Polycystic Ovarian Syndrome and the Long-Term Risk of Arrhythmias

Abstract

BACKGROUND: Polycystic ovarian syndrome (PCOS) is associated with increased cardiovascular morbidity and a higher risk of atherosclerotic cardiovascular disease. PCOS has been associated with electrocardiographic alterations. However, the potential long-term risk of cardiac arrhythmias in women with PCOS remains insufficiently investigated. METHODS: Women diagnosed with PCOS in Denmark (1977–2024) were matched on age and year of index with female controls from the background population (ratio 1:4). The primary outcome was incident arrhythmia, with subtype of arrhythmia and cardiac implantable electronic device (CIED, ie, pacemaker and cardioverter defibrillator implantation) implantation as secondary outcomes. Patients were followed from date of PCOS diagnosis until date of event, emigration, death, or end of study (January 31, 2024). RESULTS: The study included 26 728 women with PCOS (median age, 27.8 years [interquartile range, 23.7–32.1]) and 106 912 controls. Women with PCOS had a higher comorbidity burden and pharmacotherapy use compared with controls. The 25-year associated risk of arrhythmias was higher among women with PCOS (6.3% [95% CI, 5.6–6.9]) compared with controls (4.2% [95% CI, 3.9–4.5]), equivalent to incidence rates of 23.8 (95% CI, 22.1–25.6) and 15.7 (95% CI, 15.0–16.4) per 10 000 person-years, respectively, an unadjusted hazard ratio (HR) of 1.56 (95% CI, 1.43–1.71), and an adjusted HR of 1.48 (95% CI, 1.35–1.63). Across subtypes of arrhythmias, women with PCOS were associated with a higher risk of advanced atrioventricular block (adjusted HR, 1.76 [95% CI, 1.05–2.93]), cardiac arrest (adjusted HR, 1.44 [95% CI, 1.03–2.08]), and atrial fibrillation or flutter (adjusted HR, 1.44 [95% CI, 1.20–1.73]) compared with controls. Women with PCOS were more likely to receive a CIED compared with controls (incidence rates of 1.9 [95% CI, 1.5–2.5] and 1.1 [95% CI, 0.9–1.3] per 10 000 person-years, respectively; adjusted HR, 1.85 [95% CI, 1.30–2.63]). The higher associated risk of arrhythmias and likelihood of receiving a CIED among women with PCOS was independent of use of metformin, oral contraception, spironolactone, antiandrogens, and glucagon-like peptide receptor analogs. CONCLUSIONS: Women with PCOS had a higher associated long-term risk of developing arrhythmias and a higher incidence of receiving a CIED compared with female controls from the background population. Despite low absolute event rates, these findings emphasize the clinical relevance of early cardiovascular risk assessment and preventive strategies for patients diagnosed with PCOS.