BOSTON, MA — Endometriosis raised the summary risk for any coronary heart disease (CHD) by 62% overall and by a staggering 200% in women age 40 or younger in a Nurses' Health Study 2 analysis[1].

The association between endometriosis and CHD was consistent no matter how CHD was defined (MI, angina, or coronary bypass/angioplasty/stent).

"This [consistency] is one of those things that's great for science, but bad for women," senior author Dr Stacey Missmer (Brigham and Women's Hospital/Harvard University, Boston, MA) told heartwire from Medscape.

The association is not particularly surprising, however, because women with endometriosis are known to have systemic, chronic inflammation, an atherogenic lipid profile, heightened oxidative stress, and several overlapping risk factors for cardiovascular disease, she said.

Commenting on the findings, GoRed American Heart Association spokesperson Dr Suzanne Steinbaum (Women's Heart Health at Northwell Lenox Hill Hospital, New York) said, "It kind of blew me away. To my knowledge there's never been a study like this."

She pointed out that this is not a small population and that a number of other cutting-edge studies have recently made a connection between hormones and gynecologic history and the development of coronary artery disease.

Endometriosis is thought to affect about 10% of women of reproductive age in the US.

Part of why it's taken so long to pin down a relationship between endometriosis and CHD is the need for longitudinal data with accurately confirmed endometriosis and cardiovascular outcomes over time, Missmer said.

The group turned to the Nurses' Health Study 2 to evaluate outcomes in 116,430 female nurses followed from 1989 to 2009 in the prospective, longitudinal cohort. Laparoscopically confirmed endometriosis was present in 11,903 women, and 1438 CHD cases were reported over the 20-year follow-up.

Compared with women without endometriosis, women with endometriosis were 1.52 times more likely to have an MI, 1.91 times more likely to develop angiographically confirmed angina, and 1.35 times more likely to need CABG surgery, a coronary angioplasty procedure, or a stent.

The association was independent of several potential confounders, including use of oral contraceptives and hormone-replacement therapy, although details of other hormonal treatments for endometriosis could not be evaluated, according to the research, published online March 29, 2016 in Circulation: Cardiovascular Quality Outcomes, with first author Dr Fan Mu (previously with Brigham and Women's Hospital and now working in industry).

Women with endometriosis had a higher risk for any of the CHD end points combined (relative risk [RR] 1.62), with the risk threefold higher in women 40 and younger (RR 3.08). CHD risk was not increased in women older than 55 years (RR 0.98).

The authors hypothesize that endometriosis plays a larger role in young women who have not accumulated many of the known strong cardiovascular risk factors but still live with an illness that has that chronic inflammatory and oxidative stress-based states, Missmer explained.

A mediation analysis performed to determine whether the treatments women with endometriosis undergo, not the endometriosis itself, may be driving the association, found that 42% of the association between endometriosis and CHD could be explained by greater frequency of hysterectomy/oophorectomy and earlier age at surgery.

There have been three or four reports previously demonstrating a higher risk of cardiovascular disease with hysterectomy, although the biological underpinnings for this are not well understood, Missmer said.

"Very similar to querying about pregnancy history, the cardiologist does need to be aware of whether the woman has undergone surgical menopause, regardless of her age, and that surgical menopause may be conferring cardiovascular risk," she added.

Missmer said young women need a better understanding of heart disease and heart-healthy lifestyle choices but stopped short of recommending universal cardiology referrals.

Steinbaum disagreed. "In my opinion, when we see that a young woman has any of the risk factors, be it preeclampsia or endometriosis, that woman should be referred to a cardiologist, not for aggressive diagnostics, but for really [intensive] evaluation of their risk factors that we know are reversible in order to stay on top of them."

The biggest limitation of the study is that 94% of the women with endometriosis were white, yet minority women are known to be at greater risk for heart disease, Steinbaum said.

In the racially diverse INTERHEART study, she noted that 90% of the global risk for acute MI was preventable by addressing common risk factors such as exercise, diet, smoking, and alcohol intake.

"Prevention is the most critical piece of women in heart disease because once women get heart disease, their outcomes are significantly worse," Steinbaum said.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The Nurses' Health Study 2 is supported by Public Health Service grants from the National Cancer Institute, National Institutes of Health, and US Department of Health and Human Services. The authors and Steinbaum reported no relevant financial relationships.