Longitudinal changes and prognostic significance of cardiovascular autonomic regulation assessed by heart rate variability and analysis of non-linear heart rate dynamics

Vesa Jokinen

Department of Internal Medicine, University of Oulu

Abstract

Several studies have shown that altered cardiovascular autonomic regulation is associated with hypertension, diabetes, aging, angiographic severity of coronary artery disease (CAD), and increased mortality after acute myocardial infarction (AMI). The purpose of this study was to assess the temporal changes and prognostic significance of various measures of heart rate (HR) behaviour and their possible associations to coronary risk variables, and the progression of CAD in different populations.

This study comprised five patient populations. The first consisted of 305 patients with recent coronary artery bypass graft surgery (CABG) and lipid abnormalities, the second of 109 male patients with recent CABG, the third of 53 type II diabetic patients with CAD, the fourth of 600 patients with recent AMI, and the fifth of 41 elderly subjects. HR variability and non-linear measures of HR dynamics were analysed.

Among the patients with prior CABG, a significant correlation existed between the baseline HR variability (standard deviation of N-N intervals, SDNN) and the progression of CAD (r = 0.26, p < 0.001)). In the longitudinal study of patients with prior CABG, only the fractal indexes of HR dynamics, such as the power law slope (β) and the short-term fractal exponent (α1), decreased significantly. In diabetic patients, SDNN decreased significantly (p < 0.001) during the three-year period. The reduction of SDNN was related to cholesterol, triglyceride, and glucose levels, and also to progression of CAD (r = 0.36, p < 0.01). In the longitudinal follow-up study of patients with recent AMI, reduced fractal indices (α1 and β), and reduced HR turbulence predicted cardiac death when measured at the convalescent phase after AMI. Reduced β and turbulence slope predicted cardiac death when measured at 12 months after AMI. In the elderly population, β (p < 0.001) and α1 (p < 0.01) reduced significantly. Low-frequency power spectra were the only traditional measure of HR variability that decreased significantly during the 16-year period.

HR variability is associated with many risk factors of atherosclerosis and with progression of CAD among patients with ischemic heart disease. Fractal HR dynamics are more sensitively able to detect age-related changes in cardiovascular autonomic regulation. Altered fractal HR dynamics and HR turbulence are associated with increased mortality after AMI.


Dedication

You'll never walk alone

(The theme of Liverpool F.C. since 1892)

Table of Contents
Acknowledgements
Abbreviations
List of original communications
1. Introduction
2. Review of the literature
2.1. Risk factors of coronary artery disease
2.2. Progression of coronary artery disease
2.3. Traditional measures of heart rate variability
2.3.1. Time domain measures of heart rate variability
2.3.2. Frequency domain measures of heart rate variability
2.4. Non-linear analysis of heart rate dynamics
2.4.1. Detrended fluctuation analysis
2.4.2. Power law relationship analysis of heart rate dynamics
2.4.3. Approximate entropy analysis
2.4.4. Heart rate turbulence analysis
2.5. Reproducibility of measures of heart rate variability and heart rate dynamics
2.6. Physiological background of heart rate variability and heart rate dynamics
2.7. Correlations between different measures of heart rate variability and heart rate dynamics
2.8. Heart rate variability and heart rate dynamics in different populations
2.8.1. Heart rate variability and heart rate dynamics in uncomplicated CAD
2.8.2. Heart rate variability after AMI
2.8.3. Heart rate variability and diabetes
2.8.4. Heart rate variability and heart rate dynamics after CABG
2.8.5. Heart rate variability and heart rate dynamics in aging subjects
2.8.6. Heart rate variability in other diseases
2.8.7. Effects of medication on heart rate variability
2.9. Temporal changes in heart rate variability
2.10. Prognostic significance of heart rate variability and heart rate dynamics
3. Purpose of the present study
4. Patients
5. Methods
5.1. Clinical and laboratory analysis
5.2. Echocardiographic measurements
5.3. Angiographic data
5.4. Analysis of heart rate variability and heart rate dynamics
5.4.1. Time and frequency domain measures
5.4.2. Detrended fluctuation analysis
5.4.3. Power law relationship analysis
5.4.4. Approximate entropy analysis
5.4.5. Heart rate turbulence analysis
5.5. Statistics
6. Results
6.1. Baseline characteristics of heart rate variability and heart rate dynamics in the study groups
6.2. Heart rate variability and progression of atherosclerosis
6.3. Temporal changes in heart rate variability and heart rate dynamics after CABG
6.4. Prognostic significance and temporal changes in heart rate variability and heart rate dynamics in type II diabetes
6.5. Prognostic significance and temporal changes in heart rate variability and heart rate dynamics after AMI
6.6. Temporal changes in heart rate variability and heart rate dynamics in elderly subjects
7. Discussion
7.1. Heart rate variability and progression of atherosclerosis
7.2. Temporal changes in heart rate variability and heart rate dynamics after CABG
7.3. Temporal changes in heart rate variability, heart rate dynamics, and progression of CAD in type II diabetes
7.4. Prognostic power and temporal changes in heart rate variability and heart rate dynamics after AMI
7.5. Temporal changes in heart rate variability and heart rate dynamics in elderly subjects
7.6. Methodogical limitations
8. Conclusions
References
List of Tables
1. Baseline characteristics of the patient populations (mean(SD or %)).
2. The baseline values of HR dynamics in all study groups (means (SD)).
3. The changes in HR variability and HR dynamics during the 3-year period. Means (SD).
4. The measures of HR variability and HR dynamics in diabetic subjects at baseline and after 3 years. Means (SD).
5. Baseline indices of HR variability and HR dynamics of post-AMI patients as predictors of subsequent mortality.
6. Temporal changes in the measures of HR variability and HR dynamics after acute myocardial infarction (n = 416). Means (SD).
7. HR variability and HR dynamics in post-AMI patients measured at 12 months as predictors of subsequent mortality.
8. Temporal changes of HR variability and HR dynamics in elderly subjects after 16 years of follow-up.
List of Figures
1. Per-patient changes in the CABG study group in the minimum luminal diameter of stenoses in all native coronary arteries of the patients divided into tertiles according to the SDNN measured in 12-hour electrocardiography. Values are mean  SEM.
2. Kaplan-Meier survival curves for the different parameters of HR variability and HR dynamics at the convalescent phase after acute myocardial infarction. Patients with non-cardiac death were excluded from the analysis. A. Standard deviation of N-N intervals (SDNN). B. Turbulence slope. C. Power law slope. D. Short-term fractal exponent.
3. Kaplan-Meier survival curves for different parameters of HR variability and HR dynamics measured at one year after acute myocardial infarction. Patients with non-cardiac death were excluded from the analysis. A. Standard deviation of N-N intervals (SDNN). B. Turbulence slope. C. Power law slope. D. Short-term fractal exponent.
4. An example of the power spectra of heart rate variability (upper), power law slope (β ) (middle), and short-term fractal exponent (α1) at the baseline recording (left) and 16 years after the baseline (right). LF = low-frequency.