Analyses of prospectively collected data from participants in the Nurses’ Health Study II (NHS II) show that laparoscopically confirmed endometriosis is associated with an increased risk for subsequent development of coronary heart disease (CHD). The finding of increased risk was robust across multiple CHD endpoints and found to be highest among young women.
Fan Mu, ScD, lead author of the published article,1 was involved in the study as a graduate student at Harvard T.H. Chan School of Public Health, Boston. She told Contemporary OB/GYN, “Endometriosis has been associated with systemic chronic inflammation, heightened oxidative stress, and an atherogenic lipid profile, all of which may increase a women’s risk for CHD. However, to our knowledge, ours is the first study to explore an association between endometriosis and CHD risk.”
“Practitioners should be aware that women with endometriosis may be at higher risk for heart disease compared to women without endometriosis, and that this increased risk may be highest among young women. Based on our findings, we believe it is important that practitioners promote heart healthy lifestyle habits among women with endometriosis, even young women, and screen them for heart disease that remains the leading cause of death in women,” said senior study author Stacey Missmer, ScD, Director of Epidemiologic Research in Reproductive Medicine, Brigham and Women’s Hospital, Boston.
The NHS II enrolled 116,430 female nurses who were ages 25 to 42 years at study entry in 1989. After excluding women with a pre-enrollment history of myocardial infarction, stroke, angiographically confirmed angina, or coronary artery bypass graft surgery/coronary angioplasty/stent, the study investigating the association between endometriosis and CHD risk included 5,296 women with laparoscopically confirmed endometriosis and 109,161 women controls without endometriosis at study entry.
Incident cases of myocardial infarction, angiographically confirmed angina, and coronary artery bypass graft surgery/coronary angioplasty during 20 years of follow-up were identified. The risk of each of these events or for any of the CHD events as a combined endpoint was compared in the endometriosis and no endometriosis groups using multivariable Cox proportional hazards models controlling for known and hypothesized confounders.
The results showed that the risk for each of the endpoints was significantly increased among women with laparoscopically confirmed endometriosis, ranging from 1.35- to 1.91-fold compared with the control population. When women were stratified by age into four groups (<40, 40-50, 50-55, and ≥55 years), the increased risk for developing the combined endpoint was highest in the youngest group and decreased with increasing age. The increased risk for any CHD event comparing women with endometriosis to women without was more than 3-fold among women <40 years, 1.65-fold for women aged >40 to 50 years, and 1.44-fold for women aged >50 to 55 years. There was no significant increased risk of CHD among women ≥55 years old.
The investigators were also able to assess what proportions of the association between endometriosis and CHD were statistically accounted for by various treatment factors. Those analyses indicated that removal of the uterus or ovaries may account for a part of the increased risk.
“Surgically-induced menopause prior to natural menopause may increase risk of heart disease, and this elevated risk may be more evident at younger ages,” said Dr Mu.
Highlighting the strengths of the study, Dr Mu noted the ability to document a prospective association between surgically diagnosed endometriosis and subsequent risk of CHD based on its longitudinal design with 20 years of follow-up in a large population. In addition, the wealth of time-varying data allowed for detailed adjustment using multivariable Cox models and marginal structural models for known and suspected potential confounders and risk factors for CHD, she said, adding that minimal confounding was seen.
1. Mu F, et al. Endometriosis and risk of coronary heart disease. Circ Cardiovac Qual Outcomes. 2016;9:257–264.