BackgroundFrailty is a hallmark of unhealthy ageing characterized by a decline in the general physiological state, strength and endurance of the patient and consequently, a greater vulnerability to endogenous and/or exogenous stressors. Behind this condition there are multiple pathophysiological processes affecting different systems, such as the musculoskeletal, reflected in sarcopenia, where anabolism is reduced in turn of catabolism. Underlying these processes, chronic inflammation is a well-known but not properly dissected mechanism that contributes to frailty. Although several studies suggest an association of TNF-α, IL-6, IL1-β with systemic inflammation in frail patients, the results are not conclusive. Some authors have explored other molecules related to inflammation, including creatine kinase (CK), a muscle enzyme involved in energy metabolism. Decreased serum CK levels have been observed in chronic inflammatory diseases associated with sarcopenia such as rheumatoid arthritis. In turn, CK is increased not only after myocardial infarction and post-traumatic myolysis, but also associated with muscle mass anabolism.ObjectivesTo study the clinical significance of CK levels and their association with other inflammatory and anabolic regulators in frail patients.MethodsWe randomly selected 152 individuals (76 frail and 76 robust) that were 80.86 (±5.49) years and 50% were female, from the second wave of Toledo Study of Healthy Aging cohort (1). CK was measured by routine analysis; serum TNF-α, sgp130, Growth Differentiation Factor (GDF)-15, soluble IL-6R (sIL-6R) and IGF-1 by Multiplex-Luminex. Serum C-Reactive Protein (CRP) and Myostatin (MSTN) were assessed by ELISA. Differences between robust and frail patients were tested using Mann-Whitney and Kruskal-Wallis test for continuous variables and Chi-square test for discrete variables. For each variable, normality was tested using Shapiro-Wilk normality and Kolmogorv-Smirnov tests. Non-normal variables were natural logarithm transformed to achieve normality. The association between each biomarker and frailty was assessed using multivariate logistic models. Additionally, a sensitivity analysis was performed including a second biomarker in the model in order to detect those biomarkers that influenced the association. All analyses were done using R.ResultsInflammatory markers CRP and GDF-15 were increased in frail patients, OR (95% CI) 1.59 (1.22-2.05; p<0,001) and OR 1.93 (1.01-3.68; p=0,006), respectively, in comparison to robust. There were no significant changes in the inflammatory parameters TNF-α, sgp130, sIL-6R between groups. The anabolic marker IGF-1 did not change significantly between groups, while the anti-anabolic mediator MSTN was reduced in frail patients, OR 0.40 (0.19-0.86; p=0.02). Finally, CK levels were decreased in frail patients when compared to robust subjects, OR 0.37 (0.18-0.76; p=0.007). In sensitivity analysis, this association remained statistically significant with ORs ranging from 0.33 to 0.40 regardless of a second biomarker.ConclusionWe identified chronic inflammation in a cohort of frail patients given the significant increase in CRP and GDF-15, although we did not find association with other inflammation parameters such as TNF-α, sgp130 or sIL-6R, highlighting the difficulty of characterize the status of systemic inflammation. The decrease in CK levels in frailty suggest that this marker could be an indicator of cumulative muscle mass loss due to chronic inflammation. Since CRP can be sensitive and altered by a multitude of pathological conditions in frail patients, we propose CK as a more specific marker of inflammation-induced muscle impairment.