Risk of Ischemic Heart Disease in Women with Dysmenorrhea: A Longitudinal Analysis of 251,264 Patients Across Three Diverse Cohorts

This study explores the role of dysmenorrhea as a sex-specific ischemic heart disease (IHD) risk enhancing factor across three large cohorts of 251,264 individuals, two retrospective electronic health records cohorts, i.e., the Mount Sinai Health System, All of Us, and one prospective cohort, the Australian Longitudinal Survey on Womens Health. Considering traditional and nontraditional young female-specific cardiovascular risk factors, hazard ratios for IHD were estimated through Cox regression models and propensity score matching, and dysmenorrhea was found to be significantly associated, with a 40% to 225% increase in the hazard of developing IHD. The risk was found to be higher in women of color and those with persistent dysmenorrhea beginning in adolescence. The addition of dysmenorrhea as a predictor beyond traditional cardiovascular risk scores improved risk stratification (AUROC 0.786 vs 0.798, p-value 0.02). Within the Mount Sinais electronic health records, we also found dysmenorrhea diagnostic codes to have a 37.3% false negative rate. To overcome the under-coding of the diagnosis, we implemented a large language model EHR-phenotyping algorithm which led to higher hazard ratios, together with self-reporting within the ALSWH (HR 2.5 and 3.3, respectively), compared to diagnostic code-only cohort definition (HR 1.5). These findings highlight the need to recognize dysmenorrheas impact beyond reproduction and call for greater clinical and research awareness.