Predictors of heart rate variability and its prognostic significance in chronic kidney disease

Abstract

Background: Heart rate variability (HRV), a noninvasive measure of autonomic dysfunction and a risk factor for cardiovascular disease (CVD), has not been systematically studied in nondialysis chronic kidney disease (CKD).

Methods: HRV was assessed using 24-h Holter monitoring in 305 subjects from the Renal Research Institute-CKD Study, a four-center prospective cohort of CKD (Stages 3-5). Multiple linear regression was used to assess predictors of HRV (both time and frequency domain) and Cox regression used to predict outcomes of CVD, composite of CVD/death and end-stage renal disease (ESRD).

Results: A total of 47 CVD, 67 ESRD and 24 death events occurred over a median follow-up of 2.7 years. Lower HRV was significantly associated with older age, female gender, diabetes, higher heart rate, C-reactive protein and phosphorus, lower serum albumin and Stage 5 CKD. Lower HRV (mostly frequency domain) was significantly associated with higher risk of CVD and the composite end point of CVD or death. Significantly, lower HRV (frequency domain) was associated with higher risk of progression to ESRD, although this effect was relatively weaker.

Conclusions: This study draws attention to the importance of HRV as a relatively under recognized predictor of adverse cardiovascular and renal outcomes in patients with nondialysis CKD. Whether interventions that improve HRV will improve these outcomes in this high-risk population deserves further study.

Figures

Fig. 1.

Patient recruitment flow into the CV substudy of the RRI-CKD study (n = 305).

Fig. 2.

Comparisons of HRV parameters among this CKD cohort (dark gray) and healthy controls [10] (white). Bars and whiskers represent the mean ± SD.

Fig. 3.

Impact of HRV parameters on risk of CVD events. Hazard ratios and 95% confidence intervals associated with increases in HRV parameters, after adjustment for age, history of CVD events, gender, serum phosphorus and albumin, are presented. Measures marked with an asterisk are plotted on the log scale.

Fig. 4.

The cumulative probability of CVD events over time since Holter monitoring by LF/HF ratio (most predictive measure) above and below the median. An LF/HF ratio below the median (