Cardiovascular disease in cerebral palsy
Carotid-femoral pulse wave velocity
Carotid-femoral pulse wave velocity (cfPWV) is a regional
measure and the gold standard assessment of arterial stiffness
(15). cfPWV was determined from 20 continuous heart cycles
and arterial pressure waveforms at the areas of greatest pulsa-
tion from the common carotid and superficial femoral arteries,
and was calculated as follows:
cfPWV (m/s)=distance (m)/pulse transit time (s)
Distance was measured via the subtraction method as the
distance from the sternal notch to the femoral site minus the
distance from the sternal notch to the carotid site. An increase
in cfPWV is indicative of increased arterial stiffness and sub-
sequent risk for development of CVD.
Brachial artery flow-mediated dilation
Non-invasive assessment of endothelial function was measured
using the flow mediated dilation (FMD) technique performed
on the brachial artery. The FMD technique functions on the
premise that increases in shear rate (a surrogate for shear stress
in the absence of blood viscosity) cause vasodilation through an
upregulation and/or production of nitric oxide, which causes a
relaxation of the smooth muscle layer of the arterial wall, and
a subsequent increase in arterial diameter. Ultrasound was used
to acquire images of the brachial artery approximately 10 cm
proximal to the antecubital fossa. Absolute and relative FMD
values were calculated as reported previously (16). Reductions
in absolute and/or relative FMD values over time are indicative
of endothelial dysfunction and increased risk of CVD.
Statistical analysis
Statistical analyses were performed using STATA (version 13.1)
statistical software package. Descriptive summary statistics for
participants were calculated as means and SDs for continuous
variables and as percentages for categorical data (i.e. sex and
BMI categories).
To examine longitudinal changes in traditional and non-
traditional risk factors for CVD in individuals with CP, repea-
ted measures analysis of variance was performed. Dependent
variables of interest included waist circumference, SBP, cIMT,
carotid artery distensibility, cfPWV, and both absolute and
relative FMD, while time-point (baseline and follow-up) was
the independent variable. Difference in age (in months) between
baseline and follow-up assessments was entered as a covariate
to control for the differences in time between assessments for
participants.
To investigate the relationships between age and gross
motor function with longitudinal changes in traditional and
non-traditional risk factors for CVD, multiple linear regres-
sions were performed. Dependent variables consisted of waist
circumference, SBP, cIMT, carotid artery distensibility, cfPWV,
absolute and relative FMD. The regression models included
both age at baseline (as a continuous variable) and GMFCS
(dichotomous indicator variable; ambulatory (GMFCS I–II) vs
non-ambulatory (GMFCS III–V)) as independent variables. A
leverage vs residual squared plot was generated to determine
data points of high influence (i.e. outliers) followed by calcula-
ting Cook’s distance to confirm data points of high influence,
with those having a score ≥ 0.1 removed. Statistical significance
was set at an alpha criterion (0.05). A sample size calculation
was performed to determine the number of participants required
to examine longitudinal changes in CVD risk factors in indivi-
527
duals with CP with 80% power. Our sample was derived using
a one-tailed test and a medium effect size (0.5). Based on these
parameters, the target sample size would be 27.
RESULTS
Descriptive characteristics
Descriptive characteristics of the study participants are
presented in Table I. Twenty-eight of the 53 eligible
participants agreed to participate in the follow-up
assessments. The remaining 25 participants did not
participate for various reasons, some of which inclu-
ded: no longer living in Southwestern Ontario, not
willing to participate in follow-up research, or the
contact information that was on file was no longer ac-
curate. In addition, the time period between baseline
and follow-up assessment could have been up to 7
years for some participants, based on the time period
of the adolescent study (13); this probably contributed
to the reasons for non-participation in the follow-up
assessment, as other life demands could have taken
over. It was possible that individuals who participated
in the follow-up component of this study might be a
selection of more healthy participants compared with
those who did not participate; however, 2 sample t-tests
performed for age, and traditional and non-traditional
risk factors for CVD at baseline between participants
who participated in the follow-up and those who did
not revealed no significant between-sample differences
for all variables (i.e. p > 0.05). Our goal was to include
Table I. Descriptive characteristics and measures of risk factors
for cardiovascular disease (CVD) in individuals with cerebral palsy
(CP) at baseline and follow-up
Descriptive characteristics Baseline
(n = 28)
Age, years, mean (SD) [min–max] 31.2 (15.0) 35.1 (14.4) 4.0 (1.2)
Male,%
Traditional CVD risk factors
Follow-up
(n =28)
[10–75]
46.4
Δ (SD)
[16–78]
46.4
24.8 (8.2)
BMI, kg/m 2 , mean (SD)
Underweight (BMI < 18.5),%
28.6
Normal weight (BMI 18.5–24.9),% 35.7
Overweight (BMI 25–29.9),%
14.3
Obese (BMI ≥ 30),%
21.4
Waist circumference, cm, mean (SD) 81.0 (16.9)
SBP, mmHg, mean (SD)
120.3 (14.9)
DBP, mmHg, mean (SD)
71.0 (8.7)
MAP, mmHg, mean (SD)
90.1 (9.5)
Non-traditional CVD risk factors, mean (SD)
cfPWV, m/s
6.2 (1.4)
Absolute FMD, mm
0.31 (0.13)
Relative FMD,%
9.7 (4.7)
cIMT, mm
0.52 (0.17)
4.4E–3
Distensibility, mmHg –1
(2.2E–3)
26.1 (8.1)
17.9
32.1
21.4
28.6
84.0 (19.7)
118.9 (16.6)
69.5 (8.2)
88.2 (9.9) 1.3 (4.2)
6.9 (1.9)
0.22 (0.08)
7.5 (2.6)
0.67 (0.33)
3.4E–3
(1.7E–3) 0.4 (1.2)
–0.1 (0.1)
–2.4 (5.1)
0.2 (0.2)
–8.6E–4
(2.3E–3)
3.0 (7.4)
–1.4 (12.6)
–1.5 (8.2)
–1.8 (8.1)
BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood
pressure; MAP: mean arterial blood pressure; cfPWV: carotid femoral pulse
wave velocity; FMD: flow mediated dilation; cIMT: carotid artery intima media
thickness; SD: standard deviation.
J Rehabil Med 51, 2019