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Abstract Number: 1829

Heart Rate Variability Is Associated with SLE Flare and with TNF- and IFN-Mediated Signaling

Aikaterini Thanou1, Stavros Stavrakis2, John Dyer2, Stan Kamp3, Melissa E. Munroe1, David Albert4, Judith A. James5 and Joan T. Merrill3, 1Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 2Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 3Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 4AliveCor, Inc., San Francisco, CA, 5Arthritis and Clinical Immunology, University of Oklahoma Health Sciences Center and Oklahoma Medical Research Foundation, Oklahoma City, OK

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: cytokines and systemic lupus erythematosus (SLE), Disease Activity

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Session Information

Date: Monday, November 9, 2015

Session Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Decreased heart rate variability (HRV), associated with adverse outcomes in cardiovascular diseases, is frequently seen in patients with SLE. The LF/HF ratio, a HRV measure, reflects sympathovagal balance. We examined associations of HRV with SLE activity and cytokine expression.

Methods: 53 SLE patients were evaluated at 2 visits (total 106 visits) with BILAG, SLEDAI, PGA and SFI (SELENA Flare Index). Caffeine, tobacco and medications were recorded. HRV (RMSSD, pNN50, HF, LF/HF ratio) was measured using a 5-minute ECG. Plasma cytokines were assessed by ELISA or a multiplex immunoassay.

Results: Baseline HRV was inversely related to disease activity and flare (table). Changes in HRV between visits were inversely related to changes in SLEDAI and PGA.  Hydroxychloroquine dose was associated with increased HRV. Age, caffeine, tobacco and other medications had no impact. Plasma TNFRII and MIG inversely correlated with baseline HRV, and similar trends were observed for BLyS, IL-1α, IFNα and IP-10. Using multivariate linear regression model with backward elimination, TNFRII was an independent predictor of baseline HRV after adjusting for hydroxychloroquine dose and plasma BLyS, IL-1α and IFNα. In a similar model, MIG impact remained significant adjusting for the same variables. Furthermore, changes in the LF/HF ratio between visits were associated with changes in TNFRII (p=0.048) and MIG (p=0.029).

Conclusion: Impaired HRV, particularly the LF/HF ratio, is associated with lupus disease activity, acute flare state, and several cytokines related to TNF and IFN pathways. The strongest association was with TNFRII and MIG, confirming and expanding previous immune connections to vagal signaling.

p values

Univariate linear regression

Multivariate linear regression

Dependent variables at baseline

Dependent variables at baseline

RMSSD

pNN50

HF

LF/HF

RMSSD

pNN50

HF

LF/HF

 Independent variables at Baseline

BILAG

0.259

0.019

0.02

0.024

 

 

 

 

SLEDAI

0.683

0.312

0.488

0.073

 

 

 

 

PGA

0.651

0.014

0.154

0.062

 

 

 

 

Flare (SFI)

0.456

0.329

0.047

0.008

ns

ns

ns

ns

BLyS

0.778

0.29

0.115

0.071

ns

ns

ns

ns

IL-17A

0.689

0.132

0.174

0.988

 

 

 

 

TNFα

0.361

0.533

0.354

0.903

 

 

 

 

TNFRII

<0.001

0.01

0.039

0.024

<0.001

0.01

0.039

0.024

IL-1α

0.089

0.099

0.254

0.485

ns

ns

ns

ns

IFNα 

0.420

0.076

0.272

0.124

ns

ns

ns

ns

MIG

0.007

0.015

0.018

0.026

0.007

0.015

0.018

0.026

IP-10

0.202

0.088

0.122

0.189

 

 

 

 


Disclosure: A. Thanou, None; S. Stavrakis, None; J. Dyer, None; S. Kamp, None; M. E. Munroe, None; D. Albert, AliveCor, Inc.., 3; J. A. James, None; J. T. Merrill, None.

To cite this abstract in AMA style:

Thanou A, Stavrakis S, Dyer J, Kamp S, Munroe ME, Albert D, James JA, Merrill JT. Heart Rate Variability Is Associated with SLE Flare and with TNF- and IFN-Mediated Signaling [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/heart-rate-variability-is-associated-with-sle-flare-and-with-tnf-and-ifn-mediated-signaling/. Accessed January 17, 2021.
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