Women With Polycystic Ovary Syndrome Have an Increased Risk of Major Cardiovascular Events: a Population Study.

CONTEXT: The effects of polycystic ovary syndrome (PCOS) on cardiovascular morbidity and mortality are unclear. OBJECTIVE: This work aims to establish the relative risk of myocardial infarction (MI), stroke, angina, revascularization, and cardiovascular mortality for women with PCOS. METHODS: Data were extracted from the Clinical Practice Research Datalink Aurum database. Patients with PCOS were matched to controls (1:1) by age, body mass index (BMI) category, and primary care practice. The primary outcome was the time to major adverse cardiovascular event (MACE); a composite end point incorporating MI, stroke, angina, revascularization and cardiovascular mortality. Secondary outcomes were the individual MACE end points. RESULTS: Of 219 034 individuals with a diagnosis of PCOS, 174 660 (79.7%) met the eligibility criteria and were matched. Crude rates of the composite end point, MI, stroke, angina, revascularization, and cardiovascular mortality were respectively 82.7, 22.7, 27.4, 32.8, 10.5, and 6.97 per 100 000 patient-years for cases, and 64.3, 15.9, 25.7, 19.8, 7.13, and 7.75 per 100 000 patient-years for controls. In adjusted Cox proportional hazard models (CPHMs), the hazard ratios (HRs) were 1.26 (95% CI, 1.13-1.41), 1.38 (95% CI, 1.11-1.72), 1.60 (95% CI, 1.32-1.94), and 1.50 (95% CI, 1.08-2.07) for the composite outcome, MI, angina, and revascularization, respectively. In a time-dependent CPHM, weight gain (HR 1.01; 1.00-1.01), prior type 2 diabetes mellitus (T2DM) (HR 2.40; 1.76-3.30), and social deprivation (HR 1.53; 1.11-2.11) increased risk of progression to the composite end point. CONCLUSION: The risk of incident MI, angina, and revascularization is increased in young women with PCOS. Weight and T2DM are potentially modifiable risk factors amenable to intervention.

Long-term cardiometabolic disease risk in women with PCOS: a systematic review and meta-analysis.

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.

Association between polycystic ovary syndrome and the risk of stroke and all-cause mortality: insights from a meta-analysis.

Many epidemiologic literatures have investigated the link between PCOS and long-term stroke risk and all-cause mortality, but the results are surprisingly conflicting. A meta-analysis was performed to examine the link between polycystic ovary syndrome (PCOS) and the risk of stroke, death from any cause, and assessed whether BMI might explain a higher risk of stroke. We searched the PUBMED, EMBASE, and Cochrane Library databases with no restrictions. Nine Cohort studies were identified, involving a total of 237,647 subjects. Compared with those without PCOS, subjects with PCOS were significantly associated with a increased risk of developing stroke (OR = 1.36; 95% CI 1.09-1.70; p = .007). However, no significant association was observed between PCOS and all-cause death (OR = 1.21; 95% CI 0.88-1.66; p = .25). Moreover, after pooling the five studies with risk estimates adjusted for BMI, the association between PCOS and stroke was slightly attenuated, although the odds ratios did not reach statistical significance (OR = 1.24; 95% CI 0.98-1.59). In conclusion, PCOS is associated with significant increased risk for stroke, while there is no consistent evidence to indicate that PCOS influences all-cause death outcomes. Increased BMI is an important contributor to the relationship between PCOS and stroke risk. Further study is needed to clarify which subgroups of subjects with the PCOS are at higher risk for stroke and should focus on developing reliable device for risk stratification.

Phosphatidylinositide-3 kinase: a newer molecular target in metabolic and hormonal pathway of polycystic ovary syndrome.

Polycystic ovary syndrome is characterized by hyperandrogenemia, hyperinsulinemia and/or abnormal ovulation, which are the 3 main consequences of polycystic ovary syndrome. The occurrence of polycystic ovary syndrome is higher and 1 out of 45 women gets affected by this disorder. The pathophysiology of polycystic ovary syndrome is very unique, and many hormonal and metabolic changes occur at molecular level. Polycystic ovary syndrome is a hormonal disorder that affects multiple organ systems within the body, which is caused by insensitivity to the hormone insulin. The target organs of insulin action are skeletal muscles, adipose tissue, fibroblasts where metabolic actions of insulin take place. In polycystic ovary syndrome condition, due to insulin resistance, the actions like glucose uptake and glycogen synthesis gets declined along with exhibiting steroidogenic effect in ovaries. The action of phophatidylinositide-3 kinase varies in different tissues. It plays major role in several kinases. The inhibition and activation of phophatidylinositide-3 kinase in different tissues results in differential outcomes. The inhibition of phophatidylinositide-3 kinase in ovary leads to decreased androgen synthesis and the activation affects the positive actions of insulin like glucose uptake. Targeting the hyperandrogenemia of polycystic ovary syndrome, we can get more ameliorating action in polycystic ovary syndrome because glucose uptake, which is mediated by phophatidylinositide-3 kinase activation, is not much altered during polycystic ovary syndrome as much as the androgen levels in polycystic ovary syndrome. Therefore, it is beneficial to control the androgen level. Thus, phophatidylinositide-3 kinase inhibition can be a promising target in the treatment of polycystic ovary syndrome.

Evaluation of adverse outcome in young women with polycystic ovary syndrome versus matched, reference controls: a retrospective, observational study.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with insulin resistance, hyperandrogenism, and dyslipidemia, but the effects of these disturbances on long-term health are not fully understood. AIM: Our aim was to determine the relative risk of type 2 diabetes, cancer, large-vessel disease (LVD), and all-cause mortality for women diagnosed with PCOS. DESIGN: Data were extracted from the General Practice Research Database, a longitudinal, anonymized research database derived from nearly 600 primary-care practices in the United Kingdom. Patients with a diagnosis of PCOS between 1990 and 2010 were selected. Patients were matched to two sets of controls. The first set was matched according to primary-care practice and age, and the second was also matched on body mass index. Primary outcome was first incident record of diabetes. Crude rates for diabetes were presented, and time to diabetes was analyzed using Cox proportional hazard models. Secondary outcomes (cancer, LVD, and mortality) were also modeled. RESULTS: Of 53,303 identified with a diagnosis of PCOS, 21,740 (40.8%) met the eligibility criteria. Median follow-up was 4.7 yr (interquartile range = 2.0-8.6 yr) in those with PCOS and 5.8 yr (2.7-9.6) in the reference group. Crude rates of diabetes were 5.7 and 1.7 per 1000 patient-years for cases and controls, respectively. The corresponding adjusted hazard ratio was 3.015 (95% confidence interval = 2.733-3.327). Of cases matched by body mass index, crude rates of diabetes were 4.7 and 2.4 per 1000 patient-years, respectively. The corresponding adjusted hazard ratio was 1.752 (1.514-2.028). No significant difference in BMI-adjusted risk was evident for cancer, LVD, or all-cause mortality. CONCLUSIONS: During this follow-up period, women with PCOS were not at increased risk of LVD, cancer, or death, but they had increased risk of type 2 diabetes.

Risk of T2DM and impaired fasting glucose among PCOS subjects: results of an 8-year follow-up.

Women with polycystic ovary syndrome (PCOS) often develop type 2 diabetes mellitus (T2DM). To determine the magnitude of risk of developing T2DM among women with PCOS, development of T2DM was prospectively assessed among women who had T2DM (n = 97) and controls (n = 95) using Kaplan-Meier survival analysis and Cox proportional hazards modeling. The women with T2DM had higher baseline weight (body mass index, P < 0.01) and lower insulin sensitivity (homeostasis assessment model of insulin resistance, P < 0.01). The 8-year incidence rate among cases and controls was 13.4% and 5.8%, respectively (relative risk = 2.3). Obese cases had a fivefold risk of T2DM developing (P < 0.01) compared with age-adjusted obese controls, indicating significant interaction between PCOS and obesity to effect T2DM risk.

Is plasminogen activator inhibitor-1 a cardiovascular risk factor in young women with polycystic ovary syndrome?

This study aimed to evaluate plasminogen activator inhibitor-1 (PAI-1) activity in PCOS. Thirty women with PCOS - 15 normal-weight and 15 obese - and 30 healthy women matched as a group for age and body mass index (BMI) were recruited. The homeostasis model assessment (HOMA) score was significantly elevated in obese compared with normal-weight women, in both PCOS women and controls. HOMA score was significantly higher in both PCOS groups relative to controls. After further adjustment for BMI, PAI-1 activity (IU/ml +/- SD) was significantly higher in the PCOS groups compared with controls. A significant positive correlation was found between HOMA score and BMI in PCOS and control groups. Serum PAI-1 activity was significantly related to BMI and HOMA score. When considering two BMI subgroups, there was no significant difference in the relationship between serum PAI-1 activity and HOMA score in both the control and PCOS groups. No other significant relationship was found between serum PAI-1 activity and any other hormonal or metabolic parameter. In conclusion, women with PCOS have significantly elevated PAI-1 activity independent of obesity, and it is speculated that elevated PAI-1 activity may be a factor in the increased cardiovascular morbidity seen in PCOS.

Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with higher prevalence of cardiovascular risk factors but the relative prevalence of cardiovascular disease in women with PCOS has not previously been reported. We have compared cardiovascular mortality and morbidity in middle-aged women previously diagnosed with PCOS and age-matched control women. DESIGN: A retrospective cohort study of women diagnosed with PCOS in the United Kingdom before 1979. PATIENTS: Seventy cohort members died before 31 March 1999. Morbidity data were collected from 319 women with PCOS and 1060 age-matched control women. Sixty-one women with PCOS and 63 control women attended a clinical examination. MEASUREMENTS: Data were collected from death certificates, general practitioners' records and questionnaires with measurement of cardiovascular risk factors in a subsample of questionnaire respondents. RESULTS: All-cause and cardiovascular mortality in the cohort were similar to women in the general population (standardized mortality ratios (95% CI): 93 (72-117) and 78 (45-124), respectively). Women with PCOS had higher levels of several cardiovascular risk factors: diabetes (P = 0.002) hypertension (P = 0.04), hypercholesterolaemia (P < 0.001), hypertriglyceridaemia (P = 0.02) and increased waist:hip ratio (P = 0.004). After adjustment for BMI, odds ratios (OR) were 2.2 (0.9-5. 2) for diabetes, 1.4 (0.9-2.0) for hypertension and 3.2 (1.7-6.0) for hypercholesterolaemia. A history of coronary heart disease (CHD) was not significantly more common in women with PCOS (crude OR (95%CI) 1.5 (0.7-2.9)) but the crude OR for cerebrovascular disease was 2.8 (1.1-7.1). CONCLUSION: At long-term follow-up, a history of nonfatal cerebrovascular disease and cardiovascular risk factors including diabetes are more prevalent among women with polycystic ovary syndrome. Morbidity and mortality from of coronary heart disease among women with polycystic ovary syndrome is not as high as previously predicted. This finding challenges our understanding of the aetiology of coronary heart disease in women.