Cardiovascular events associated with PCOS diagnosis in large longitudinal cohort

Abstract

OBJECTIVE: Polycystic ovarian syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is associated with cardiometabolic comorbidities. Information on cardiovascular disease (CVD) event risk associated with PCOS is mixed limited by sample size, diagnostic criteria, and years of follow up especially in US cohorts. Metformin, a drug traditionally used to treat patients with type 2 diabetes (T2D), is first line treatment for many women with PCOS We hypothesize that women with PCOS are at increased risk for developing cardiovascular diseases CVD and that metformin may play a protective role in disease progression. METHODS: We leveraged the Penn Medicine electronic health record (EHR) which contains diagnosis information for 2,514,400 women. We calculated relative risk (RR) of being diagnosed with CVD or thrombotic disease (based on diagnosis codes) for women who were also diagnosed with PCOS or PCOS + T2D. For both RR calculations, our cases were women aged 15-50 who had at least one visit with PCOS diagnosis with or without T2D diagnosis. Controls were women aged 15-50 without a PCOS diagnosis but who had at least one visit for T2D. We also calculated RR of being diagnosed with CVD or thrombotic event for women aged 15-50 with at least one PCOS + T2D diagnosis who were treated with the drug metformin. Controls were women aged 15-50 with a PCOS +T2D diagnosis but were not treated with metformin. RESULTS: Of the 945,670 women aged 15-50, 22,030 (2.3%) had at least one visit for PCOS diagnosis while 2,010 (0.2%) had PCOS and T2D. We found that the risk for CVD for women with PCOS was 1.35 times that of age matched controls (95% CI 1.29 ± 1.43, p = 1.76e-28) and the risk for thrombotic disease was 2.02 times that of age matched controls (95% CI 1.81 ± 2.26, p = 5.25e-37). We found that women with PCOS + T2D had decreased risk for CVD (RR = 0.26, 96% CI 0.23 ± 0.29, p = 6.21e-140) and thrombotic disease (RR = 0.60, 95% CI 0.47 ± 0.77, p = 3.02e-05). Because many women with T2D are prescribed metformin, we wanted to know if a metformin prescription had a protective effect on being diagnosed with CVD or thrombotic disease. By calculating RR, we found that women with PCOS + T2D who were prescribed metformin were 15% less likely of developing CVD (RR = 0.85, 95% CI 0.77 ± 0.93, p = 5.03e-05) and 4% less likely of developing TD (RR = 0.96, 95% CI 0.83 ± 1.12, NS) compared to patients that were never prescribed metformin. CONCLUSIONS: In a large longitudinal cohort of women diagnosed with PCOS, we showed that a PCOS diagnosis was associated with an increased risk of CVD events. We also showed that PCOS patients who also had T2D diagnosis had decreased risk of CVD, which we observed was potentially associated by the protective effects of the drug metformin. Due to the high prevalence of CVD in women, longitudinal studies are needed to uncover the molecular, genetic, and pharmacogenomic pathways underlying disease progression in women with PCOS.