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Abstract Number: 866

Heart Rate Variability: An Inflammatory Biomarker in Systemic Lupus Erythematosus

Aikaterini Thanou1, Stavros Stavrakis2, John Dyer2, Stan Kamp3, Melissa E. Munroe4, David Albert5, Judith A. James6 and Joan T. Merrill3, 1Arthritis and Clinical Immmunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 2Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 3Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 4Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 5AliveCor, Inc., San Francisco, CA, 6Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK

Meeting: 2014 ACR/ARHP Annual Meeting

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

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Session Information

Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment: Cardiovascular Disease and Pregnancy

Session Type: Abstract Submissions (ACR)

Background/Purpose: Heart rate variability (HRV) is a marker of vagus nerve activity and can be easily obtained with minimal technical expertise in the outpatient setting, using software calculating the distance between consecutive R waves on the electrocardiogram tracing. Decreased HRV is strongly associated with cardiovascular morbidity and mortality, and measures of HRV have been inversely correlated with inflammatory biomarkers in the general population. The current study evaluates the relationship of HRV with clinical disease activity and cytokine pathways in patients with systemic lupus erythematosus (SLE).

Methods: 58 patients with SLE from the Oklahoma Lupus Cohort were evaluated at two visits with the stipulation that there must be at least mild/moderate disease activity, in the clinician’s opinion, at the first visit. Standard of care was rendered to each patient per usual clinic practice. Clinical assessments included the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the British Isles Lupus Assessment Group (BILAG 2004) index and the Physician Global Assessment (PGA). A 5-minute ECG was obtained at each visit for HRV analysis using the AliveCor iPhone ECG device. Serum cytokine levels, including interleukin 6 (IL-6) and B Lymphocyte Stimulator (BLyS) were measured with an enzyme-linked immunoassay (ELISA). Linear regression analysis and multivariate linear mixed effect models were used.

Results: At baseline, mean SLEDAI was 7.6±0.3, mean cumulative BILAG 2004 index was 10.0±0.6 and mean PGA was 1.4±0.1. Baseline HRV measures were negatively associated with baseline disease activity using the BILAG 2004 index (p=0.01), but less consistently with the SLEDAI score (p=0.60) and the PGA (p=0.16). HRV measures were also negatively associated with baseline IL-6 levels (p=0.02). At the follow up visit (median 1 month from the baseline visit), there was a significant decrease in SLEDAI (average decrease -2.3±0.5), BILAG 2004 index (average decrease -3.7±1.0) and PGA (average decrease -0.4±0.1) compared to baseline. Change in HRV measures was negatively associated with change in the BILAG 2004 index (p=0.03) and the PGA (p=0.02) and less well with change in SLEDAI (p=0.12), indicating that an increase in HRV is associated with a favorable change (decrease) in disease activity at follow up. In addition, there was a significant association between the change in HRV measures and improvement in IL-6 (p=0.04) and BLyS (p=0.03). None of the disease activity indices were correlated with change in IL-6 levels (p>0.05 for each); however, the change in BLyS levels was positively associated with change in SLEDAI (p=0.03) and BILAG 2004 index (p=0.02). 

Conclusion: These pilot findings suggest that HRV measures could provide a sensitive marker for lupus disease activity and improvement, and support a role for HRV as an easily measured, non-invasive, in- office procedure. Its relevance to specific clinical or immunologic phenotypes or potential utility as a treat to target endpoint remain to be further explored.


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.

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