Heart Rate Variability and Inflammatory Biomarkers in Patients with CKD

Background: Dysutonomia is common among patients with advanced CKD and is associated with death and cardiovascular (CV) events. Perturbations in sympathovagal balance are hypothesized to contribute to a pro-inflammatory milieu; it is also plausible that inflammation could promote dysautonomia. We explored the association between heart rate variability (HRV; a proxy for dysautonomia) and inflammatory biomarkers among participants of Chronic Renal Insufficiency Cohort (CRIC). Methods: We estimated the association between SDNN (standard deviation of normal-normal intervals) and inflammatory biomarkers (hs-CRP, fibrinogen, IL-6, IL-10, TNF-α, TGF-β, IL-1RA, and IL-1β) through adjusted linear regression. We considered exposures and outcomes continuously (log-transformed) and categorically (quartiles). We adjusted for demographics, comorbidities, laboratory parameters and CV medications. Results: Of the 3,166 included participants, mean age was 57±11 years, 46% were women, mean eGFR was 45±15mL/min/1.73m2; median SDNN was 15 [8,25]. In adjusted models, higher vs. lowest quartiles of SDNN were significantly associated with lower hs-CRP, fibrinogen, IL-6, TNF-α, and IL-1RA; no significant associations were noted with IL-10, TGF-β, or IL-1β. We noted similar patterns when log-SDNN was considered as a continuous variable (Table 1). When SDNN was considered as the outcome, we observed that higher concentrations of hs-CRP, fibrinogen, and IL-6 were associated with lower SDNN (Table 2). Conclusion: Among CRIC participants, SDNN, a surrogate for better autonomic function, was inversely associated with several inflammatory biomarkers. Conversely, multiple inflammatory biomarkers were inversely associated with SDNN. Further investigations are required to delineate the mechanistic pathways linking inflammation and dysautonomia.