Heart Rate Variability New Window in Lupus Disease Activity

Pam Harrison

December 01, 2014

Heart rate variability appears to reflect levels of disease activity in patients with systemic lupus erythematosus, according to research presented at the American College of Rheumatology 2014 Annual Meeting in Boston.

"Although this is a very preliminary examination of this marker, heart rate variability can be measured noninvasively on an electrocardiogram and it offers a new way of evaluating disease activity in these patients, which is why we think it is important," said Katherine Thanou, MD, from the Oklahoma Medical Research Foundation in Oklahoma City.

Investigators evaluated 58 patients with systemic lupus erythematosus from the Oklahoma Lupus Cohort during a baseline and follow-up visit. At the baseline visit, patients had at least mild to moderate disease activity.

The Systemic Lupus Erythematosus Disease Activity index (SLEDAI), the British Isles Lupus Assessment Group (BILAG 2004) disease activity index, and the Physician Global Assessment (PGA) were used to assess disease activity.

At both visits, patients underwent a 5-minute electrocardiogram test, and heart rate variability was analyzed with the AliveCor Heart Monitor iPhone device. The device calculates the distance between consecutive R waves on the ECG tracing.

Serum cytokine levels, notably measures of interleukin (IL)-6 and B lymphocyte stimulator, were measured with an enzyme-linked immunosorbent assay at baseline.

Because heart rate variability is a measure of vagus nerve activity, "the higher the vagus nerve output, the higher the heart rate variability," Dr. Thanou explained.

The higher the vagus nerve output, the higher the heart rate variability.

It has been previously shown that measures of variability are inversely correlated with inflammatory biomarkers in the general population.

In this study, Dr. Thanou and colleagues found that baseline heart rate variability measures were significantly and negatively associated with baseline BILAG 2004 scores (P = .01). Baseline variability measures, however, were less consistently associated with the SLEDAI score (P = .60) and the PGA score (P = .16).

Variability measures were also negatively associated with baseline IL-6 levels (P = .02), as expected from observations in the general population.

At the follow-up visit, a median of 1 month after the baseline visit, significant decreases were seen on all measures of disease activity.

Table. Significant Decreases in Disease Activity on Mean Scores

Measure Baseline Visit Follow-up Visit Average Decrease
SLEDAI 7.6 5.3 2.3
BILAG 2004 10.0 6.3 3.7
PGA 1.4 1.0 0.4


At follow-up, heart rate variability measures were negatively associated with changes in BILAG 2004 (P = .03) and PGA (P = .02) scores, but the association was weaker for the SLEDAI score (P = .12).

"This indicates that an increase in heart rate variability was associated with a favorable change in disease activity at follow-up," the investigators report.

Again as expected, there was a significant association between increases in variability measures and improvement in serum cytokine levels of both IL-6 (P = .04) and B lymphocyte stimulator (P = .03).

"We need to further analyze the data and examine how these parameters are related to other cytokines that are relevant to lupus," said Dr. Thanou. "We think that the association between heart rate variability and the changes in disease activity we observed in this study deserves further exploration."

Loss of variability is a measure of autonomic nervous system dysfunction, said Brian Bourke, MD, from St. George's Hospital and University in London, United Kingdom.

In fact, heart rate variability was shown to be statistically associated systemic lupus erythematosus in 1997, and the finding has been reproduced in subsequent studies.

However, "previous studies have failed to establish a statistical relationship with levels of disease activity or duration of disease," Dr. Bourke told Medscape Medical News.

In this study, there was some statistical association between loss of heart rate variability and levels of cytokines. But, he added, "the most sensitive of the three clinical measures of disease activity, namely SLEDAI, was not found to be significantly associated."

"Therefore, more work is needed to establish whether this potentially easy-to-use technique could be useful as a clinical measure of disease activity in systemic lupus erythematosus," Dr. Bourke said.

Dr. Thanou and Dr. Bourke have disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2014 Annual Meeting. Abstract 866. Presented November 16, 2014.


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