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

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.

Fig 1

Association of predicted body composition and body mass index (BMI)* with all cause mortality in men. A: Fat mass and all cause mortality. B: Lean body mass and all cause mortality. C: BMI and all cause mortality. Hazard ratios are indicated by solid lines and 95% CIs by shaded areas. Reference point is lowest value for each of fat mass and lean body mass and 25 for BMI, with knots placed at 5th, 35th, 50th, 65th, and 95th centiles of each fat mass, lean body mass, and BMI distribution. All models were adjusted for cofounders in table 2. For graphs A and B, predicted fat mass and predicted lean body mass were mutually adjusted. *Standard deviations: 5.7 kg for fat mass, 6.6 kg for lean body mass, and 3.1 for BMI; centiles (0, 2.5, 5, 10, 25, 50, 75, 90, and 100): 7, 13, 14, 15, 18, 21, 25, 29, and 66 kg for fat mass; 24, 48, 49, 51, 53, 56, 59, 63, and 103 kg for lean body mass; and 14.2, 20.5, 21.2, 22.0, 23.4, 25.1, 27.0, 29.3, and 62.0 for BMI