Uterine Fibroids Increase Future Risk of ASCVD For Up to 10 Years

Women with uterine fibroids, compared with those without the benign gynecological tumors, have a greater risk of developing atherosclerotic cardiovascular disease (ASCVD) up to 10 years down the line, according to data from a US-based cohort study.

It’s known that uterine fibroids and ASCVD share biological pathways, but less certain is whether this relationship heightens vulnerability to ASCVD, Julia D. DiTosto, MS (University of Pennsylvania, Philadelphia), and colleagues note in their paper. These new results, they say, “highlight the need for targeted ASCVD prevention among individuals with fibroids.”

Many prior studies on the topic have been cross-sectional, simultaneously assessing the two conditions and accompanying risk factors, DiTosto noted to TCTMD. “If we want to see whether or not fibroids may lead to cardiovascular disease, it sounds obvious, but we need to make sure the fibroids are occurring earlier in time. . . . Our study, I believe, is the first to prospectively look at cardiovascular disease events after having a fibroid diagnosis.”

The study leveraged a large administrative claims database as a way to maintain statistical power despite “the baseline event rate for reproductive aged women experiencing cardiovascular disease being quite low,” she added.

The investigators, DiTosto said, were “definitely surprised by the strength of the association that we found, in particular how that seemed to sustain even 10 years after diagnosis.”

Although their findings bolster the idea of a direct relationship between uterine fibroids and ASCVD, much more needs to be understood about mechanisms before implementing this knowledge in clinical practice, she cautioned. Future research may shed light on whether a fibroid diagnosis would be a helpful addition to existing risk calculators, but that’s not yet certain. Nor is it clear which interventions or therapies might help mediate the rise in ASCVD risk for women with these tumors.

The association between the two conditions may point to causality or fibroids may simply be a marker of higher cardiovascular risk. Either way, the information is useful, DiTosto said.

“Even if we’re not able to establish causality, identifying women who are at a higher risk is important, especially considering how large of a burden cardiovascular disease is in our country and it being the leading cause of morbidity and mortality among women,” she stressed.

Even if we’re not able to establish causality, identifying women who are who are at a higher risk is important. Julia DiTosto

DiTosto et al used Optum’s Clinformatics Data Mart resource to identify 450,177 women diagnosed with uterine fibroids between 2000 and 2022. They matched these individuals to 2,250,885 controls who had an annual gynecologic claim but not a fibroid diagnosis. Mean age at baseline was 41 years, with average follow-up of 5.18 years in the fibroid group and 4.02 years in the control group.

Women who had uterine fibroids experienced 6.45 ASCVD events per 1,000 person-years, as compared with 2.99 such events per 1,000 person-years among matched controls.

At both 1 year and 10 years, women with fibroids had more incident ASCVD (a composite of coronary artery, cerebrovascular, and peripheral artery disease) than controls. The elevations in risk persisted after adjustment for numerous potential confounders including race/ethnicity, age, smoking, comorbidities, parity, hypertensive disorders of pregnancy, gestational diabetes, polycystic ovary syndrome, infertility, oral contraceptives, depression, anxiety, cancer, and having had a recent annual physical exam, as well as various forms of medical therapy.

Risk of Incident ASCVD With vs Without Uterine Fibroids

With uterine fibroids, risk of incident ASCVD was consistently elevated for each of the endpoint’s individual components and among subgroups defined by race/ethnicity and age. The link between fibroids and ASCVD was strongest for women younger than 40.

The two conditions share numerous “pathophysiologic processes involving smooth muscle proliferation, fibrosis, calcification, and systemic inflammation [that] provide a plausible biologic foundation for the observed association,” the researchers explain. “Fibroids may overproduce inflammatory mediators, which can enter systemic circulation, promoting chronic inflammation, endothelial dysfunction, oxidative stress, and pro-atherosclerotic pathways, ultimately increasing ASCVD risk.”

They highlight the fact that their study involved women whose fibroids were “severe enough to warrant medical attention and healthcare encounters, rather than all fibroids including asymptomatic cases.”

Next up, it will be important to confirm these results across different populations and look into how ASCVD risk might vary by fibroid characteristics (size, number, and location), the researchers say. “Additionally, future research should examine the impact of fibroid removal procedures, such as hysterectomy, myomectomy, on cardiovascular outcomes to determine whether surgical intervention modifies the association between fibroids and ASCVD risk.”

DiTosto said that, as an epidemiologist, she’s hesitant to give clinical advice. That said, “I do think we have growing evidence that reproductive health . . . may provide important insights into cardiovascular health, [so] it could be important for these patients’ doctors to keep this in mind,” she suggested.