Cardiovascular disease in a nationwide population of Danish women with polycystic ovary syndrome

Abstract

Background: Polycystic ovary syndrome (PCOS) is associated with obesity and low grade inflammation and the risk for cardiovascular disease (CVD) could be increased in PCOS.

Methods: National register-based study including women with PCOS and no previous diagnosis of CVD, hypertension, or dyslipidemia. PCOS Denmark (N = 18,112) included women with PCOS in the Danish National Patient Register. PCOS Odense University Hospital (OUH, N = 1165) was an embedded cohort including premenopausal women with PCOS and clinical and biochemical examination. Three age-matched controls were included per patient in PCOS Denmark (N = 52,769). The main study outcome was CVD events including hypertension and dyslipidemia defined according to nationwide in- and outpatient hospital contact diagnosis codes and/or inferred from filled medicine prescriptions.

Results: The age at inclusion was median (quartiles) 29 (23-35) years and follow up was 11.1 (6.9-16.0) years. The Hazard ratio (95% CI) for development of CVD in PCOS Denmark was 1.7 (1.7; 1.8) (P < 0.001) and the total event rate of CVD was 22.6 per 1000 patient years in PCOS Denmark vs. 13.2 per 1000 patient years in controls (P < 0.001). The median age at diagnosis of CVD was 35 (28-42) years in PCOS Denmark vs. 36 (30-43) years in controls (P < 0.001). Obesity, diabetes, and infertility, and previous use of oral contraceptives were associated with increased risk of development of CVD in PCOS Denmark (P < 0.001). Women in PCOS OUH resembled women in PCOS Denmark regarding risk of CVD. Age, BMI, blood pressure, lipid status, and glycemic status predicted development of CVD in PCOS OUH.

Conclusion: The event rate of CVD including hypertension and dyslipidemia was higher in PCOS compared to controls. The risk of developing CVD must be considered even in young women with PCOS.

Keywords: Cardiovascular disease; HT; ICD-10; Medicine prescriptions; Nationwide; Polycystic ovary syndrome; Register-based.

Fig. 1

Flowchart of included women with PCOS and controls. CVD was defined as at least one of the following criteria: (1) the presence of a CVD diagnosis in NPR according to ICD10: E78 (dyslipidemia), G45–G46 (TCI, stroke), I10–13 (essential hypertension and hypertension with complications), I20 (angina), I21–25 (myocardial infarction and ichemic coronary disease), I26 (lung embolism), I50 (incompensatio cordis), I63–I64 (cerebral infarction), I65–I66 (occlusion of vertebral and cerebral arteries), I80–82 (venous thrombosis) or (2) prescription of drugs for treatment of CVD according to the National Prescriptions Registry database: antithrombotics (B01), antihypertensives (C02: alpha-blockers, C07: beta-blockers, C08: calcium-antagonists, C09: renin-angiotensin blockers), C10: antilipids. Two or more medicine withdrawals should occur within the same ATC group to be included