New data from a large US population-based cohort study highlighted uterine fibroids as a potential signal of increased long-term risk for atherosclerotic cardiovascular disease, particularly in women younger than 40 years.

Specifically, results showed women with fibroids had a higher risk for coronary artery disease, cerebrovascular disease, and peripheral artery disease at 10 years than those who did not have fibroids.

The analysis, which was published in the Journal of the American Heart Association, included 450,177 women with fibroids and 2,250,885 matched control individuals using Optum’s Clinformatics Data Mart from 2000 to 2022. More than 2.7 million women contributed data, with a mean age of 41 years; none had atherosclerotic cardiovascular disease at baseline.

Participants were followed for up to 10 years. Investigators applied pooled logistic regression and multiple inverse probability weights to balance cardiovascular, metabolic, reproductive, and mental health-related confounders and to account for disenrollment and incident fibroid diagnoses among control individuals.

Atherosclerotic cardiovascular disease endpoints included coronary artery disease, cerebrovascular disease, peripheral artery disease, myocardial infarction, ischemic stroke, transient ischemic attack, and angina. Researchers identified events using validated International Classification of Diseases, Current Procedural Terminology, and Healthcare Common Procedure Coding System coding algorithms.

Notable and Persistent Cardiovascular Risk

At 1 year, women with fibroids had a 2.47-fold higher adjusted risk for atherosclerotic cardiovascular disease than control individuals. By 10 years, elevated risk remained (adjusted risk ratio [aRR], 1.81; 95% CI, 1.66-1.96), with cumulative incidence reaching 5.42% among those with fibroids vs 3.00% in control individuals.

At 10 years, event rates were higher across every atherosclerotic cardiovascular disease outcomes:

• Coronary artery disease (aRR, 1.61; 95% CI, 1.42-1.82)
• Cerebrovascular disease: (aRR, 1.77; 95% CI, 1.55-2.01)
• Peripheral artery disease (aRR, 1.90; 95% CI, 1.45-1.20)
• Ischemic stroke (aRR, 1.66; 95% CI, 1.35-2.02)
• Myocardial infarction (aRR, 1.50; 95% CI, 1.18-1.89)

Risk differences widened over time. For atherosclerotic cardiovascular disease overall, the adjusted risk difference increased from 0.41 percentage points at 1 year to 2.40 percentage points at 10 years.

The largest effect size was seen in women younger than 40 years. In this group, the 10-year adjusted atherosclerotic cardiovascular disease RR reached 3.51 — more than triple that of matched control individuals — and the risk difference exceeded 4 percentage points.

Associations were consistent across racial and ethnic groups, but the researchers noted some differences in subgroup analyses. The relative risk between those with uterine fibroids and matched control individuals was lowest among Black women, though the absolute risk differences was largest. And, relative risk was highest at several time points for Asian women, except for 10 years, when the risk was highest among Hispanic women.

Measurement-error analyses examining possible underdiagnosis of obesity or fibroids did not substantially alter outcomes. Bias-adjusted estimates remained directionally stable.

The consistent findings across the study’s multiple analyses suggest that uterine fibroids may serve as an important clinical marker for elevated cardiovascular risk, the researchers concluded.

Why Fibroids May Influence Heart Health

Fibroids produce inflammatory cytokines and chemokines that may circulate systemically, contributing to endothelial dysfunction, oxidative stress, and vascular remodeling. These biologic pathways closely overlap with those implicated in atherosclerosis, offering a plausible mechanistic explanation for the observed association, the researchers wrote.

Ayman Al-Hendy, MD, PhD, professor and vice chair in the Department of Obstetrics and Gynecology at the University of Chicago, Chicago, who was not involved with the study, placed the findings in context.

“Having uterine fibroids clearly increases the risk of atherosclerotic cardiovascular disease. This used to be considered a mere epidemiological association or possibly thought to reflect shared risk factors. However, innovative recent work demonstrates that pro-inflammatory factors are profusely secreted from uterine fibroids and can reach systemic circulation, potentially contributing to morbidities in distant organs such as the cardiovascular system,” he said in an interview.

With atherosclerotic cardiovascular disease remaining the leading cause of death among women, the findings highlight an opportunity for earlier cardiovascular risk assessment and preventive strategies in patients diagnosed with uterine fibroids.

“Women’s cardiovascular health has been historically understudied, so increased visibility for this work is crucial. We hope this attention will catalyze further investigation into female-specific cardiovascular risk factors and ultimately improve prevention and care for women at risk of heart disease,” lead study author Julia D. DiTosto, a PhD candidate in epidemiology at Perelman School of Medicine, University of Pennsylvania, Philadelphia, told Medscape Medical News.

The study was supported by the Patient-Centered Outcomes Research Institute and the National Heart, Lung, and Blood Institute. Al-Hendy reported no relevant conflicts of interest. DiTosto reported no relevant conflicts of interest.

Lois Anzelowitz Levine is a medical writer who has written for Dermatology Times, Infection Control Today, and Contemporary Pediatrics, among other journals. She is based in Dallas.