PMID- 33592239
OWN - NLM
STAT- MEDLINE
DCOM- 20210528
LR  - 20240210
IS  - 1874-1754 (Electronic)
IS  - 0167-5273 (Linking)
VI  - 330
DP  - 2021 May 1
TI  - Estimating the causal effect of BMI on mortality risk in people with heart 
      disease, diabetes and cancer using Mendelian randomization.
PG  - 214-220
LID - S0167-5273(21)00280-1 [pii]
LID - 10.1016/j.ijcard.2021.02.027 [doi]
AB  - BACKGROUND: Observational data have reported that being overweight or obese, 
      compared to being normal weight, is associated with a lower risk for death - the 
      "obesity paradox". We used Mendelian randomization (MR) to estimate causal 
      effects of body mass index (BMI) on mortality risks in people with coronary heart 
      disease (CHD), type 2 diabetes mellitus (T2DM) or malignancy in whom this paradox 
      has been often reported. METHODS: We studied 457,746 White British UK Biobank 
      participants including three subgroups with T2DM (n = 19,737), CHD (n = 21,925) 
      or cancer (n = 42,612) at baseline and used multivariable-adjusted Cox models and 
      MR approaches to describe relationships between BMI and mortality risk. RESULTS: 
      Observational Cox models showed J-shaped relationships between BMI and mortality 
      risk including within disease subgroups in which the BMI values associated with 
      minimum mortality risk were within overweight/obese ranges (26.5-32.5 kg/m(2)). 
      In all participants, MR analyses showed a positive linear causal effect of BMI on 
      mortality risk (HR for mortality per unit higher BMI: 1.05; 95% CI: 1.03-1.08), 
      also evident in people with CHD (HR: 1.08; 95% CI: 1.01-1.14). Point estimates 
      for hazard ratios across all BMI values in participants with T2DM and cancer were 
      consistent with overall positive linear effects but confidence intervals included 
      the null. CONCLUSION: These data support the idea that population efforts to 
      promote intentional weight loss towards the normal BMI range would reduce, not 
      enhance, mortality risk in the general population including, importantly, 
      individuals with CHD.
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Jenkins, David A
AU  - Jenkins DA
AD  - NIHR Greater Manchester Patient Safety Translational Research Centre, The 
      University of Manchester, Manchester, UK; School of Health Sciences, Faculty of 
      Biology, Medicine and Health, The University of Manchester, Oxford Road, 
      Manchester M13 9PL, UK. Electronic address: david.jenkins-5@manchester.ac.uk.
FAU - Wade, Kaitlin H
AU  - Wade KH
AD  - MRC Integrative Epidemiology Unit, Population Health Sciences, Oakfield House, 
      Oakfield Grove, University of Bristol, Bristol BS8 2BN, UK.
FAU - Carslake, David
AU  - Carslake D
AD  - MRC Integrative Epidemiology Unit, Population Health Sciences, Oakfield House, 
      Oakfield Grove, University of Bristol, Bristol BS8 2BN, UK.
FAU - Bowden, Jack
AU  - Bowden J
AD  - MRC Integrative Epidemiology Unit, Population Health Sciences, Oakfield House, 
      Oakfield Grove, University of Bristol, Bristol BS8 2BN, UK; Exeter Diabetes Group 
      (ExCEED), College of Medicine and Health, University of Exeter, Exeter, UK.
FAU - Sattar, Naveed
AU  - Sattar N
AD  - Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, 
      UK.
FAU - Loos, Ruth J F
AU  - Loos RJF
AD  - The Charles Bronfman Institute for Personalized Medicine, Icahn School of 
      Medicine at Mount Sinai, New York, NY 10029, USA; The Mindich Child Health 
      Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029, USA.
FAU - Timpson, Nicholas J
AU  - Timpson NJ
AD  - MRC Integrative Epidemiology Unit, Population Health Sciences, Oakfield House, 
      Oakfield Grove, University of Bristol, Bristol BS8 2BN, UK.
FAU - Sperrin, Matthew
AU  - Sperrin M
AD  - School of Health Sciences, Faculty of Biology, Medicine and Health, The 
      University of Manchester, Oxford Road, Manchester M13 9PL, UK.
FAU - Rutter, Martin K
AU  - Rutter MK
AD  - Division of Endocrinology, Diabetes & Gastroenterology, School of Medical 
      Sciences, Faculty of Biology, Medicine and Health, University of Manchester, 
      Oxford Rd, Manchester M13 9PL, UK; Diabetes, Endocrinology and Metabolism Centre, 
      Peter Mount Building, Manchester Royal Infirmary, Manchester University NHS 
      Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 0HY, 
      UK.
LA  - eng
GR  - MR/K006665/1/MRC_/Medical Research Council/United Kingdom
GR  - 29019/CRUK_/Cancer Research UK/United Kingdom
GR  - MC_UU_00011/2/MRC_/Medical Research Council/United Kingdom
GR  - 19169/CRUK_/Cancer Research UK/United Kingdom
GR  - 202802/Z/16/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
DEP - 20210214
PL  - Netherlands
TA  - Int J Cardiol
JT  - International journal of cardiology
JID - 8200291
SB  - IM
MH  - Body Mass Index
MH  - *Diabetes Mellitus, Type 2/diagnosis
MH  - Humans
MH  - Mendelian Randomization Analysis
MH  - *Neoplasms/diagnosis
MH  - Obesity/diagnosis
MH  - Risk Factors
OTO - NOTNLM
OT  - Coronary heart disease
OT  - Mortality
OT  - Obesity
COIS- Declaration of Competing Interest MKR reports speaker fees from Novo Nordisk and 
      modest stock ownership in GSK. NS has consulted for Astrazeneca, Boehringer 
      Ingelheim, Eli-Lilly, Napp, Novo Nordisk, Pfizer and Sanofi. The remaining 
      authors have nothing to disclose.
EDAT- 2021/02/17 06:00
MHDA- 2021/05/29 06:00
CRDT- 2021/02/16 20:09
PHST- 2020/08/12 00:00 [received]
PHST- 2021/02/02 00:00 [revised]
PHST- 2021/02/11 00:00 [accepted]
PHST- 2021/02/17 06:00 [pubmed]
PHST- 2021/05/29 06:00 [medline]
PHST- 2021/02/16 20:09 [entrez]
AID - S0167-5273(21)00280-1 [pii]
AID - 10.1016/j.ijcard.2021.02.027 [doi]
PST - ppublish
SO  - Int J Cardiol. 2021 May 1;330:214-220. doi: 10.1016/j.ijcard.2021.02.027. Epub 
      2021 Feb 14.