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Do worse baseline risk factors explain the association of healthy obesity with increased mortality risk? Whitehall II Study

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journal contribution
posted on 08.07.2019, 14:42 by William Johnson, Joshua A. Bell, Ellie Robson, Tom Norris, Mika Kivimäki, Mark Hamer
Objective To describe 20-year risk factor trajectories according to initial weight/health status and investigate the extent to which baseline differences explain greater mortality among metabolically healthy obese (MHO) individuals than healthy non-obese individuals. Methods The sample comprised 6529 participants in the Whitehall II study who were measured serially between 1991–1994 and 2012–2013. Baseline weight (non-obese or obese; body mass index (BMI) ≥30 kg/m2) and health status (healthy or unhealthy; two or more of hypertension, low high-density lipoprotein cholesterol (HDL-C), high triglycerides, high glucose, and high homeostatic model assessment of insulin resistance (HOMA-IR)) were defined. The relationships of baseline weight/health status with 20-year trajectories summarizing ~25,000 observations of systolic and diastolic blood pressures, HDL-C, triglycerides, glucose, and HOMA-IR were investigated using multilevel models. Relationships of baseline weight/health status with all-cause mortality up until July 2015 were investigated using Cox proportional hazards regression. Results Trajectories tended to be consistently worse for the MHO group compared to the healthy non-obese group (e.g., glucose by 0.21 (95% CI 0.09, 0.33; p < 0.001) mmol/L at 20-years of follow-up). Consequently, the MHO group had a greater risk of mortality (hazard ratio 2.11 (1.24, 3.58; p = 0.006)) when the referent group comprised a random sample of healthy non-obese individuals. This estimate, however, attenuated (1.34 (0.85, 2.13; p = 0.209)) when the referent group was matched to the MHO group on baseline risk factors. Conclusions Worse baseline risk factors may explain any difference in mortality risk between obese and non-obese groups both labelled as healthy, further challenging the concept of MHO.


This work was supported by the UK Medical Research Council (WJ New Investigator Research Grant: MR/P023347/1). W.J. and M.H. acknowledge support from the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, which is a partnership between University Hospitals of Leicester NHS Trust, Loughborough University, and the University of Leicester. J.A.B. is supported by a Cancer Research UK programme grant (C18281/A19169). The UK Medical Research Council (MR/K013351/1; G0902037), British Heart Foundation (RG/13/2/30098, PG/11/63/29011), and the US National Institutes of Health (R01HL36310, R01AG013196) have supported collection of data in the Whitehall II Study. M.K. was additionally supported by NordForsk and a Helsinki Institute of Life Science fellowship.



International Journal of Obesity, 2018

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International Journal of Obesity


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We thank all participants in the Whitehall II Study, Whitehall II researchers, and support staff who make the study possible. Please refer to the Whitehall II data sharing policy at http://www.ucl.ac.uk/whitehallII/data-sharing. Whitehall II data are available to bona fide researchers for research purposes



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