Phase angle as a marker of muscle quality: A systematic review and meta-analysis.

Background & Aims: Phase angle (PhA) is a biomarker derived from raw bioelectrical impedance analysis (BIA) values: resistance (R) and reactance (Xc). PhA reflects cellular membrane integrity and, as a result, has been considered a marker of fluid distribution, making it a potential prognostic indicator. A growing body of research demonstrates independent associations between PhA and muscle strength, mass, and composition. In this context, PhA has the extra potential to serve as a marker of muscle quality. However, the evidence supporting its use for this purpose is not well established. This study aimed to investigate the relationship between PhA and markers of muscle quality.

Methods: This systematic review and meta-analysis (Internal Prospective Register of Systematic Reviews - PROSPERO on a registration code: CRD42024507853) focused on observational studies assessing the relationship between PhA and markers of both concepts of muscle quality: the muscle quality index (MQI: strength by a unit of mass) and the muscle composition (i.e., skeletal muscle radiodensity [SMD], muscle echogenicity, muscle fat fraction, inter- and intramuscular adiposity). Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), while the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Meta-analyses with a random-effects model were conducted.

Results: Seventeen studies were included in this systematic review, encompassing 2710 participants. Meta-analyses demonstrated that PhA had a moderate positive correlation coefficient with SMD (4 studies, 924 participants; r = 0.54, 95 % confidence interval (CI) 0.38 to 0.69, heterogeneity (I) = 92 %) and good accuracy (85 %) for classifying low SMD (2 studies, 390 participants; Area Under the Curve - AUC 0.85, 95 % CI 0.78 to 0.92, I = 0 %). PhA was inversely-moderately correlated with muscle echogenicity (8 studies, 1401 participants; r = - 0.42, 95 % CI - 0.57 to - 0.24, I = 82 %) and positively-weakly correlated with MQI (2 studies, 191 participants; r = 0.36, 95 % CI 0.21 to 0.49, I = 17 %). All studies had a higher risk of bias. The certainty of evidence ranged from low to very low.

Conclusion: Despite technical challenges, this study demonstrates the potential of PhA as a surrogate marker for muscle quality, particularly expressing muscle composition (SMD). Future studies should utilize BIA with standardized protocols to potentially establish specific cutoff values for PhA, thereby enhancing its diagnostic accuracy and clinical applicability. These studies could additionally explore the mechanisms underlying the associations between PhA and muscle quality aspects. In cases where technical factors are not easily controlled, the use of standardized PhA (SPhA), which converts PhA into Z-scores, could be beneficial. Although this warrants investigation, this approach (SPhA) has the potential to account for variables such as age, sex, device differences, and health status.