Early Menopause Can Signal Cardiovascular Risk, Analysis Finds

Women who enter menopause before age 50 are substantially more likely to have a non-fatal cardiovascular event before they turn 60, and the risk grows the younger the women are when menstruation ends, according to an analysis of more than 300,000 patient records published last week in Lancet Public Health.¹

Led by Dongshan Zhu, a PhD candidate at the School of Public Health at the University of Queensland, Australia, the analysis draws on records from 15 studies, covering a period that stretched from 1946 to 2013. The team found that compared with women who reached menopause at age 50-51, those who entered menopause at younger ages had their highest risk of of cardiovascular events in the immediate years afterward, but this elevated risk disappeared after age 70. Compared with those who reached menopause at age 50, the study found:

• The hazard ratio (HR) (95% CI) for women who reached menopause prematurely, from age 45 to 49, was 1.12 (1.07-1.18); P <.0001.
• The HR (95% CI) for those who reached menopause early, from age 40 to 44 was 1.30 (1.22-1.39); P <.0001.
• The HR (95% CI) for those who reached menopause before age 40 was 1.55 (1.38-1.73); P <.0001.

The risk of a heart attack, stroke, or other cardiovascular event by age 60 was nearly double in the women who entered menopause prematurely (HR, 1.88; 95% CI, 1.62-2.20; P <.0001).

The pattern persisted even after researchers adjusted for body mass index (BMI) and smoking status, and was not affected by the use of postmenopausal hormone therapy.

In an accompanying editorial, authors Lizelle Bernhardt, MCur, of the Department of Cardiovascular Sciences, and Claire Lawson, PhD, of the Diabetes Research Centre, both of the University of Leicester in London, wrote that the findings have important clinical and public health implications.

“The doubling of cardiovascular disease risk before age 60 years who have premature menopause is concerning and indicates an urgent need to raise awareness of cardiovascular disease risk in younger women,” they wrote. Already, there is a perception that cardiovascular risk is mostly a problem for men, and “this sex bias needs to be addressed.”²

Additionally, they wrote, the work by Zhu and colleagues “underpins the importance of precision medicine across the cardiovascular disease life course.” More work is being done to understand the differences in heart disease between men and women—and major professional organizations of cardiologists are working to address shortages of female cardiologists.

While the American College of Cardiology and the American Heart Association have aggressively updated prevention guidelines in the past year, the shift away from a “one size fits all” approach is essential to move toward more customized primary and secondary prevention guidelines, Bernhardt and Lawson said, “to target the increasing global burden of cardiovascular disease.

References

1. 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 [published online October 3, 2019]. Lancet Public Health. doi: 10.1016/S2468-2667(19)30155-0.

2. Bernhardt L, Lawson CA. Early menopause and risk of cardiovascular disease: an issue for young women [published online October 3, 2019]. Lancet Public Health. doi: 10.1016/2468-2667(19)30184-7.