BACKGROUND Polycystic ovary syndrome (PCOS) is associated with cardiometabolic disease, but recent systematic reviews and meta-analyses of longitudinal studies that quantify these associations are lacking. OBJECTIVE AND RATIONALE Is PCOS a risk factor for cardiometabolic disease? SEARCH METHODS We searched from inception to September 2019 in MEDLINE and EMBASE using controlled terms (e.g. MESH) and text words for PCOS and cardiometabolic outcomes, including cardiovascular disease (CVD), stroke, myocardial infarction, hypertension (HT), type 2 diabetes (T2D), metabolic syndrome and dyslipidaemia. Cohort studies and case–control studies comparing the prevalence of T2D, HT, fatal or non-fatal CVD and/or lipid concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) between women with and without PCOS of ≥18 years of age were eligible for this systematic review and meta-analysis. Studies were eligible regardless of the degree to which they adjusted for confounders including obesity. Articles had to be written in English, German or Dutch. Intervention studies, animal studies, conference abstracts, studies with a follow-up duration less than 3 years and studies with less than 10 PCOS cases were excluded. Study selection, quality assessment (Newcastle–Ottawa Scale) and data extraction were performed by two independent researchers. OUTCOMES Of the 5971 identified records, 23 cohort studies were included in the current systematic review. Women with PCOS had increased risks of HT (risk ratio (RR): 1.75, 95% CI 1.42 to 2.15), T2D (RR: 3.00, 95% CI 2.56 to 3.51), a higher serum concentration of TC (mean difference (MD): 7.14 95% CI 1.58 to 12.70 mg/dl), a lower serum concentration of HDL-C (MD: −2.45 95% CI −4.51 to −0.38 mg/dl) and increased risks of non-fatal cerebrovascular disease events (RR: 1.41, 95% CI 1.02 to 1.94) compared to women without PCOS. No differences were found for LDL-C (MD: 3.32 95% CI −4.11 to 10.75 mg/dl), TG (MD 18.53 95% CI −0.58 to 37.64 mg/dl) or coronary disease events (RR: 1.78, 95% CI 0.99 to 3.23). No meta-analyses could be performed for fatal CVD events due to the paucity of mortality data. WIDER IMPLICATIONS Women with PCOS are at increased risk of cardiometabolic disease. This review quantifies this risk, which is important for clinicians to inform patients and to take into account in the cardiovascular risk assessment of women with PCOS. Future clinical trials are needed to assess the ability of cardiometabolic screening and management in women with PCOS to reduce future CVD morbidity.

Based on the current available evidence, follow-up is only recommended for women with a history of preeclampsia. For all reproductive and pregnancy-related disorders optimisation of modifiable cardiovascular risk factors is recommended to reduce the risk of future CVD.

C ardiovascular diseases (CVD) are the primary cause of death in women. 1 In the past decade, it has become clear that there is a strong relation of common complications of pregnancy, such as hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), with future CVD events in women. [2][3][4][5][6] The findings have been acknowledged by the American Heart Association 2011 in its Guidelines on the Prevention of Cardiovascular Disease in Women, which stipulate that healthcare professionals should obtain pregnancy history as part of routine clinical intake and evaluate cardiovascular risk factors.1 Moreover, in the guidelines for the prevention of stroke in women, the American Heart Association recommends that women with preeclampsia should be evaluated 6 months to 1 year postpartum to assess and treat potential cardiovascular risk factors, including hypertension, obesity, smoking, and dyslipidemia. 7A considerable proportion of women develop a complication of pregnancy. GDM affects as much as 5% to 9% of pregnancies, 8 whereas ≈10% of pregnancies are complicated by high blood pressure. 9,10 The latter can be subdivided into preeclampsia and pregnancy-induced hypertension. Although these conditions generally subside after delivery, many of these women are predisposed to develop future type 2 diabetes mellitus (T2D), hypertension, and CVD. [11][12][13][14][15][16][17] As most studies focused on the risk of developing these cardiovascular risk factors, little is known about the time frame (years after the pregnancy) in which a woman with a history of HDP or GDM develops T2D and hypertension. [11][12][13][14][15][16][17] This information is of importance for the timing of effective screening programs to reduce the risk of CVD in women with these complications of pregnancy. Furthermore, it is unknown whether complications of pregnancy are independently associated with the risk Abstract-A prospective cohort study was conducted to assess the impact of a history of hypertensive disorder of pregnancy (HDP) or gestational diabetes mellitus (GDM) on the risk and age of onset of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease (CVD) later in life, independent of hypertension and T2D. Between 1993 and 1997, 22 265 ever-pregnant women were included from the European Prospective Investigation into Cancer and Nutrition-NL study, aged 20 to 70 years at baseline. Details on complications of pregnancy and known hypertension were obtained by questionnaire. Blood pressure was measured at enrollment. Participants were followed for the occurrence of CVD events. Data were analyzed using ANCOVA, multivariable logistic regression, and Cox proportional hazard (with HDP and GDM as time-dependent variables for T2D and CVD) models. At enrollment, women with a HDP reported diagnosis of hypertension 7.7 years earlier (95% confidence interval [CI] 6.9-8.5) and women with GDM reported diagnosis of T2D 7.7 years earlier (95% CI 5.8-9.6) than women without pregnancy complications. After adjustment fo...