Association of Polycystic Ovary Syndrome with patient and offspring cardiometabolic outcomes: a retrospective, observational study

Date of ISAC Approval: 
Lay Summary: 
Polycystic Ovary Syndrome (PCOS) is a common condition affecting 5-10% of young women. PCOS increases the risk of type 2 diabetes and is associated with a high prevalence of risk factors for cardiovascular disease (CVD). However, it is unclear whether this leads to an increased risk of angina, heart attack and stroke, or death from CVD. Recent studies have also suggested that children born to mothers with PCOS may also be more at risk of obesity and early puberty. In this study we wish to determine whether women with PCOS have an increased risk of death from CVD and/or an increased risk of angina, heart attack and stroke. We also wish to establish if there is an increased risk of excess weight and obesity amongst their children. To do this we wish to select patients from the Clinical Practice Research Datalink (CPRD) with a recorded diagnosis of PCOS and to match them with patients without PCOS by age, body mass index (BMI) and general practice. We will then follow these patients to compare the number who subsequently have recorded diagnoses of each of the conditions and also measure weight gain in their children. In so doing, we hope to establish whether women with PCOS and their children should be screened more intensively for CVD risk.
Technical Summary: 
The aim of the study is to determine if there is an increased risk of cardiovascular events and mortality in patients with Polycystic Ovary Syndrome (PCOS). Both Aurum and GOLD will be used. Aurum will provide sufficient statistical power to ascertain the primary outcome, whilst the smaller population in GOLD will be required to utilise the mother-baby link. The study population will comprise patients with a diagnosis of PCOS from the Clinical Practice Research Datalink (CPRD) based on either a primary care diagnosis using the Read code classification or an ICD-10 coding from secondary care Hospital Episodes Statistics. These patients will then be matched by age, body mass index and primary care practice to control subjects with no history of PCOS. Subjects will be linked to offspring using the CPRD family number. Primary outcomes will be the incidence of large vessel disease (defined by the first record of myocardial infarction, angina, stroke, or revascularisation) identified from either Read code in the CPRD Aurum dataset or ICD-10 code in the HES inpatient dataset. Secondary outcomes will be the incidence of overweight/obesity and premature adrenarche in the children of mothers with PCOS identified from CPRD GOLD. Rates of progression to each primary outcome will be presented and compared using Cox proportional hazard models (CPHM) adjusting for smoking status, Charlson Index, total number of contacts with the general practitioner in the year prior to the index date, and IMD quintile.
Health Outcomes to be Measured: 
Myocardial infarction, angina, stroke, revascularisation in women with PCOS; increased birth weight and obesity in off-spring, premature adrenarche in off-spring.

Aled Rees - Chief Investigator - Cardiff University
Aled Rees - Collaborator - Cardiff University
Dr Christopher Morgan - Collaborator - Pharmatelligence
Mr Thomas Berni - Collaborator - Pharmatelligence
Mr Thomas Berni - Corresponding Applicant - Pharmatelligence

HES Admitted;HES Outpatient;Mother Baby Link;ONS;Patient IMD;Pregnancy Register