Evaluating the Clinical Accuracy of Wearable HRV Devices in Inflammation Monitoring: A Systematic Review (Preprint)

BACKGROUND Systemic inflammation is a key contributor to many chronic and acute diseases, yet its monitoring often requires invasive procedures. Heart rate variability (HRV), a non-invasive marker of autonomic nervous system function, has shown potential as a surrogate indicator of inflammation. With wearable devices now capable of continuous HRV monitoring, their clinical validity for inflammation detection requires systematic evaluation. OBJECTIVE This systematic review aims to evaluate the clinical accuracy of wearable devices in monitoring systemic inflammation by examining the association between heart rate variability (HRV) indices specifically SDNN and RMSSD and inflammatory biomarkers such as C-reactive protein (CRP), interleukins, and TNF-α across diverse inflammatory conditions. The goal is to assess the consistency and direction of associations and to explore the potential of wearable HRV monitoring as a non-invasive tool for inflammation detection. METHODS A systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library was conducted (April 2025). Studies were eligible if they compared wearable-derived HRV parameters to inflammatory biomarkers (CRP, IL-6, IL-10, TNF-α). Risk of bias was assessed using QUADAS-2. Synthesis followed the SWiM guideline, employing vote counting and effect direction plots. RESULTS Eleven studies (n = 2,419) were included. Most studies found an inverse association between SDNN and CRP (83%; p = 0.031), while associations with cytokines (IL-6, IL-10, TNF-α) were inconsistent. RMSSD showed mixed results. Device type, recording duration, and population characteristics contributed to heterogeneity. CONCLUSIONS Wearable-derived HRV, especially SDNN, shows promise as a non-invasive marker of systemic inflammation, particularly for CRP. However, further research is needed to establish clinical utility and standardize measurement protocols. CLINICALTRIAL PROSPERO registration number CRD420251029821