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Associations Between Measures of Sarcopenic Obesity and Risk of Cardiovascular Disease and Mortality: A Cohort Study and Mendelian Randomization Analysis Using the UK Biobank

Farmer, RE; Mathur, R; Schmidt, AF; Bhaskaran, K; Fatemifar, G; Eastwood, SV; Finan, C; ... Chaturvedi, N; + view all (2019) Associations Between Measures of Sarcopenic Obesity and Risk of Cardiovascular Disease and Mortality: A Cohort Study and Mendelian Randomization Analysis Using the UK Biobank. Journal of the American Heart Association , 8 (13) , Article e011638. 10.1161/JAHA.118.011638. Green open access

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Abstract

Background The "healthy obese" hypothesis suggests the risks associated with excess adiposity are reduced in those with higher muscle quality (mass/strength). Alternative possibilities include loss of muscle quality as people become unwell (reverse causality) or unmeasured confounding. Methods and Results We conducted a cohort study using the UK Biobank (n=452 931). Baseline body mass index ( BMI) was used to quantify adiposity and handgrip strength ( HGS ) used for muscle quality. Outcomes were fatal and non-fatal cardiovascular disease, and mortality. As a secondary analysis we used waist-hip-ratio or fat mass percentage instead of BMI , and skeletal muscle mass index instead of HGS . In a subsample, we used gene scores for BMI , waist-hip-ratio and HGS in a Mendelian randomization ( MR ). BMI defined obesity was associated with an increased risk of all outcomes (hazard ratio [ HR ] range 1.10-1.82). Low HGS was associated with increased risks of cardiovascular and all-cause mortality ( HR range 1.39-1.72). HR s for the association between low HGS and cardiovascular disease events were smaller ( HR range 1.05-1.09). There was no suggestion of an interaction between HGS and BMI to support the healthy obese hypothesis. Results using other adiposity metrics were similar. There was no evidence of an association between skeletal muscle mass index and any outcome. Factorial Mendelian randomization confirmed no evidence for an interaction. Low genetically predicted HGS was associated with an increased risk of mortality ( HR range 1.08-1.19). Conclusions Our analyses do not support the healthy obese concept, with no evidence that the adverse effect of obesity on outcomes was reduced by improved muscle quality. Lower HGS was associated with increased risks of mortality in both observational and MR analyses, suggesting reverse causality may not be the sole explanation.

Type: Article
Title: Associations Between Measures of Sarcopenic Obesity and Risk of Cardiovascular Disease and Mortality: A Cohort Study and Mendelian Randomization Analysis Using the UK Biobank
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/JAHA.118.011638
Publisher version: https://doi.org/10.1161/JAHA.118.011638
Language: English
Additional information: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/
Keywords: Mendelian randomization, cardiovascular outcomes, epidemiology, grip strength, obesity
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology
URI: https://discovery.ucl.ac.uk/id/eprint/10077092
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