The Associations of Heart Rate Variability with Inflammatory Biomarkers

Introduction Autonomic dysfunction is common among patients with advanced chronic kidney disease (CKD) and is associated with death and cardiovascular (CV) events. Perturbations in sympathovagal balance are hypothesized to contribute to a pro-inflammatory milieu; however, inflammation could adversely affect autonomic function. Methods Using the Chronic Renal Insufficiency Cohort (CRIC) study, we estimated the associations among SDNN (standard deviation of normal-normal intervals) and RMSSD (root mean square of successive differences between R-R intervals) and a composite inflammation score representing abnormal values of five plasma inflammatory biomarkers, as well as with individual biomarkers (hs-CRP, fibrinogen, IL-6, TNF-α , and IL-1β). We considered all independent and dependent variables ("exposures and outcomes") continuously (log-transformed) and categorically (by quartiles). We adjusted for demographic, clinical and relevant laboratory covariates. Results Among 3,166 CRIC participants, mean age 57 ±11 years, 46% women, and mean eGFR 45 ±15mL/min/1.73m 2 ; median [25 th , 75 th percentile]. SDNN was 15 [8, 25]ms and median RMSSD was 17 [9, 29]ms. SDNN and RMSSD were inversely related to the composite inflammation score and to plasma concentrations of component biomarkers. In adjusted analyses, for each integer increase in the composite inflammation score, SDNN was 5% (95% confidence limit (95% CI 3%, 8%) lower and RMSSD 6% (95% CI 3%, 8%) lower. Results were consistent across analyses when incorporating log-transformed values of individual biomarkers. Conclusion In CRIC, SDNN and RMSSD, surrogates for autonomic function were inversely associated with a composite inflammation score and individual inflammatory biomarkers. Future work should delineate mechanistic pathways linking inflammation and autonomic dysfunction in CKD.