AUTONOMIC FUNCTION IS A HIGH PRIORITY 1 Bladder-Bowel-AD Tetraplegia Sexual function Walking Bladder-Bowel-AD Paraplegia Sexual function Walking 0 10 20 30 40 50 Percentage of respondents an ailment not to be treated Modified from Anderson 2004
CARDIOVASCULAR AUTONOMIC PATHWAYS 2 Parasympathetic: Unaffected by SCI RVLM Brainstem Vagus nerve X T1 - T5 Spinal cord T5 - L2 Sympathetic: Control of the heart at T1-T5 Baroreceptors Cardiac ganglion Paravertebral ganglion Prevertebral ganglion Control of the vasculature T1-L2 Splanchnic: T6-T10 Splanchnic vasculature Lower extremities Modified from Inskip 2009
CARDIOVASCULAR AUTONOMIC DYSFUNCTION 3 A Low resting blood pressure Orthostatic hypotension (OH) Autonomic dysreflexia (AD) Blood pressure (mm Hg) B Blood pressure (mm Hg) 150 100 50 0 200 150 100 Inhibition of Supine rest sympathetic Orthostatic challenge activity Recovery SCI above T6 50Full bladder or other sensory stimulus Decrease HR blockade for inhibition Afferent stimulus Sympathetic activity Baroreceptor sensing Hypertension Vasocontriction 0 Supine rest Bladder voiding " Recovery Modified from Blackmer, 2003
MANY CARDIOVASCULAR CONSEQUENCES OF INTERRUPTED SYMPATHETIC PATHWAYS 4 Atherosclerotic changes General fatigue Fainting Leptin function Exercise intolerance Insulin sensitivity Interrupted sympathetic pathways Hypertensive episodes Obesity Stroke Seizures Myocardial infarction Cardiac arrhythmias
ROLE IN CARDIOVASCULAR DISEASE RISK 5 Autonomic dysfunction Risk for Cardiovascular Disease Lifestyle Physical activity
OUTLINE 6 Prevalence of cardiovascular autonomic dysfunction Contribution of autonomic dysfunction to cardiovascular disease risk Waist circumference: the best marker for obesity after SCI ECG-based predictors for cardiac arrhythmias after SCI
PREVALENCE OF CARDIOVASCULAR AUTONOMIC DYSFUNCTION 7 Autonomic dysfunction only recently included in standard AIS assessment Changes over time not yet investigated Patient Name Examiner Name Date/Time of Exam Comments: STANDARD NEUROLOGICAL CLASSIFICATION OF SPINAL CORD INJURY (scoring on reverse side) (distal phalanx of middle finger) (little finger) REV 03/06
AIMS 8 I. to determine the prevalence of hypotension during and after inpatient rehabilitation II. to investigate the time course of blood pressure, resting and peak heart rate, during and after inpatient rehabilitation III. to evaluate the influence of personal and lesion characteristics on these cardiovascular variables
STUDY METHODS 9 197 participants with SCI Characteristics: Age & sex AIS score Time since injury Medical history Cardiovascular variables: Resting blood pressure Resting heart rate Peak heart rate (exercise) Hypotension Start of rehabilitation Discharge 2 years 3 months 1 year 5 years
PREVALENCE OF HYPOTENSION 10 Time course: no change Lesion level (cervical): Odds 4.2 times greater than low lesion group Odds 2.7 times greater than high thoracic group Age: Odds decreased with age, 0.75 per 10-years Sex: Men 2.2 times greater odds
Diastolic arterial pressure (mmhg) Systolic arterial pressure (mmhg) Peak Heart Rate (BPM) Resting Heart Rate (BPM) BLOOD PRESSURE AND HEART RATE CHANGES OVER TIME 11 A 130 Cervical High thoracic Low A 100 Cervical High thoracic Low 125 90 120 80 115 110 105 * * 70 60 100 Start 3 months Discharge 1 year 5 years 50 Start 3 months Discharge 1 year 5 years B 85 Cervical High thoracic Low B 170 Cervical High thoracic Low 80 75 70 160 150 140 65 130 60 120 55 Start 3 months Discharge 1 year 5 years 110 100 Start 3 months Discharge 1 year 5 years
CONCLUSIONS 12 Hypotension was common after spinal cord injury Impaired heart rate response to exercise Cardiovascular dysfunction mostly after cervical lesions No improvement over time
OUTLINE 13 Prevalence of cardiovascular autonomic dysfunction Contribution of autonomic dysfunction to cardiovascular disease risk Waist circumference: the best marker for obesity after SCI ECG-based predictors for cardiac arrhythmias after SCI
CONTRIBUTION OF AUTONOMIC DYSFUNCTION TO CARDIOVASCULAR DISEASE RISK 14 Autonomic dysfunction Lifestyle Physical activity Sympathetic control interrupted Leptin effects impaired Resting metabolic rate decreased Insulin receptor function Insulin sensitivity Low blood pressure Fatigue Barrier participation physical activity Deficient increase in heart rate Insufficient perfusion of muscles Poor exercise tolerance Autonomic dysfunction Risk for Cardiovascular Disease
AIMS 15 I. to determine the differences in cardiovascular disease risk between those with and without cardiovascular autonomic impairment after SCI, and able-bodied controls II. to investigate the contribution of autonomic impairments, physical activity levels, and their interaction to cardiovascular disease risk after SCI
STUDY METHODS: AUTONOMIC IMPAIRMENT 16 Plasma noradrenaline: cut-off < 0.56 nmol/l Low frequency systolic pressure variability: cut-off < 1.0 mmhg 2 Systolic arterial pressure (mmhg) 150 140 130 120 110 100 90 80 SCI C5 complete AB control 70 0 100 200 300 400 500 600 Heart beat number
STUDY METHODS: CVD RISK FACTORS AND PHYSICAL ACTIVITY LEVEL 17 Cardiovascular disease risk factors: Blood lipid profile Glucose tolerance Insulin Insulin resistance (HOMA) Glucose Framingham cardiovascular disease risk score: Age Sex Total cholesterol HDL cholesterol Smoking status Diabetes Anti-hypertensive treatment Systolic pressure Physical activity level: Physical Activity Scale for Individuals with Physical Disabilities
STUDY METHODS: MULTIPLE REGRESSION ANALYSES 18 Outcome measures: Framingham risk score Other risk factors Independent variables: Autonomic function (plasma NA) Physical activity level (PASIPD score) Interaction effect Confounder variables: Age Sex Waist circumference
MULTIPLE REGRESSION ANALYSES RESULTS 19 Framingham risk score 120 min glucose Insulin resistance Insulin Triglyceride HDL TC/HDL ratio Intercept -27.7 (10.4) -4.1 (1.0) 1.4 (0.2) 7.0 (0.7) -0.58 (0.6) 1.32 (0.4) -1.28 (1.5) Autonomic function Physical activity NE -0.37 (0.12) NE NE NE NE NE NE NE NE NE NE NE NE Interaction -0.17 (0.08) NE 0.02 (0.01) 0.1 (0.04) NE NE NE Age NE Sex Waist circumference NE 0.47 (0.12) NE NE NE 0.03 (0.01) -0.01 (0.005) 0.08 (0.02)
CONCLUSIONS 20 Autonomic impairment contributes to overall risk of cardiovascular disease Direct or indirect effects of autonomic impairment were shown for all glucose regulation variables No effect was found of autonomic impairment on lipid profile variables
OUTLINE 21 Prevalence of cardiovascular autonomic dysfunction Contribution of autonomic dysfunction to cardiovascular disease risk Waist circumference: the best marker for obesity after SCI ECG-based predictors for cardiac arrhythmias after SCI
22 WAIST CIRCUMFERENCE: THE BEST MARKER FOR OBESITY Problems with existing obesity indices: Challenging measurements General cut-off values Edwards et al. 2008
AIM 23 To identify the best marker for obesity-related CVD risk for those with SCI, considering: i. practicality of use ii. ability to detect adiposity and CVD risk
STUDY METHODS 24 27 participants with chronic SCI Anthropometric measures: Waist circumference (WC) BMI Waist-to-height ratio (WHtR) Neck circumference Waist-to-hip ratio (WHR) Body composition (DEXA): Fat percentage Abdominal fat percentage Framingham cardiovascular disease risk score
BMI, WC AND WHtR ARE CORRELATED WITH ABDOMINAL FAT PERCENTAGE A 50 B 50 25 40 40 Abdominal fat (%) C Abdominal fat (%) 30 20 10 0 10 15 20 25 30 35 40 BMI (kg/m2) 50 40 30 20 10 0 0.35 0.40 0.45 0.50 0.55 0.60 0.65 WHtR r = 0.751 p < 0.0001 r = 0.737 p < 0.0001 D Abdominal fat (%) Abdominal fat (%) 30 20 10 0 60 70 80 90 100 110 120 WC (cm) 50 40 30 20 10 0 0.6 0.7 0.8 0.9 1.0 1.1 1.2 WHR r = 0.590 p = 0.001 r = 0.346 p = 0.08 p
WC CORRELATED BEST WITH RISK SCORE 26 A 30 B 30 Framingham risk score 25 20 15 10 5 r = 0.655 p = 0.0007 Framingham risk score 25 20 15 10 5 r = 0.596 p = 0.003 C Sensitivity 0 1.00 0.90 0.80 0.70 0.60 0.50 0.40 0.30 0.20 0.10 0.00 70 80 90 100 110 WC WC AUC = 0.92 0.00 0.20 0.40 0.60 0.80 1.00 1-Specificity D Sensitivity 0 0.35 0.4 0.45 0.5 0.55 0.6 0.65 WHtR 1.00 0.90 0.80 0.70 0.60 0.50 0.40 0.30 0.20 0.10 0.00 WHtR AUC = 0.87 0.00 0.20 0.40 0.60 0.80 1.00 1-Specificity
CONCLUSIONS 27 Waist circumference is the best measure: simple and sensitive Optimal cut-off from this sample: 94 cm
GENERAL CONCLUSIONS 28 Cardiovascular autonomic dysfunction especially prevalent in those with high level lesions and it does not show improvement into the chronic stage Autonomic dysfunction plays a role in the increased risk of cardiovascular disease Important to quantify autonomic impairment as part of the standard assessment Waist circumference (with a specific cut off) is the best, simple index for obesity-related cardiovascular disease risk ECG parameters Tp-Te, QTVI and P-wave variability could be used to determine susceptibility to cardiac arrhythmias
THANK YOU SFU Cardiovascular Physiology Lab: Victoria Claydon Jessica Inskip Clare Protheroe Maureen McGrath Inderjeet Sahota Brett Shaw Mike Walsh