Associations between body mass index, biological age and frailty in the critically ill

The relationship between body mass index (BMI) and outcomes in the acute care setting is controversial, with evidence suggesting that obesity is either protective - which is also called obesity paradox - or associated with worse outcomes. The purpose of this study was to assess whether BMI was related to frailty and biological age, and whether BMI remained predictive of mortality after adjusting for frailty and biological age.

Of the 2950 patients who had a biological age estimated on admission to the intensive care unit, 877 (30 %) also had BMI and frailty data available for further analysis in this retrospective cohort study.

Biological age of each patient was estimated using the Levine PhenoAge model based on results of nine blood tests that were reflective of DNA methylation. Biological age in excess of chronological age was then indexed to the local study context by a linear regression to generate the residuals. The associations between BMI, clinical frailty scale, and the residuals were first analyzed using univariable analyses. Their associations with mortality were then assessed by multivariable analysis, including the use of a 3-knot restricted cubic spline function to allow non-linearity.

Both frailty (p = 0.003) and the residuals of the biological age (p = 0.001) were related to BMI in a U-shaped fashion. BMI was not related to hospital mortality, but both frailty (p = 0.015) and the residuals of biological age (OR per decade older than chronological age 1.50, 95 % confidence interval [CI] 1.04-2.18; p = 0.031) were predictive of mortality after adjusting for chronological age, diabetes mellitus and severity of acute illness.

BMI was significantly associated with both frailty and biological age in a U-shaped fashion but only the latter two were related to mortality. These results may, in part, explain why obesity paradox could be observed in some studies.