Clinical Evidence of Wearable-Derived Heart Rate Variability for Detecting Systemic Inflammation: A Systematic Review

Background/Objectives: Wearable devices capable of capturing heart rate variability (HRV) enable continuous assessment of autonomic nervous system function in real-world settings. Because systemic inflammation disrupts autonomic balance through vagal withdrawal and sympathetic activation, HRV has been proposed as a non-invasive digital biomarker of inflammatory activity. Despite the rapid expansion of wearable sensor technologies, the accuracy and consistency for detecting systemic inflammatory states remain unclear. This systematic review aimed to evaluate the clinical relevance of wearable-derived HRV indices in relation to established inflammatory biomarkers. Methods: A systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library was conducted through April 2025. Due to methodological heterogeneity, findings were synthesized using the Synthesis Without Meta-analysis (SWiM) framework with vote counting, effect-direction plots, and sign tests. Results: Eleven studies involving 2419 participants met the inclusion criteria. Vote counting demonstrated that SDNN showed a predominantly inverse association with CRP, with 83% of comparisons indicating reduced SDNN in the presence of elevated CRP (sign test p = 0.031). In contrast, associations between RMSSD and inflammatory cytokines were heterogeneous and largely non-significant. ECG-based wearable devices yielded more consistent associations than photoplethysmography-based devices, while recording duration and population characteristics contributed to variability across studies. Conclusions: Wearable-derived HRV, particularly SDNN from ECG-based devices, shows a consistent inverse association with CRP, supporting its role as a non-invasive physiological correlate of systemic inflammation. However, heterogeneity and the lack of diagnostic accuracy metrics limit conclusions regarding clinical utility. At present, wearable HRV should be considered an exploratory or adjunctive biomarker, pending validation in standardized longitudinal studies with formal diagnostic performance assessment.