Cardiovascular Disease Risk after Spinal Cord Injury: The Role of Autonomic Dysfunction

140 Pages·2013·10.43 MB·English

by  Rianne Ravensbergen

Cardiovascular Disease Risk after
Spinal Cord Injury:
The Role of Autonomic Dysfunction
by
Henrike Joanna Cornelie (Rianne) Ravensbergen
M.Sc., Free University Amsterdam, 2005
Thesis Submitted in Partial Fulfillment of the
Requirements for the Degree of
Doctor of Philosophy
in the
Department of Biomedical Physiology and Kinesiology
Faculty of Science
© Henrike Joanna Cornelie (Rianne) Ravensbergen 2013
SIMON FRASER UNIVERSITY
Summer 2013
Approval
Name: Henrike Joanna Cornelie (Rianne) Ravensbergen
Degree: Doctor of Philosophy
Title of Thesis: Cardiovascular Disease Risk after Spinal Cord
Injury: The Role of Autonomic Dysfunction
Examining Committee: Chair: Angela Brooks-Wilson
Associate Professor
Victoria Claydon
Senior Supervisor
Assistant Professor
Department of Biomedical Physiology
and Kinesiology
Scott Lear
Supervisor
Professor
Department of Biomedical Physiology
and Kinesiology
Shubhayan Sanatani
Supervisor
Associate Professor
Department of Pediatrics
Faculty of Medicine, University of
British Columbia
Will Cupples
Internal Examiner
Professor
Department of Biomedical Physiology
and Kinesiology
Vaughan Macefield
External Examiner
Professor
School of Medicine
University of Western Sydney

Date Defended/Approved: August 7, 2013

ii
Partial Copyright Licence

iii
Abstract
Cardiovascular disease (CVD) is the leading cause for mortality and morbidity in those
with spinal cord injury (SCI), with an earlier onset and more rapid progression compared
to the general population. Lifestyle changes after injury have been suggested to be the
main contributor to CVD risk, but I proposed that the issue is more complicated.
Although less well-known, autonomic function is affected by SCI, in addition to motor
and sensory dysfunction. Cardiovascular autonomic dysfunction is a particular concern in
individuals with high lesions (above T5) due to the possible disruption of descending
spinal sympathetic pathways to the heart and main vascular resistance bed. In this
thesis, I propose that cardiovascular autonomic impairment plays a role in the elevated
CVD risk. The thesis starts with an evaluation of the prevalence and progression of
cardiovascular dysfunction after SCI. Then, the contribution of autonomic dysfunction on
CVD risk is investigated. In addition, markers for obesity-related CVD risk specific to
individuals with SCI and ECG markers for cardiac arrhythmias in relation to autonomic
impairments are explored. Prevalence of cardiovascular dysfunction was found not to
improve over time after injury and it was highest in those with lesions above T5. The
second study showed that autonomic dysfunction contributes to overall CVD risk and
specifically to glucose intolerance, either directly or through an interaction with physical
activity levels. The data showed that waist circumference is the best marker for obesity
considering ability to detect adiposity and CVD risk, and practicality of use. A specific
cut-off for waist circumference was found to be lower compared to the general
recommendations. The final study showed increased values for the ECG markers Tpeak-
Tend variability, P-wave variability and QT variability index, only in those with
impairments to descending cardiac sympathetic pathways. The ECG characteristics may
be indicative of susceptibility to cardiac arrhythmia related to autonomic dysfunction.
Implications of these findings are that management of cardiovascular autonomic
dysfunction should remain a priority into the chronic phase of injury, not merely due the
direct impact on quality of life, but also due to its contribution to the elevated
cardiovascular disease risk after SCI.
Keywords: Spinal cord injury; autonomic nervous system; cardiovascular disease
risk; obesity; cardiac arrhythmia; autonomic dysfunction

iv
Acknowledgements
Four years of work went into my Ph.D. thesis, but I could not have done this all by
myself. Therefore, I would like to take this opportunity to thank those people who in one
way or another helped me to complete this journey.
First and foremost I would like to thank all the participants who volunteered their time
for the different studies. They are the ones who made this research possible. We had
some wonderful conversations during the two hour-long glucose tolerance tests; I
learned lots from each and every one of you!
Then my senior supervisor, Victoria: many thanks for the chance you gave me to start
my Ph.D. program in your lab, when I just moved to Vancouver. We worked closely
together both in the lab running the research studies and in teaching KIN 444. Thank
you for your guidance and support. I’m looking forward to continuing our collaboration
in the future.
My supervisory committee members, Scott Lear, Shubhayan Sanatani and Tom Claydon
are the next on my list to thank for their support. Your diverse backgrounds lead to
stimulating meetings about my project that gave me new inspiration to continue to
improve my research.
This journey would not have been the same without my lab mates! I’ve always been
happy to come into the lab, go for our daily coffee run and be able to pick each other’s
brains about all our projects. We had great fun at conferences and both inside and
outside lab (mostly during sporting adventures: skiing, cycling, climbing and scuba
diving). You’ve all become great friends!
Now I’d like to switch to Dutch to thank my family for their support. Dank jullie wel voor
alle steun voor mijn keuze naar Vancouver te gaan en het vertrouwen dat jullie in mij
hadden, ook al had ik dat soms niet. Ik vond het geweldig de afsluiting van deze 4 jaar
(mijn verdediging) samen met jullie te kunnen meemaken!
And last but not at all least: Mark, dank je wel lief, in de eerste plaats dat je me hebt
meegenomen naar Vancouver. We hebben hier samen en met lieve nieuwe vrienden een
geweldige tijd mogen beleven! Bedankt ook voor je steun en vertrouwen in mij en je
scherpe blik op mijn onderzoek, waardoor ik het nog beter kon maken. Succes nu met
jouw laatste loodjes en dan op naar een mooi nieuw avontuur samen!

v
Table of Contents
Approval .................................................................................................................. ii

Partial Copyright Licence .......................................................................................... iii

Abstract .................................................................................................................. iv

Acknowledgements ................................................................................................... v

Table of Contents .................................................................................................... vi

List of Tables ............................................................................................................ x

List of Figures .......................................................................................................... xi

List of Acronyms ...................................................................................................... xii

Chapter 1. Background ...................................................................................... 1

Spinal cord injury ...................................................................................................... 1

Incidence in Canada ......................................................................................... 2

Care and cure .................................................................................................. 3

Secondary complications of spinal cord injury ..................................................... 5

Autonomic function after spinal cord injury ................................................................. 7

Autonomic pathways ......................................................................................... 8

Cardiovascular autonomic pathways ......................................................... 10

Effects of spinal cord injury on cardiovascular autonomic pathways .................... 11

Acute effects on cardiovascular autonomic control .................................... 12

Arterial baroreflex and blood pressure control ..................................... 12

Adaptations to cardiovascular autonomic pathways ................................... 13

Consequences for cardiovascular function ........................................................ 15

Altered cardiac function .......................................................................... 15

Consequences of altered blood pressure control ....................................... 15

Low supine blood pressure ................................................................. 15

Orthostatic hypotension ..................................................................... 16

Autonomic dysreflexia ....................................................................... 18

Impaired blood pressure responses to exercise .................................... 21

Assessment of autonomic function after injury .................................................. 22

Plasma noradrenaline ............................................................................. 23

Muscle sympathetic nerve activity ............................................................ 23

Sympathetic skin responses ..................................................................... 24

Cutaneous vasomotor responses ............................................................. 24

Heart rate and blood pressure variability .................................................. 25

Relationship between cardiovascular autonomic dysfunction and cardiovascular
disease risk .................................................................................................... 26

Consequences of autonomic dysreflexia ........................................................... 26

Elevated risk of cardiac arrhythmias ................................................................. 27

Interaction effects between autonomic dysfunction and lifestyle ........................ 29

Obesity and obesity-related cardiovascular disease risk factors .................. 30

Outline of this thesis ............................................................................................... 32

vi
Chapter 2. Prevalence and progression of cardiovascular dysfunction
after spinal cord injury ............................................................... 33

Introduction ........................................................................................................... 33

Methods ................................................................................................................. 34

Participants .................................................................................................... 34

Design ........................................................................................................... 35

Cardiovascular parameters .............................................................................. 35

Personal and lesion characteristics ................................................................... 36

Statistical analyses .......................................................................................... 37

Results ................................................................................................................... 38

Participants .................................................................................................... 38

Time course and determinants of systolic and diastolic arterial pressure ............. 40

Time course and determinants of resting and peak heart rate ............................ 42

Prevalence of hypotension ............................................................................... 44

Prevalence of bradycardia, elevated heart rate, and tachycardia ........................ 44

Discussion .............................................................................................................. 46

Strengths and limitations ................................................................................. 50

Conclusion ............................................................................................................. 51

Chapter 3. Complex relationships between autonomic dysfunction,
lifestyle changes and cardiovascular disease risk ...................... 53

Introduction ........................................................................................................... 53

Methods ................................................................................................................. 55

Participants .................................................................................................... 55

Measurements of severity of injury .................................................................. 56

Standard neurological classification .......................................................... 56

Cardiovascular autonomic impairment ...................................................... 56

Plasma noradrenaline ........................................................................ 57

Systolic arterial pressure variability analysis ........................................ 57

Cardiovascular disease risk factors ................................................................... 58

Heart rate variability ............................................................................... 58

Blood lipid profiles, insulin and glucose levels ........................................... 58

Oral glucose tolerance ............................................................................ 59

Framingham 30-year risk for cardiovascular disease score ......................... 59

Physical activity level .............................................................................. 59

Body composition ................................................................................... 60

Statistical analyses .......................................................................................... 60

Results ................................................................................................................... 61

Participant characteristics ................................................................................ 61

Group differences in cardiovascular risk factors ................................................. 62

Multiple linear regression models for cardiovascular risk factors ......................... 64

Discussion .............................................................................................................. 67

Strengths and limitations ................................................................................. 70

Conclusion ............................................................................................................. 71

vii
Chapter 4. Waist circumference is the best index for obesity-related
cardiovascular disease risk in individuals with spinal cord
injury .......................................................................................... 72

Introduction ........................................................................................................... 72

Methods ................................................................................................................. 74

Participants .................................................................................................... 74

Anthropometric variables ................................................................................. 75

Body composition ........................................................................................... 75

Fasting plasma levels of lipids, glucose and insulin ............................................ 76

Oral glucose tolerance test .............................................................................. 76

Framingham 30-year risk for cardiovascular disease score ................................. 76

Statistical analyses .......................................................................................... 77

Results ................................................................................................................... 77

Participants .................................................................................................... 77

Anthropometric measures and body composition .............................................. 77

Anthropometric measures and cardiovascular disease risk factors ...................... 78

Anthropometric measures and the Framingham 30-year risk score ..................... 80

Discussion .............................................................................................................. 82

Conclusion ............................................................................................................. 86

Chapter 5. Electrocardiogram-based predictors for cardiac arrhythmia
are related to autonomic impairment after spinal cord
injury .......................................................................................... 87

Introduction ........................................................................................................... 87

Methods ................................................................................................................. 89

Participants .................................................................................................... 89

Measures of completeness of injury ................................................................. 89

Motor and sensory impairment ................................................................ 89

Autonomic impairment ............................................................................ 89

Sympathetic skin responses ............................................................... 90

Plasma noradrenaline levels ............................................................... 90

Low frequency power of systolic arterial pressure ................................ 91

Continuous electrocardiogram ......................................................................... 91

Electrocardiogram interval detection ........................................................ 91

Variability analyses ................................................................................. 92

12-lead electrocardiogram ............................................................................... 93

Statistics ........................................................................................................ 93

Results ................................................................................................................... 93

Participant characteristics ................................................................................ 94

Continuous electrocardiogram ......................................................................... 94

Electrocardiogram interval analyses ......................................................... 94

Variability analyses ................................................................................. 95

Correlations with autonomic impairment .................................................. 98

12-lead electrocardiogram ............................................................................... 98

Discussion ............................................................................................................ 100

Conclusion ........................................................................................................... 102

viii
Chapter 6. General discussion ....................................................................... 103

Prevalence and progression of cardiovascular autonomic dysfunction after spinal
cord injury ................................................................................................... 103

Role of autonomic impairment on cardiovascular disease risk ................................... 104

Obesity indices specific for individuals with spinal cord injury ................................... 106

Cardiac arrhythmias and autonomic function ........................................................... 107

Implications and future directions .......................................................................... 108

References ..................................................................................................... 110

Appendix. List of publications arising from this thesis ................................. 127

ix
List of Tables
Table 2.1.
 Participant characteristics ....................................................................... 38

Table 2.2.
 Cardiovascular variables at all test occasions according to lesion level ....... 39

Table 2.3.
  Blood pressure and heart rate regression analyses results ........................ 42

Table 2.4.
 Prevalence of hypotension, bradycardia, elevated heart rate and
tachycardia at all test occasions according to lesion level .......................... 45

Table 2.5.
  Prevalence of hypotension, bradycardia and elevated heart rate
regression analyses ................................................................................ 46

Table 3.1.
 Participant characteristics ....................................................................... 62

Table 3.2.
  Cardiovascular disease risk factor regression analyses results ................... 66

Table 4.1.
 Participant characteristics. ...................................................................... 78

Table 4.2.
 Correlations between anthropometric variables and individual risk
factors .................................................................................................. 80

Table 5.1.
 Participant characteristics. ...................................................................... 94

Table 5.2.
 ECG intervals: RRI, QT, QT , T -T and P-wave duration. ..................... 95

c peak end
Table 5.3.
 Variability parameters: T -T , QTVI and P-wave variability. .................. 98

peak end

x