Background/Purpose: We have previously observed associations between systemic lupus erythematosus (SLE) disease activity and heart rate variability (HRV) between 2 time points (1). We aim to prospectively test the hypothesis that HRV reflects longitudinal changes in clinical status and patient reported outcomes.

Methods: HRV was evaluated using a 5 min ECG in SLE patients who completed a minimum of 2 visits in an ongoing clinical trial. HRV parameters were calculated in the time domain (RMSSD and pNN50) and frequency domain [high frequency (HF), low to high frequency (LF/HF) ratio]. A mixed effects linear model with generalized estimating equations was used to compare changes in HRV between paired visits and to examine linear associations between HRV and clinical scores. All models were adjusted for baseline HRV.

Results: Forty nine patients (age 44.9 ± 11.7, 46 female) were followed in 413 paired visits (median time between visits 1 month). BILAG was inversely associated with RMSSD (β=-1.39±0.01; p<0.0001). BILAG, SLEDAI and PGA were directly associated with the LF/HF ratio (β=0.96±0.02; p<0.0001, 0.42±0.10; p<0.0001 and 0.83±0.09; p<0.0001, respectively). Changes in BILAG were inversely associated with changes in RMSSD and pNN50 (β=-7.0±1.9; p=0.003 and -1.6±0.04; p<0.0001, respectively). BILAG changes were also directly associated with changes in the LF/HF ratio (β=0.78±0.05; p<0.0001). Categorical improvement (≥1 letter grade improvement in BILAG and no new BILAG A/B) occurred in 77 (19%) visit pairs (group 1) and no improvement or worsening in 335 (81%) (group 2). RMSSD and HF increased in group 1 vs. group 2 (group difference=-33.3±10.1; p=0.001 and -30.9±4.1; p<0.0001, respectively), and the LF/HF ratio decreased in group 1 vs. group 2 (group difference=3.1±0.8; p=0.002). The average per visit changes in HRV in groups 1 and 2 are listed in Table 1.

Changes in Physical Component Summary (PCS) of SF36v2 were inversely related to changes in SLEDAI and PGA (β=-0.39±0.14; p=0.006 and -0.19±0.02; p<0.0001, respectively). Changes in Mental Component Summary (MCS) were inversely related to changes in BILAG, SLEDAI and PGA (β=-0.23±0.07; p=0.0001, -0.31±0.10; p=0.002 and -0.08±0.03; p=0.008, respectively). PCS was related to HF (β=0.67±0.28, p=0.01) and MCS was inversely related to the LF/HF ratio (β=-0.11±0.03, p=0.0001). Changes in PCS were related to changes in pNN50 (β=0.21±0.05, p=0.0001) and LF/HF (β=0.17±0.06, p=0.003) and changes in MCS were related to changes in HF (β=1.57±0.18; p<0.0001).

Conclusion: Changes in HRV reflect changes in clinical status and patient reported outcomes in patients with SLE. These data suggest that HRV may be a simple non-invasive tool used to gage or predict clinical improvement in SLE. Further studies are warranted.

Table 1. Average per visit changes in HRV in groups 1 and 2.

References: 1. Thanou A, Stavrakis S, Dyer JW, Munroe ME, James JA, Merrill JT. Arthritis Res Ther. 2016 Sep 2;18:197.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/changes-in-heart-rate-variability-reflect-changes-in-clinical-status-and-patient-reported-outcomes-in-systemic-lupus-erythematosus-a-longitudinal-analysis/