Krishnarajah. (2017) Metabolically healthy obese and incident cardiovascular disease events among 3.5 million men and women. Journal of the American College of Cardiology, 70 (12). pp. 1429-1437. Permanent WRAP URL:http://wrap.warwick.ac.uk/94321 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-for-profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. A note on versions:The version presented here may differ from the published version or, version of record, if you wish to cite this item you are advised to consult the publisher's version. Please see the 'permanent WRAP url' above for details on accessing the published version and note that access may require a subscription. (1995 to 2015) in The Health Improvement Network (THIN) to assemble a cohort of 3.5 million individuals, 18 years or older and initially free from cardiovascular disease. We created body size phenotypes defined by BMI categories (underweight, normal weight, overweight and obesity) and three metabolic abnormalities (diabetes, hypertension, and hyperlipidemia). The primary endpoints were the first record of one of 4 cardiovascular presentations [coronary heart disease (CHD), cerebrovascular disease, heart failure, and peripheral vascular disease (PVD)].Results: During a mean follow-up period of 5.4 years, obese individuals with 0 metabolic abnormalities had a higher risk of CHD (multivariable-adjusted hazard ratio (HR) 1.49, 95% CI 1.45, 1.54), cerebrovascular disease (1.07, 95% CI 1.04, 1.11) and heart failure (1.96, 95% CI 1.86, 2.06) compared to normal weight individuals with 0 metabolic abnormalities. Risk of CHD, cerebrovascular disease and heart failure in normal weight, overweight and obese individuals increased with increasing number of metabolic abnormalities. Conclusion: Metabolically healthy obese individuals had a higher risk of coronary heart disease, cerebrovascular disease and heart failure than normal weight metabolically healthy individuals. Even individuals who are normal weight can have metabolic abnormalities, and have similar risks for cardiovascular disease events.

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BackgroundGestational diabetes mellitus (GDM) is associated with developing type 2 diabetes, but very few studies have examined its effect on developing cardiovascular disease.Methods and findingsWe conducted a retrospective cohort study utilizing a large primary care database in the United Kingdom. From 1 February 1990 to 15 May 2016, 9,118 women diagnosed with GDM were identified and randomly matched with 37,281 control women by age and timing of pregnancy (up to 3 months). Adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated for cardiovascular risk factors and cardiovascular disease. Women with GDM were more likely to develop type 2 diabetes (IRR = 21.96; 95% CI 18.31–26.34) and hypertension (IRR = 1.85; 95% CI 1.59–2.16) after adjusting for age, Townsend (deprivation) quintile, body mass index, and smoking. For ischemic heart disease (IHD), the IRR was 2.78 (95% CI 1.37–5.66), and for cerebrovascular disease 0.95 (95% CI 0.51–1.77; p-value = 0.87), after adjusting for the above covariates and lipid-lowering medication and hypertension at baseline. Follow-up screening for type 2 diabetes and cardiovascular risk factors was poor. Limitations include potential selective documentation of severe GDM for women in primary care, higher surveillance for outcomes in women diagnosed with GDM than control women, and a short median follow-up postpartum period, with a small number of outcomes for IHD and cerebrovascular disease.ConclusionsWomen diagnosed with GDM were at very high risk of developing type 2 diabetes and had a significantly increased incidence of hypertension and IHD. Identifying this group of women in general practice and targeting cardiovascular risk factors could improve long-term outcomes.

After controlling for BMI-related effects, adiponectin levels seem to be lower in women with PCOS compared with non-PCOS controls. Low levels of adiponectin in PCOS are probably related to IR but not to testosterone. Total adiponectin should not be used as a biomarker of PCOS severity. Further investigation is needed for HMW adiponectin levels in PCOS.

A systematic search was conducted electronically using specific eligibility criteria. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated and combined appropriately. To ensure synthesis of the best available evidence, sensitivity analyses were performed. RESULTS A total of 130 data sets were included in 11 different outcomes, involving 7174 and 5076 CVD markers in women with PCOS and controls, respectively. Women with PCOS demonstrated significantly elevated CRP [WMD (95% CI) 0.99 (0.77-1.21)], Hcy [2.25 (1.46-3.03)], PAI-1 antigen [16.96 (7.25-26.28)], PAI-1 activity [0.71 (0.18-1.23)], VEGF [1.72 (0.96-2.48)], ADMA [0.19 (0.08-0.3)], AGEs [3.91 (2.36-5.45)] and Lp(a) [0.81 (0.58-1.04)] concentrations compared with controls, yet with significant between-study heterogeneity. Borderline significance (not robust in the sensitivity analyses) was detected for TNF-α [0.75 (0.07-1.44)], ET-1 [1.06 (0.52-1.59)] and fibrinogen [0.20 (0.01-0.39)], whereas no difference was detected for IL-6 [0.71 (-0.16 to 1.59)]. CONCLUSIONS Women with PCOS have increased serum concentrations of CVD risk markers compared with controls. Whether this apparent risk is translated into increased incidence of CVD in later life remains to be elucidated.

BackgroundAndrogen excess is a defining feature of polycystic ovary syndrome (PCOS), which affects 10% of women and represents a lifelong metabolic disorder, with increased risk of type 2 diabetes, hypertension, and cardiovascular events. Previous studies have suggested an increased risk of nonalcoholic fatty liver disease (NAFLD) in individuals with PCOS and implicated androgen excess as a potential driver.Methods and findingsWe carried out a retrospective longitudinal cohort study utilizing a large primary care database in the United Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, body mass index (BMI)-, and location-matched control women registered from January 2000 to May 2016. In 2 independent cohorts, we also determined the rate of NAFLD in women with a measurement of serum testosterone (n = 71,061) and sex hormone-binding globulin (SHBG; n = 49,625). We used multivariate Cox models to estimate the hazard ratio (HR) for NAFLD and found that women with PCOS had an increased rate of NAFLD (HR = 2.23, 95% CI 1.86–2.66, p < 0.001), also after adjusting for BMI or dysglycemia. Serum testosterone >3.0 nmol/L was associated with an increase in NAFLD (HR = 2.30, 95% CI 1.16–4.53, p = 0.017 for 3–3.49 nmol/L and HR = 2.40, 95% CI 1.24–4.66, p = 0.009 for >3.5 nmol/L). Mirroring this finding, SHBG <30 nmol/L was associated with increased NAFLD hazard (HR = 4.75, 95% CI 2.44–9.25, p < 0.001 for 20–29.99 nmol/L and HR = 4.98, 95% CI 2.45–10.11, p < 0.001 for <20 nmol/L). Limitations of this study include its retrospective nature, absence of detailed information on criteria used to diagnosis PCOS and NAFLD, and absence of data on laboratory assays used to measure serum androgens.ConclusionsWe found that women with PCOS have an increased rate of NAFLD. In addition to increased BMI and dysglycemia, androgen excess contributes to the development of NAFLD in women with PCOS. In women with PCOS-related androgen excess, systematic NAFLD screening should be considered.

On the basis of the best available evidence, Se supplementation is associated with a significant decrease in TPOab titers at 3 months and with improvement in mood and/or general well-being. Evidence suggests a different pattern of response to Se supplementation in HT relative to baseline TPOab titers, and this, if confirmed, could be used to identify which patients would benefit most from treatment. An improvement in thyroid function and morphology should be demonstrated before Se routine supplementation can be recommended in the treatment of HT.

Objective: To investigate whether thyroid autoimmunity (TAI) is associated with increased risk for spontaneous miscarriage in subfertile, euthyroid women undergoing IVF. Design: Meta-analysis of observational studies. Patient(s): Four prospective studies that reported data on 1098 subfertile women undergoing IVF (141 with TAI and 957 controls) were included in the meta-analysis. Main outcome measure: Miscarriage risk ratio (RR). Secondary outcome measures: Clinical pregnancy rate and delivery rate. Result(s): Euthyroid, subfertile women with TAI undergoing IVF demonstrated significantly higher risk for miscarriage compared with controls (four studies-fixed effects RR: 1.99, 95% confidence interval: 1.42-2.79, P!0.001). No significant difference in clinical pregnancy and delivery rates was detected between groups. Conclusion: Based on the currently available evidence, it appears that the presence of TAI is associated with an increased risk for spontaneous miscarriage in subfertile women achieving a pregnancy through an IVF procedure.