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Predicted lean body mass, fat mass, and all cause and cause specific mortality in men: prospective US cohort study

BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k2575 (Published 03 July 2018) Cite this as: BMJ 2018;362:k2575
  1. Dong Hoon Lee, post-doctoral research fellow1,
  2. NaNa Keum, visiting scientist, assistant professor12,
  3. Frank B Hu, professor1 3 4,
  4. E John Orav, associate professor4 5,
  5. Eric B Rimm, professor1 3 4,
  6. Walter C Willett, professor1 3 4,
  7. Edward L Giovannucci, professor1 3 4
  1. 1Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
  2. 2Department of Food Science and Biotechnology, Dongguk University, Goyang, South Korea
  3. 3Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
  4. 4Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
  5. 5Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
  1. Correspondence to: E L Giovannucci egiovann{at}hsph.harvard.edu
  • Accepted 23 May 2018

Abstract

Objective To investigate the association of predicted lean body mass, fat mass, and body mass index (BMI) with all cause and cause specific mortality in men.

Design Prospective cohort study.

Setting Health professionals in the United States

Participants 38 006 men (aged 40-75 years) from the Health Professionals Follow-up Study, followed up for death (1987-2012).

Main outcome measures All cause and cause specific mortality.

Results Using validated anthropometric prediction equations previously developed from the National Health and Nutrition Examination Survey, lean body mass and fat mass were estimated for all participants. During a mean of 21.4 years of follow-up, 12 356 deaths were identified. A J shaped association was consistently observed between BMI and all cause mortality. Multivariable adjusted Cox models including predicted fat mass and lean body mass showed a strong positive monotonic association between predicted fat mass and all cause mortality. Compared with those in the lowest fifth of predicted fat mass, men in the highest fifth had a hazard ratio of 1.35 (95% confidence interval 1.26 to 1.46) for mortality from all causes. In contrast, a U shaped association was found between predicted lean body mass and all cause mortality. Compared with those in the lowest fifth of predicted lean body mass, men in the second to fourth fifths had 8-10% lower risk of mortality from all causes. In the restricted cubic spline models, the risk of all cause mortality was relatively flat until 21 kg of predicted fat mass and increased rapidly afterwards, with a hazard ratio of 1.22 (1.18 to 1.26) per standard deviation. For predicted lean body mass, a large reduction of the risk was seen within the lower range until 56 kg, with a hazard ratio of 0.87 (0.82 to 0.92) per standard deviation, which increased thereafter (P for non-linearity <0.001). For cause specific mortality, men in the highest fifth of predicted fat mass had hazard ratios of 1.67 (1.47 to 1.89) for cardiovascular disease, 1.24 (1.09 to 1.43) for cancer, and 1.26 (0.97 to 1.64) for respiratory disease. On the other hand, a U shaped association was found between predicted lean body mass and mortality from cardiovascular disease and cancer. However, a strong inverse association existed between predicted lean body mass and mortality from respiratory disease (P for trend <0.001).

Conclusions The shape of the association between BMI and mortality was determined by the relation between two body components (lean body mass and fat mass) and mortality. This finding suggests that the “obesity paradox” controversy may be largely explained by low lean body mass, rather than low fat mass, in the lower range of BMI.

Footnotes

  • Contributors: DHL and ELG had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. DHL and ELG conceived and designed the study. NK, FBH, EBR, WCW, and ELG obtained funding. FBH, EJO, EBR, WCW, and ELG acquired the data. DHL did the statistical analysis. DHL and ELG drafted the manuscript. All the authors critically revised the manuscript for important intellectual content. DHL and ELG were responsible for administrative, technical, or material support. ELG was responsible for study supervision. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. DHL is the guarantor.

  • Funding: This work was supported by the National Institutes of Health (UM1 CA167552, R01 HL35464, and R03 CA223619) and the Basic Research Lab Program through the National Research Foundation of Korea (NRF) funded by the MSIT (NRF-2018R1A4A1022589). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organization for the submitted work other than that described above; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This investigation was approved by the Institutional Review Board of the Harvard T.H. Chan School of Public Health and Brigham and Women’s Hospital.

  • Transparency declaration: The lead author (the manuscript's guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Data sharing: No additional data available.

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