Author + information
- Stavros Stavrakis, MD, PhD,
- Mary Beth Humphrey, MD, PhD and
- Sunny S. Po, MD, PhD∗ ()
- ↵∗Heart Rhythm Institute, University of Oklahoma Health Sciences Center, 1200 Everett Drive, TCH 6E103, Oklahoma City, Oklahoma 73104
We thank Dr. Machhada and colleagues for their insightful comments regarding the effects of low-level tragus stimulation (LLTS) on C-reactive protein (CRP). Although the CRP levels appear to be non-normally distributed in the LLTS group, the assumptions of constant variance and normality were reasonable for this model on the basis of the residual plots, as pointed out in the statistical methods of our paper (1). In addition, in our statistical model we did control for baseline CRP levels. The final results thus reflect the effect of LLTS after adjustment for baseline CRP levels.
Atrial fibrillation is characterized by systemic inflammation, which is supported by the elevated levels of inflammatory cytokines, including tumor necrosis factor (TNF)-α and CRP, in our patient population (1). Importantly, the magnitude of decrease in inflammatory cytokine levels by LLTS is consistent with the difference between controls and pre–rheumatoid arthritis patients (1). This effect is unlikely the result of anesthesia or body mass index, both of which have been shown to affect CRP levels (2), given that the exposure of the control and experimental groups to each of these factors was balanced between the 2 groups. We cannot comment on the exact time course of CRP in our study, as we did not obtain serial measurements of CRP. The plasma half-life of CRP was determined in ambulatory healthy volunteers (3). It is unknown whether anesthesia affects the plasma half-life of CRP. However, a recent study showed that anesthesia significantly decreased CRP transiently 30 min post-operatively compared with pre-operative levels (2). It should be noted that the anti-inflammatory effect of LLTS on TNF-α is consistent with its half-life of approximately 18 min (4). In addition, other studies have shown a significant decrease in TNF-α after just 20 min of vagus nerve stimulation (5). In summary, the overall results of our study support the notion that vagal stimulation modulates inflammation.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation