Creatinine Muscle Index in UK Biobank: Comparison with MRI and associations with Frailty and Mortality

Abstract Background Skeletal muscle wasting due to aging, acute illness and chronic disease is associated with adverse outcomes including mortality, frailty and multi-morbidity. We investigated the relationship of creatinine muscle index (CMI), a serum biological signature of muscle mass, in UK Biobank participants with gold standard muscle measurement and adverse outcomes. Method We compared CMI with Magnetic Resonance Imaging (MRI) measured muscle mass in 33 799 participants using linear regression. We then assessed CMI’s ability to discriminate low muscle mass (≤2.5 SD below the mean). In the full UK Biobank cohort (n = 450 812), we utilised Cox-proportional hazards models to investigate associations between CMI with mortality, frailty and comorbidity. Results CMI demonstrated moderate to good linear correlation with gold-standard MRI muscle mass measurements (R males: 0.68 [0.60–0.76]; females: 0.65 [0.56–0.73]), after accounting for data imbalance. CMI discriminated muscle mass ≤ 2.5 standard deviations from the mean, with an area under the curve of 0.80 (95% CI:0.75–0.86) in males and 0.84 (95% CI:0.78–0.89) in females. CMI consistently decreased with increasing age, frailty and comorbidity. Over an 8-year follow-up, lower CMI was associated with higher morality: adjusted hazard ratio for the 25th vs 75th CMI centiles were 0.61(95% CI: 0.58–0.66) in males and 0.72 (95% CI: 0.66–0.78) in females. Conclusions In over 450 000 UK Biobank participants, low CMI was significantly associated with baseline comorbidity, frailty and survival on follow-up (independent of age, sex and comorbidity). This study supports CMI as a potential biological signature for skeletal muscle wasting in clinical and research settings.