Sarcopenia, Obesity, and Mortality in US Adults With and Without Chronic Kidney Disease

In predialysis chronic kidney disease (CKD), the association of muscle mass with mortality is poorly defined, and no study has examined outcomes related to the co-occurrence of low muscle mass and excess adiposity (sarcopenic obesity). Methods: We examined abnormalities of muscle and fat mass in adult participants of the National Health and Nutrition Examination Survey 1999–2004. We determined whether associations of body composition with all-cause mortality differed between participants with CKD compared to those without. Results: CKD modified the association of body composition with mortality (P = 0.01 for interaction). In participants without CKD, both sarcopenia and sarcopenic obesity were independently associated with increased mortality compared with normal body composition (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.07–1.93, and HR = 1.64, 95% CI = 1.26–2.13, respectively). These associations were not present among participants with CKD. Conversely, obese persons had the lowest adjusted risk of death, with an increased risk among those with sarcopenia (HR = 1.43, 95% CI = 1.05–1.95) but not sarcopenic-obesity (P = 0.003 for interaction by CKD status; HR = 1.21, 95% CI = 0.89–1.65), compared with obesity. Discussion: Sarcopenia associates with increased mortality regardless of estimated glomerular filtration rate, but excess adiposity modifies this association among persons with CKD. Future studies of prognosis and weight loss and exercise interventions in CKD patients should consider muscle mass and adiposity together rather than in isolation

Correction: Muscle mass, BMI, and mortality among adults in the United States: A population-based cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0194697.]

Muscle mass, BMI, and mortality among adults in the United States: A population-based cohort study

<div><p>Background</p><p>The level of body-mass index (BMI) associated with the lowest risk of death remains unclear. Although differences in muscle mass limit the utility of BMI as a measure of adiposity, no study has directly examined the effect of muscle mass on the BMI-mortality relationship.</p><p>Methods</p><p>Body composition was measured by dual-energy x-ray absorptiometry in 11,687 participants of the National Health and Nutrition Examination Survey 1999–2004. Low muscle mass was defined using sex-specific thresholds of the appendicular skeletal muscle mass index (ASMI). Proportional hazards models were created to model associations with all-cause mortality.</p><p>Results</p><p>At any level of BMI ≥22, participants with low muscle mass had higher body fat percentage (%TBF), an increased likelihood of diabetes, and higher adjusted mortality than other participants. Increases in %TBF manifested as 30–40% smaller changes in BMI than were observed in participants with preserved muscle mass. Excluding participants with low muscle mass or adjustment for ASMI attenuated the risk associated with low BMI, magnified the risk associated with high BMI, and shifted downward the level of BMI associated with the lowest risk of death. Higher ASMI was independently associated with lower mortality. Effects were similar in never-smokers and ever-smokers. Additional adjustment for waist circumference eliminated the risk associated with higher BMI. Results were unchanged after excluding unintentional weight loss, chronic illness, early mortality, and participants performing muscle-strengthening exercises or recommended levels of physical activity.</p><p>Conclusions</p><p>Muscle mass mediates associations of BMI with adiposity and mortality and is inversely associated with the risk of death. After accounting for muscle mass, the BMI associated with the greatest survival shifts downward toward the normal range. These results provide a concrete explanation for the obesity paradox.</p></div

Association of BMI with all-cause mortality without and with adjustment for appendicular skeletal muscle mass index and waist circumference.

<p>Models adjusted for age, sex, race/ethnicity, smoking status, physical activity level, and education. Error bars represent 95% confidence intervals.</p

The risk of death according to BMI for the full cohort (upper panel) and for participants with preserved muscle mass (lower panel).

<p>Mortality modeled as a restricted cubic spline and models adjusted for age, sex, race/ethnicity, smoking status, physical activity level, and education. The shaded area represents the 95% confidence interval.</p

Association of BMI with all-cause mortality without and with adjustment for appendicular skeletal muscle mass index for the full cohort.

<p>Models adjusted for age, sex, race/ethnicity, smoking status, physical activity level, and education. Error bars represent 95% confidence intervals.</p

Participant characteristics by muscle mass status and BMI in 11,687 participants of NHANES 1999–2004.

<p>Participant characteristics by muscle mass status and BMI in 11,687 participants of NHANES 1999–2004.</p

Association of BMI with all-cause mortality without and with adjustment for appendicular skeletal muscle mass index after stratification by smoking status.

<p>Models adjusted for age, sex, race/ethnicity, smoking status, physical activity level, and education. Error bars represent 95% confidence intervals.</p

Risk of all-cause mortality by BMI category and muscle mass status.

<p>Bars indicate prevalence of low muscle mass in each BMI category. One participant with BMI >35 (38 kg/m²) had low muscle mass and was grouped with participants with BMI 30-<35 kg/m² for statistical analysis. Models adjusted for age, sex, race/ethnicity, smoking status, physical activity level, and education. Error bars represent 95% confidence intervals.</p