The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC

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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SummaryBackgroundPersistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling.MethodsIn a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6.FindingsThe minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0·04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34·3% (95% CI 30·4–38·2) and of interleukin 6 by 14·6% (10·7–18·4), and mean concentration of C-reactive protein was reduced by 7·5% (5·9–9·1) and of fibrinogen by 1·0% (0·7–1·3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3·4% (1·8–5·0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes.InterpretationLarge-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.FundingBritish Heart Foundation; UK Medical Research Council; UK National Institute of Health Research, Cambridge Biomedical Research Centre; BUPA Foundation.

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This is the first reported validation study of an international standardized questionnaire (IPAQ-C) in older Chinese adults. Our study shows that the IPAQ-C is adequately valid and reliable for assessing total physical activity and that it may be a useful instrument for generating internationally comparable data on physical activity in this population.

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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.