. Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data. Lancet Public Health. 2019;4(11):e553-e564.
https://pubmed.ncbi.nlm.nih.gov/31588031/ - Ryczkowska K, Adach W, Janikowski K, Banach M, Bielecka-Dabrowa A. Menopause and women’s cardiovascular health: is it really an obvious relationship? Arch Med Sci. 2022;19(2):458-466.
https://pubmed.ncbi.nlm.nih.gov/37034510/ - El Khoudary SR, Aggarwal B, Beckie TM, et al.; 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. Circulation. 2020;142(25):e506-e532.
https://pubmed.ncbi.nlm.nih.gov/33251828/ -
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