Association of heart rate variability and inflammatory response in patients with cardiovascular diseases: current strengths and limitations

Abstract

Many experimental and clinical studies have confirmed a continuous cross-talk between both sympathetic and parasympathetic branches of autonomic nervous system and inflammatory response, in different clinical scenarios. In cardiovascular diseases, inflammation has been proven to play a pivotal role in disease progression, pathogenesis and resolution. A few clinical studies have assessed the possible inter-relation between neuro-autonomic output, estimated with heart rate variability analysis, which is the variability of R-R in the electrocardiogram, and different inflammatory biomarkers, in patients suffering from stable or unstable coronary artery disease (CAD) and heart failure. Moreover, different indices derived from heart rate signals' processing, have been proven to correlate strongly with severity of heart disease and predict final outcome. In this review article we will summarize major findings from different investigators, evaluating neuro-immunological interactions through heart rate variability analysis, in different groups of cardiovascular patients. We suggest that markers originating from variability analysis of heart rate signals seem to be related to inflammatory biomarkers. However, a lot of open questions remain to be addressed, regarding the existence of a true association between heart rate variability and autonomic nervous system output or its adoption for risk stratification and therapeutic monitoring at the bedside. Finally, potential therapeutic implications will be discussed, leading to autonomic balance restoration in relation with inflammatory control.

Keywords: autonomic nervous system; cardiovascular disease; coronary artery disease; heart rate variability; inflammation; mortality.

Figure 1

(A) Longitudinal trends over time of mean values of CRP and LF/HF ratio, reflecting sympathovagal balance, for patients with SOFA > 10, during the 6 days of study period. [log transformed data, adapted from Papaioannou et al. (2009)]. It appears that LF/HF changes inversely with CRP. (B) Longitudinal trends over time of mean values of CRP and SDNN (secs), for patients with SOFA > 10, during the 6 days of study period. [log transformed data, adapted from Papaioannou et al. (2009)]. There is a progressive increase in SOFA score from day 1 until day 4 (development of septic shock) and a subsequent downward shift in its values. At the same time, the variability of heart rate signals estimated with SDNN seems to be significantly reduced during the development of septic shock.