Assessment of the autonomic nervous system through the study of cardiovascular autonomic reflexes and their association with inflammation in three clinical settings.

Abstract

Heart Rate Variability describes the beat-to-beat variation in heart rate arising from activity of the sympathetic and parasympathetic branches of the Autonomic Nervous System (ANS). Reduced ANS tone measured by reduced heart rate variability (HRV) is a powerful predictor of adverse diagnosis in patients and is associated with increased mortality. Published research suggests that inflammation has a deleterious effect on Autonomic Nervous System tone. This study aimed to: establish if mild inflammatory conditions are associated with changes in autonomic tone as defined by heart rate variability studies in the following conditions: a. Influenza vaccination b. Reduction in oesophageal inflammation c. Reduction in weight The aim of the first study was to assess the link between inflammation resulting from the influenza vaccination and the associated changes on heart rate variability. 71 healthy volunteers opting to have a routine influenza vaccination were investigated for potential changes in cardiovascular autonomic tone associated with the temporary inflammatory effects of an Influenza vaccination. A number of temporal and frequency domain parameters of heart rate and breathing were assessed 2-5 days prior to vaccination and 1-4 days post vaccination. A sub-group of 15 volunteers who reported significant symptomatic reaction to the vaccination for at least 24 hours following vaccination displayed a statistically significant (p=<0.02) reduction in five of the six HRV parameters obtained during metronome-guided breathing. There was no evidence of significant reduction in autonomic tone following vaccination in the full sample of 71 volunteers. The aim of the second study was to establish whether inflammation resulting from erosive or non-erosive oesophagitis caused by gastro-oesophageal reflux disease had any association with changes in heart rate variability. 12 volunteers with non-erosive oesophageal reflux disease (NERD) and 8 with erosive oesophageal reflux disease (ERD) were investigated for HRV after initial diagnosis under gastroscopy. HRV assessment was repeated following 8 weeks of treatment with a proton-pump inhibitor (PPI). Initial reflux symptoms and response to PPI treatment were assessed using the GERD Impact Scale questionnaire. All participants had effective symptom response to treatment and there was no significant difference insymptoms score between NERD and ERD groups. There was a small but statistically significant increase in HRV detected following PPI treatment in the ERD group (p=0.05). The aim of the third study was to assess the link between obesity / pro-inflammatory adiposity, weight loss and the associated changes in heart rate variability. 38 clinically obese volunteers (BMI 30-39) with a family history of diabetes were reviewed for HRV prior to and following a lifestyle intervention designed to reduce body weight and BMI. Volunteers underwent repeated HRV studies after 4 months and 8 months of treatment. Volunteers on average achieved a weight loss of 11.5% (±6.0). There were statistically significant changes in HRV parameters in sub-group A (BMI ≥36) and correlation of biochemical measures with weight loss. These results further elucidate the effect of mild inflammatory triggers on autonomic tone as measured by HRV. These effects and their significance are discussed in detail in this document. The significance of the ‘cholinergic anti-inflammatory pathway’ is discussed with respect to the inflammatory conditions investigated. Suggestions for further work are proposed. In conclusion it is entirely possible to measure subtle changes in heart rate variability associated with mild inflammation and that on the evidence presented here these changes in heart rate variability are hypothesised to be reversible. My original contribution to knowledge is: 1. Changes in heart rate variability are associated with low grade inflammation resulting from the Influenza vaccination, erosive oesophagitis and increased adiposity. 2. Measurement of subtle changes in autonomic tone, associated with inflammatory challenges is possible and concurs with other published research. 3. The level of HRV attenuation does appear to be linked to those with a higher level of inflammation. In each study the most significant results came from subgroups of volunteers either demonstrating: a higher level of symptom severity, erosive oesophagitis or were in a subgroup of participants with the highest BMI / adipose tissue. 4. In the early stages of reduced heart rate variability we see that concurrent reduction in inflammation is associated with an increase in autonomic tone.