Stefanie Hinkle

Association Between Uterine Fibroids and Risk of Atherosclerotic Cardiovascular Disease

Background Uterine fibroids and atherosclerotic cardiovascular disease (ASCVD) share biological pathways, yet whether risk of ASCVD is different among those with fibroids compared with those without remains unexplored in large US cohorts with longitudinal data. This study assessed the association between uterine fibroids and risk of incident ASCVD. Methods A US population‐based cohort study was done using Optum’s de‐identified Clinformatics Data Mart Database (2000–2022). Follow‐up continued until an ASCVD event, disenrollment, incident fibroid diagnosis in controls, or June 30, 2022. Individuals with fibroids were exact age‐matched (1:5) to individuals without fibroids with an annual gynecologic claim. Incident ASCVD, a composite of coronary artery disease, cerebrovascular disease, and peripheral artery disease, was evaluated, including individual events (eg, myocardial infarction and ischemic stroke). Results Among 450 177 individuals with fibroids and 2 250 885 controls (mean age: 41 years, SD 6.3), the 1‐year and 10‐year cumulative incidence (95% CI) of ASCVD was 0.74% (0.71–0.77) and 5.42% (5.18–5.67) for the fibroid group versus 0.30% (0.29–0.31) and 3.00% (2.90–3.11) for controls. Adjusted analyses showed an increased ASCVD risk in the fibroid group (1‐year risk ratio: 2.47 [95% CI, 2.32–2.61]; 1‐year risk difference, 0.41% [95% CI, 0.40–0.47]; 10‐year risk ratio, 1.81 [95% CI, 1.66–1.96]; 10‐year risk difference, 2.40% [95% CI, 2.07, 2.77]. The increased risk was consistent for all individual components of ASCVD. Results were consistent across race and ethnicity and age subgroup analyses and sensitivity analyses addressing measurement error. Conclusions Uterine fibroids are associated with sustained increased ASCVD risks up to 10 years postdiagnosis, supporting targeted ASCVD prevention in this population.

The Invisible Burden: Examining the Impact of Exposure Misclassification in Epidemiologic Analyses of Uterine Fibroids

ABSTRACT Background Uterine fibroids, a common gynaecologic condition, are often underdiagnosed, potentially biasing results in epidemiologic studies due to measurement error. Objectives To examine how varying sensitivity in detecting uterine fibroids impacts effect estimates, using the association with hypertension onset as an example. Methods Three simulation studies were conducted ( N  = 100,000), considering true population prevalences of uterine fibroids of 5%, 20% and 60%. The first study varied detection sensitivity between 0% and 100%. The second examined differential sensitivity by symptom status (asymptomatic vs. symptomatic). The third assessed differential sensitivity by racialised groups. Specificity remained fixed at 90%, and true risk ratios (RRs) for the association with hypertension were set at 1.3 and 1.8. Results Decreasing sensitivity biased results towards the null, with low‐sensitivity methods (e.g., self‐report) showing the largest bias and high‐sensitivity methods (e.g., transvaginal ultrasonography) the least bias. At low fibroid prevalence (5%), even gold‐standard ascertainment introduced bias due to imperfect specificity, whereas this concern diminished at higher prevalence. Assuming a dose–response relationship between fibroids and hypertension based on symptom status, results remained biased towards the null unless sensitivity was 100% and prevalence was high (60%); bias was most pronounced at low prevalence. When only symptomatic fibroids were associated with hypertension, increasing sensitivity biased results away from the null by capturing more asymptomatic cases. Studies using low‐sensitivity methods may fail to identify a true effect among Black females while identifying it among White females, potentially exacerbating disparities. Detection bias, where those with fibroids are more likely to have hypertension detected, could result in bias away from the null. Conclusions Underdiagnosis of uterine fibroids can bias results towards the null, particularly with self‐report or modest effect estimates, potentially obscuring true effects. When only symptomatic fibroids were associated with the outcome, the bias was away from the null. Results varied by symptom status and race, highlighting the need to prioritise sensitive ascertainment methods, employ sensitivity analyses and improve reliability across diverse gynecologic conditions and health disparities.