Wearable ECG-derived SDNN showed a consistent inverse association with CRP in adults with systemic inflammation, with 83% of studied comparisons indicating reduced SDNN with elevated CRP (sign test p=0.022).
Systematic Review (n=2,419)
Does wearable-derived heart rate variability accurately correlate with established systemic inflammatory biomarkers?
Wearable-derived HRV, particularly SDNN from ECG-based devices, shows a consistent inverse association with CRP, suggesting potential as an exploratory non-invasive biomarker for systemic inflammation.
Effect estimate: Proportion of studies showing inverse association for SDNN and CRP: 83% (sign test p=0.022) (95% CI 95% CI 0.36–1.00 for SDNN and CRP inverse association)
p-value: p=0.022
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.
Siswishanto et al. (Wed,) conducted a systematic review in Adults (≥18 years) with diagnosed or suspected systemic inflammation across diverse clinical contexts including acute inflammatory responses, chronic inflammatory states, and experimental endotoxemia (n=2,419). Wearable-derived heart rate variability monitoring vs. Established inflammatory biomarkers (e.g., CRP, IL-6, TNF-α) was evaluated on Association between wearable-derived HRV indices (SDNN, RMSSD) and established systemic inflammatory biomarkers (primarily CRP) (Proportion of studies showing inverse association for SDNN and CRP: 83% (sign test p=0.022), 95% CI 95% CI 0.36–1.00 for SDNN and CRP inverse association, p=0.022). Wearable ECG-derived SDNN showed a consistent inverse association with CRP in adults with systemic inflammation, with 83% of studied comparisons indicating reduced SDNN with elevated CRP (sign test p=0.022).