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Arterial stiffness in children with and without probable developmental coordination disorder
Research in Developmental Disabilities 59 (2016) 138–146
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Research in Developmental Disabilities
Arterial stiffness in children with and without probable developmental coordination disorder Nicole E. Philips a , Daniele Chirico a , John Cairney b , John Hay c , Brent E. Faught c , Deborah D. O’Leary c,d,∗ a
Faculty of Applied Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada Department of Psychiatry and Behavioural Neuroscience, Family Medicine, Kinesiology, and CanChild, Centre for Childhood Disability Research, McMaster University, Hamilton, ON L8P 0A1, Canada c Department of Health Sciences, Brock University, St. Catharines, ON, Canada d Brock-Niagara Centre for Health and Well-Being, Brock University, St. Catharines, ON L2S 3A1, Canada b
a r t i c l e
i n f o
Article history: Received 10 February 2016 Received in revised form 26 June 2016 Accepted 24 July 2016 Number of reviews : 2 Keywords: Arterial stiffness Children Common carotid artery Developmental coordination disorder Distensibility Pulse wave velocity
a b s t r a c t Background: Children with cardiovascular disease risk factors demonstrate adverse arterial alterations that are predictive of cardiovascular morbidity and mortality in adults. Children with developmental coordination disorder (DCD) are at cardiovascular risk as they are more likely to be obese and inactive. Aim: The purpose of this study was to assess arterial structure and function in children with and without probable DCD (p-DCD). Methods: A cross-sectional study of 33 children with p-DCD (22 male) and 53 without (30 male). The Movement Assessment Battery for Children was used to classify those with p-DCD. Adiposity was assessed using the BOD POD. Compliance, distensibility, and intimamedia thickness were measured at the common carotid artery (CCA). ECG R-wave-to-toe pulse wave velocity (PWV) was also measured. Results: Compared to controls, males with p-DCD had lower CCA distensibility (p = 0.034) and higher PWV (p = 0.001). No differences were evident in females. Body fat percent was a significant predictor of CCA distensibility and removed the effect of p-DCD on PWV in males. Conclusions: The present study demonstrates augmented arterial stiffness in males with p-DCD, likely attributed to body fat. These findings underscore the importance of targeted interventions in children with p-DCD, specifically males, in order to prevent future cardiovascular risk. © 2016 Elsevier Ltd. All rights reserved.
What this paper adds Children with cardiovascular disease risk factors demonstrate adverse arterial alterations that are predictive of cardiovascular morbidity and mortality in adults. Children with developmental coordination disorder (DCD) are less likely to participate in physical activity and are more likely to be obese than their peers. Consequently, these children are at an increased risk of early arterial changes. However, no study has examined the link between DCD and arterial health in children. As a result, this study was the first to show that males with probable DCD (p-DCD) exhibit increased arterial stiffness
∗ Corresponding author at: Department of Health Sciences, Brock-Niagara Centre for Health and Well-Being, 500 Glenridge Ave, St. Catharines, Ontario, L2S 3A1, Canada. E-mail addresses: [email protected] (N.E. Philips), [email protected] (D. Chirico), [email protected] (J. Cairney), [email protected] (J. Hay), [email protected] (B.E. Faught), [email protected] (D.D. O’Leary). http://dx.doi.org/10.1016/j.ridd.2016.07.011 0891-4222/© 2016 Elsevier Ltd. All rights reserved.
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compared to controls; a finding that was attributed to excess adiposity in this population. In addition, this is the first study to show sex differences with respect to arterial health in children with p-DCD. No differences were seen in arterial health between females with and without p-DCD. As a result, males with p-DCD are at an increased risk for cardiovascular complications later in life. The results of this study highlight the importance of targeted interventions in children with p-DCD, specifically males with excess adiposity, in order to prevent future cardiovascular risk. 1. Introduction Developmental coordination disorder (DCD) is a neurological disorder with a global prevalence of approximately 1.8% of children, and is reported more often in boys (Lingam, Hunt, Golding, Jongmans, & Emond, 2009). Children with DCD exhibit poor motor skills and coordination, which adversely affects their participation in physical activity (Batey et al., 2014). Children with DCD also exhibit a greater prevalence of cardiovascular disease risk factors. Substantial research has illustrated that compared to their typically developing peers, children with DCD have greater body mass index (BMI) and waist circumference (Joshi et al., 2015), higher percent body fat (PBF) (Cairney, Hay, Veldhuizen, & Faught, 2011), greater prevalence of overweight/obesity (Cairney, Hay, Faught, & Hawes, 2005), lower cardiorespiratory fitness (Wu, Lin, Li, Tsai, & Cairney, 2010), and decreased physical fitness (Schott, Alof, Hultsch, & Meermann, 2007). Likewise, we have demonstrated that children with probable DCD (p-DCD), in comparison to their typically developing peers, have reduced autonomic regulation of blood pressure (BP) and atypical left ventricular structure and function, two supplementary markers of cardiovascular health (Chirico et al., 2011; Coverdale et al., 2012). Consequently, children with DCD are at an increased risk of developing cardiovascular disease. Noninvasive measures of arterial stiffness, such as reduced arterial distensibility and compliance, and increased pulsewave velocity (PWV) and arterial thickness (i.e., intima-media thickness [IMT]) are established predictors of cardiovascular morbidity and mortality in adults (Hodis et al., 1998; van Sloten et al., 2014; Vlachopoulos, Aznaouridis, & Stefanadis, 2010). These measures also demonstrate utility in identifying adverse arterial alterations in children who are less physically active, hypertensive or pre-hypertensive, and overweight. (Banach et al., 2010; Edwards et al., 2012; Urbina et al., 2011). Early arterial alterations in childhood may translate into accelerated cardiovascular risk in adulthood. Therefore, identification of children with heightened cardiovascular risk is critical. However, there are no studies evaluating arterial stiffness in children with DCD to our knowledge. The purpose of this investigation was to determine whether children diagnosed with p-DCD demonstrate increased arterial stiffness and thickness as measured by PWV, compliance, distensibility, and IMT of the common carotid artery (CCA) compared to age, sex and school matched controls. 2. Methods 2.1. Study population The sample was drawn from a larger population-based study known as the Physical Health Activity Study Team (PHAST) study, the details of which have been described previously (Cairney, Hay, Veldhuizen, & Faught, 2010). The Brock University Research Ethics Board and the District School Board of Niagara approved this study and consent/assent was provided by all parents/participants. There were 198 participants identified with p-DCD, scoring below the 10th percentile on the BruininksOseretsky Test of Motor Proficiency-Short Form (BOTMP-SF) during a health assessment in school. These individuals were invited by telephone to participate in annual lab-based assessments for three consecutive years, and a total of 63 agreed to participate. Healthy controls (63) were selected randomly from consenting students who scored above the 10th percentile on the BOTMP-SF and were matched for sex, school, and age within 6-months. All participants assessed in the lab were administered the Movement Assessment Battery for Children-2 (M-ABC2) to verify clinically significant motor coordination difficulties. The analyses reported are data collected from year three, and only includes those who completed all three years of the lab assessment. A total of 40 participants declined the invitation to return for the second and third years of assessment, resulting in a final sample size of 86 participants, of which, 33 had M-ABC2 scores ≤16th (p-DCD) and 53 controls scoring above the 16th percentile. 2.2. Experimental procedure Participants were scheduled for an appointment at the Applied Physiology Laboratories at Brock University. They were instructed to avoid strenuous physical activity/exercise twenty-four hours prior, as well as caffeine and food intake at least four hours prior to their assessment. Standing height, body mass and adiposity were assessed. Participants then entered the Human Hemodynamic Laboratory for cardiovascular measures. Once in the lab, participants were asked to lie supine for a period of 15 min to allow BP and heart rate (HR) to reach resting levels. Following this rest period, three manual BP measurements were taken with each measure separated by one minute. Participants then underwent five minutes of beat-by-beat HR, BP and PWV data collection. At the end of five minutes, right CCA ultrasound images were taken. Once data collection was complete, another three manual BP measurements were taken to ensure participants were still at rest.
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Upon completion of the cardiovascular assessment, participants were administered the M-ABC2 by a trained occupational therapist, followed by the completion of a peak oxygen uptake test (peak VO2 ). Finally, pubertal staging was completed seven to eight days following laboratory testing. 2.3. Measures 2.3.1. Anthropometrics Body mass index (BMI) was calculated using standing height and body mass (kg/m2 ). Standing height (cm) was measured using a stadiometer (Stat 7X, Ellard Instrumentation 50 Ltd Monroe, WA, USA) with the participants’ shoes removed and recorded to the nearest 0.1 cm. Body mass (kg) was measured using a digital scale (BWB-800S, Tanita Digital Scale, Tokyo, Japan) and recorded to the nearest 0.1 kg. Fat mass (FM), fat-free mass (FFM), and PBF were determined using whole body air-displacement plethysmography with the BOD POD (Life Measurement, Inc, Concord, CA), which has been explained in detail previously (Chirico et al., 2011). 2.3.2. Blood pressure and heart rate Brachial BP was taken using a standard inflatable cuff and sphygmomanometer placed on the right arm at heart level while participants rested in the supine position. Three measures were taken and averaged to provide systolic BP (SBP) and diastolic BP (DBP) values. In addition, five minutes of continuous beat-by-beat non-invasive BP was collected from the left middle finger using photoplethysmography (Nexfin, BMEYE, Amsterdam, The Netherlands). Since finger BP differs marginally from brachial BP, beat-by-beat BP was adjusted to the manual brachial BP to ensure accuracy (Imholz, Settels, van der Meiracker, Wesseling, & Wieling, 1990). A one-minute average of SBP, DBP and mean arterial pressure (MAP = 1/3·SBP + 2/3·DBP) was determined. Likewise, HR was collected using a standard one-lead ECG and a one-minute R-R interval (RRI) average was used to calculate HR by dividing the average RRI (sec) into 60. 2.3.3. Vascular measures Central compliance and distensibility were measured at the right CCA using non-invasive Echo-Doppler ultrasound (Vivid I, GE Medical Systems, Horton, Norway). Images were taken while participants were supine using an 8 MHz linear array transducer approximately 1–2 cm proximal to the carotid artery bifurcation. Three images consisting of five beat-by-beat diameter changes were taken for each subject using high resolution B-mode. The two best images were selected, based on image quality, to measure CCA compliance and distensibility. The best three beats from each image were chosen and diameters corresponding to systole and diastole were measured using computer automated edge detection software (Artery Measurement System II, Image and Data Analysis). Lumen diameter (LD) was measured from the leading edge of the near wall intima to the leading edge of the far wall intima. Intima-media thickness (IMT) was measured at end-diastole at the far wall for the same cardiac cycles as diameters. Pulsatile cross sectional area (CSA; r2 , where r = diameter/2) and corresponding finger pressures were used to determine CCA compliance and distensibility using the following equations: Compliance = (sCSA − dCSA)/(Ps − Pd ) and Distensibility = ((sCSA − dCSA)/dCSA)/(Ps − Pd ) where sCSA and dCSA are systolic and diastolic cross-sectional areas and Ps and Pd are systolic and diastolic finger pressures, respectively. Pulse wave velocity (PWV) was measured noninvasively using ECG and the pulse wave at the left second toe (Nellcor N-200 Tyco Healthcare Group LP, Pleasanton, Calif., USA); a similar method has been used in children (Currie, Proudfoot, Timmons, & MacDonald, 2010). The time delay between the R peak on the ECG to the beginning of the upstroke of the pressure waveform was used to calculate pulse transit time (s), averaged over ten consecutive beats. Distance (m) was measured from the sternal notch to the left middle toe. PWV was calculated using the following equation: PWV(m/s) = (Distance)/(TransitTime)
2.3.4. Assessment of motor coordination Motor coordination of all participants was assessed each year by a trained occupational therapist using the M-ABC2. As children may perform better or worse depending on the conditions or the day, an average score for the 3 years was used to accurately identify children with motor impairments. Scores were converted into percentiles and those with averages below the 16th percentile were identified as p-DCD. Probable cases of DCD were identified as p-DCD due to the fact that information about criterion B from the DSM-V was missing (American Psychiatric Association, 2013). In addition, the Kaufman Brief Intelligence Test was administered by the occupational therapist to verify participants’ intellectual ability and to satisfy criterion D from the DSM-V (American Psychiatric Association, 2013).
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2.3.5. Aerobic fitness A peak VO2 test using a programmed cycle ergometer (Excalibur Sport V2, Lode BV, Groningen, The Netherlands) was used to measure peak aerobic power. This procedure consists of a continuous and incremental exercise protocol, which has been previously described (Silman, Cairney, Hay, Klentrou, & Faught, 2011). Criteria used to assess achievement of peak aerobic power required at least two of the following: (1) a respiratory gas exchange ratio of at least 1.0; (2) HR was greater than 85% of theoretical maximal level for age (220-age); and/or (3) physical signs of intense effort (facial flushing, or difficulty maintaining speed cycle) (Armstrong and Van Mechelem, 2008; Dencker et al., 2007). For between group comparisons, peak VO2 was adjusted for FFM (peak VO2FFM ), which has been shown to be the most appropriate method for normalizing for body size (Dencker et al., 2007). 2.3.6. Maturation Pubertal maturation was self-reported using pictures of the Sexual Maturation Scale for pubic hair and genitalia development by Tanner and taken from Taylor et al. (2001). Each subject completed the self-assessment at home seven to eight days following laboratory testing, in the presence of his or her parent(s), and placed it in an envelope to maintain confidentiality. Three male controls did not complete the Tanner scale. 2.4. Statistical analysis Statistical analyses were carried out using SPSS software version 20.0 for Windows (IBM SPSS Statistics 20) and the level of significance was set at p ≤ 0.05. Multivariable linear regressions were performed to determine whether the effect of p-DCD on PWV, IMT, compliance and distensibility varied by sex (a sex by p-DCD interaction). Due to a significant sex by p-DCD interaction for PWV and distensibility (p < 0.05), all descriptive statistics for participants with p-DCD (average M-ABC2 over 3 years < 16th percentile) and controls (average M-ABC2 over 3 years ≥ 16th percentile) are reported separately for males and females. Independent t-tests and chi-square tests were used to examine differences in experimental measures between children with and without p-DCD in both populations. Results are expressed as mean (SD). To address the study’s intended purpose, two separate multivariable linear regressions were performed in males to examine the effect of p-DCD on PWV and p-DCD on distensibility. Relevant variables differing between groups were controlled for (i.e. HR, VO2FFM and PBF) and values are presented as regression coefficients. All variables were checked for normality using the Shapiro-Wilk test. Although several variables were not normally distributed, after performing Mann Whitney U tests for these variables the results remained unchanged. Given that the results do not change with non-parametric analyses, and the sample size is large (>30), we continue to report parametric analyses. 3. Results 3.1. Sample characteristics Table 1 presents group differences separated by sex for demographic, anthropometric, and cardiovascular variables. The p-DCD group had lower M-ABC2 scores compared to controls, while age and K-BIT were not different between groups for males or females. For anthropometric measures, body mass, BMI, PBF and FM were higher in the p-DCD group (p < 0.01) in males. In females, only PBF was significantly greater in the p-DCD group (p = 0.028). For cardiovascular measures, HR was higher (p = 0.014) and peak VO2FFM was lower (p = 0.008) in males with p-DCD compared to controls. Peak VO2 (p = 0.003) and peak VO2FFM (p = 0.030) were lower in females with p-DCD compared to controls. Finally, sexual maturation was not different between groups for males or females. 3.2. Arterial characteristics Characteristics of arterial structure and function are shown in Table 2 and are presented separately by group (p-DCD versus control) and sex. Due to inadequate image quality and missing data: 7 male and 4 female participants were excluded from analysis of compliance, distensibility and IMT, and 6 male and 6 female participants were excluded from PWV analysis. Diastolic diameter (p = 0.026) and PWV (p = 0.001) were greater, while distensibility (p = 0.034) was lower in the p-DCD group compared to controls in males. There were no group differences in arterial structure and function in females. Sex differences in distensibility and PWV were confirmed using multivariate linear regression. PWV and distensibility were analyzed based on two models; 1) effect of p-DCD, 2) p-DCD adding sex and the sex/p-DCD interaction (Table 3). In model one, examining p-DCD and PWV, the main effect of p-DCD was positive and significant (p = 0.016), accounting for 6.5% of the variability in PWV (R2 adjusted = 0.065). When sex and the sex/p-DCD interaction term were entered in model two, the interaction term was significant (p = 0.010), accounting for ∼16% of the variability (R2 adjusted = 0.156). Furthermore, in the first model examining p-DCD and distensibility, the main effect of p-DCD was not significant (p = 0.389). However, when sex and the sex/p-DCD interaction were added in model two, the interaction term was significant (p = 0.013), accounting for 7% of the variability (R2 adjusted = 0.071). These interactions are illustrated in Fig. 1. Since the effect of p-DCD was only found to be a significant predictor of PWV and distensibility in males, further analysis focused only on this population. Multivariable regression analyses consisting of four models were implemented to test
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Table 1 Demographic and cardiovascular characteristics for male and female children with p-DCD and controls. Male
Female
p-DCD
Control
p-value
p-DCD
Control
p-value
Demography Age (y:mo) M-ABC2 (percentile) K-BIT
n = 22 14:10 (0:6) 7.0 (4.6) 94 (11.6)
n = 30 14:8 (0:5) 48.7 (14.8) 99 (10.8)
0.357 0.001 0.146
n = 11 14:6 (0:5) 7.5 (3.8) 88 (16.2)
n = 23 14:7 (0:6) 48.0 (20.1) 96 (7.9)
0.172 0.000 0.119
Anthropometry Height (cm) Body Mass (kg) BMI (kg/m2 ) PBF FM (kg) FFM (kg)
172.4 (6.5) 78.3 (24.4) 26.2 (7.2) 27.8 (11.5) 23.6 (15.5) 54.7 (11.9)
172.8 (5.3) 59.7 (8.2) 20.1 (2.5) 12.5 (6.8) 7.7 (5.1) 53.5 (9.0)
0.821 0.002 0.001 0.000 0.000 0.685
161.6 (6.7) 63.8 (15.6) 24.4 (4.6) 32.1 (9.7) 21.5 (10.3) 42.3 (6.5)
163.9 (5.7) 61.1 (11.9) 22.8 (4.2) 25.3 (7.1) 16.1 (7.4) 45.0 (6.2)
0.303 0.584 0.331 0.028 0.086 0.237
Cardiovascular Variables SBP (mmHg) DBP (mmHg) MAP (mmHg) HR (bpm) Peak VO2 (L/min) Peak VO2 (mL/kgFFM /min)
113 (13) 64 (10) 80 (10) 74.9 (13.1) 3.0 (0.7) 54.7 (7.7)
108 (11) 60 (11) 76 (10) 67.0 (9.3) 3.3 (0.5) 61.9 (10.3)
0.149 0.192 0.129 0.014 0.089 0.008
105 (10) 64 (10) 77 (9) 73.6 (8.6) 2.0 (0.3) 47.8 (7.1)
111 (10) 68 (12) 82 (10) 71.1 (8.8) 2.4 (0.5) 53.9 (7.4)
0.097 0.223 0.142 0.444 0.003 0.030
Mean (SD) Independent-samples t-test. p-DCD = probable Developmental Coordination Disorder, y = years, mo = months, M-ABC2 = Movement Assessment Battery for Children 2nd edition, K-BIT = Kaufmann Brief Intelligence Test, BMI = Body Mass Index, PBF = Percent Body Fat, FM = Fat Mass, FFM = Fat Free Mass, SBP = Systolic Blood Pressure, DBP = Diastolic Blood Pressure, MAP = Mean Arterial Pressure, HR = Heart Rate, bpm = beats per minute, VO2 = Peak Aerobic Fitness. Table 2 Arterial measures in children with p-DCD and controls by sex. Male
Female
p-DCD
Control
p-value
p-DCD
Control
p-value
Arterial Diameters Systolic (mm) Diastolic (mm) Difference (mm)
n = 18 6.55 (0.41) 5.64 (0.45) 0.87 (0.22)
n = 27 6.29 (0.57) 5.31 (0.48) 0.97 (0.23)
0.103 0.026 0.171
n = 10 6.06 (0.50) 5.23 (0.40) 0.86 (0.18)
n = 20 6.15 (0.47) 5.36 (0.40) 0.77 (0.17)
0.608 0.379 0.260
Arterial Stiffness PP (mmHg) PWV (m/s) Compliance (mm2 /mmHg) Distensibility (mmHg−1 × 10−2 )
52.2 (13.5) 4.1 (0.3) (n = 20) 0.17 (0.03) 0.70 (0.17)
50.5 (9.2) 3.8 (0.2) (n = 26) 0.18 (0.05) 0.82 (0.19)
0.619 0.001 0.506 0.034
44.2 (7.2) 3.8 (0.4) (n = 9) 0.17 (0.05) 0.79 (0.14)
46.3 (7.3) 3.8 (0.3) (n = 19) 0.16 (0.05) 0.70 (0.15)
0.464 0.523 0.492 0.123
Arterial Thickness IMT (mm)
0.39 (0.04)
0.40 (0.05)
0.483
0.39 (0.03)
0.39 (0.05)
0.981
Mean (SD) Independent-samples t-test. p-DCD = probable Developmental Coordination Disorder, PP = Pulse Pressure, PWV = Pulse Wave Velocity, IMT = Intima-Media Thickness.
A
B 0.82
4.2
PWV (m/s)
4 3.9
Male Female
3.8 3.7 3.6
Distensibility (mmHg -1 x 10 -2)
0.8
4.1
0.78 0.76 0.74
Male
0.72
Female
0.7 0.68 0.66 0.64
3.5 p-DCD
Control
p-DCD
Control
Fig. 1. Interaction between sex and probable Developmental Coordination Disorder (p-DCD) with respect to a) pulse wave velocity (PWV) (p = 0.010) and b) distensibility (p = 0.013).
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Table 3 Multivariable linear regression of p-DCD on PWV and distensibility.
PWV Model 1 Constant p-DCD Model 2 Constant p-DCD Sex Sex*p-DCD Distensibility Model 1 Constant p-DCD Model 2 Constant p-DCD Sex Sex*p-DCD
R
R2
R2 adjusted
(n = 74) 0.279
0.078
0.065
0.436
0.190
(n = 75) 0.101
Bstandardized
p-value
3.828 0.169
0.280
0.000 0.016
3.819 0.284 0.021 −0.361
0.469 0.034 −0.400
0.000 0.001 0.803 0.010
0.008 0.000
−0.101
0.000 0.389
0.008 −0.001 −0.001 0.002
−0.334 −0.344 0.414
0.000 0.022 0.017 0.013
0.156
−0.003
0.010
0.329
bunstandardized
0.108
0.071
PWV = pulse wave velocity, p-DCD = probable Developmental Coordination Disorder. Table 4 Multivariable linear regression of p-DCD on PWV and distensibility in males. R2
R2 adjusted
bunstandardized
Bstandardized
p-value
PWV (n = 46) Model 1 Model 2 Model 3 Model 4
0.236 0.257 0.282 0.293
0.218 0.223 0.231 0.224
0.284 0.249 0.226 0.171
0.485 0.426 0.387 0.293
0.001 0.004 0.011 0.124
Distensibility (n = 45) Model 1 Model 2 Model 3 Model 4
0.100 0.131 0.138 0.246
0.079 0.089 0.075 0.171
−0.001 −0.001 −0.001 0.0001
−0.316 −0.266 −0.236 0.021
0.034 0.082 0.146 0.910
Model 1–unadjusted. Model 2–adjusted for heart rate. Model 3–adjusted for heart rate and peak VO2FFM . Model 4–adjusted for heart rate, peak VO2FFM , and body fat percent.
the independent effect of p-DCD on PWV and distensibility in males, while adjusting for covariates (Table 4). For PWV, in models 1–3, it was shown that p-DCD was an independent predictor of PWV. However, when adding PBF (model 4), p-DCD was no longer an independent predictor. None of the covariates were significant predictors of PWV. For distensibility, after controlling for HR (model 2), p-DCD was no longer a significant predictor, which remained true for models 3 and 4 as well. Only PBF (model 4) was a significant predictor of distensibility (p = 0.022). 4. Discussion The purpose of this study was to determine whether children with p-DCD demonstrate greater arterial stiffness than typically developing peers. The primary finding was a sex/p-DCD interaction effect on PWV and distensibility; males with pDCD had faster PWV and reduced distensibility compared to controls, while no difference was seen in females. The augmented PWV and attenuated distensibility in p-DCD males may be attributed to a higher PBF, as it removed the main effect on PWV and was a significant predictor of distensibility. In addition, it was found that males with p-DCD exhibited significant differences in HR and peak VO2FFM , while females with p-DCD demonstrated significant differences in peak VO2 and VO2FFM . Based on current literature, possible explanations to the sex-dependent increase in arterial stiffness associated with pDCD include overweight/obesity, and physical inactivity (Edwards et al., 2012; Tounian et al., 2001). In a study examining the effect of physical activity in children with p-DCD, Batey et al. (2014) determined that physical activity is reduced in males with DCD, but not in females, compared to controls. These authors found that males and females with p-DCD, and females without p-DCD demonstrated similar time spent in moderate to vigorous physical activity, while males without p-DCD spent a significantly greater amount of time in moderate to vigorous physical activity. Activity levels in males are therefore more susceptible to p-DCD status and likely contribute to differences in arterial stiffness in the present study. A recent study by Joshi et al. (2015) examined the long-term impact of p-DCD on BMI and waist circumference over a five-year period. It was found that BMI and waist circumference were elevated in those with p-DCD, and these differences
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increased over time in males, but not females. Although physical activity did not affect this relationship, it was negatively correlated with BMI and waist circumference. As well, it has been demonstrated that PBF is greater in children with DCD (Cairney et al., 2011), and the prevalence of overweight/obesity is greater in males with p-DCD compared to controls, but not females (Cairney et al., 2005). Consistent with these findings, male children with p-DCD in the present study have increased fat mass and PBF compared to controls (Cairney et al., 2011). Taken together, previous findings demonstrate sex-specific effects of p-DCD on health outcomes and the current study further extends these differences to increased arterial stiffness in males with p-DCD, but not females when compared to healthy peers. The measure of PWV in the present study differs slightly from the gold-standard. Typically, PWV is measured from the carotid and femoral arteries whereas we measured PWV from the peak of the R-wave to the toe. A similar method of measuring PWV has shown to be feasible and reliable in children (Currie et al., 2010) and provides a practical option in our population. This method is not only less time consuming, but is also less dependent on operator skill and participant compliance and may be useful for large-scale studies of arterial health in child populations, such as this one. In comparing our values to Currie et al. (2010), they are slightly higher (3.8 and 4.1 m/s versus 3.5 ± 0.3 m/s). This is to be expected as Currie and colleagues examined pre-school aged children, whereas the present study investigated children with an average age of 14 years. PWV has been shown to increase with age (Voges et al., 2012), as well as demonstrate a maturation/sex interaction (Ahimastos, Formosa, Dart, & Kingwell, 2003). However, these factors are not believed to have impacted the results as groups were matched for age and sex, and maturation was not significantly different between p-DCD and controls. There was no difference in CCA compliance between groups in the present study. Compliance is a size dependent measure of arterial stiffness and differences between groups may have been masked by the fact that males with p-DCD had higher diastolic diameters compared to controls. Nevertheless, CCA distensibility was significantly lower in males with p-DCD compared to controls. When controlling for covariates this difference was no longer significant, with PBF being the only significant predictor of distensibility. These findings are similar to that of Banach et al. (2010), and Tounian et al. (2001) who found an increase in diastolic diameter and a decrease in CCA distensibility in overweight/obese children. As well, we have demonstrated that CCA distensibility negatively correlates with PBF and positively correlates with peak VO2FFM (Banach et al., 2010). Therefore, the finding of diminished CCA distensibility in males in the present study is supported by previous research suggesting that body fat and aerobic fitness are important determinants of distensibility. In contrast to arterial stiffness measures, IMT was not different between p-DCD and controls. Evidence suggests that IMT can be augmented in children with obesity and high BP (Litwin et al., 2004, 2006; Urbina et al., 2011). However, it is critical to highlight that the average BMI and BP values in the present study are considerably lower than studies assessing the effect of obesity and high BP on IMT. For example, Meyer, Kundt, Steiner, Schuff-Werner, and Kienast, 2006 examined obesity and IMT in children (aged 9–16 years) whose mean BMI was 30.6 kg/m2 compared to 20.4 kg/m2 in controls. In contrast, p-DCD children in the current study had a mean BMI of 25.6 kg/m2 , while controls had a mean BMI of 21.3 kg/m2 . Likewise, studies assessing the effect of elevated BP on IMT in children have compared clinically hypertensive children to those that are normotensive (Litwin et al., 2004, 2006; Urbina et al., 2011). In contrast, BP values in the present study for both groups were within the normal range. However, in support of our findings, a study by Aggoun et al. (2008) reported that arterial stiffness was elevated in obese children aged 8.8 years old, compared to controls; although, IMT was not different. This suggests that alterations in arterial stiffness (PWV and distensibility) may precede changes in arterial structure (IMT). Support for the importance of early cardiovascular modification on future health is emphasized in literature demonstrating small differences in cardiovascular disease risk in childhood can predict risk of atherosclerotic development in adulthood (Ferreira, van de Laar, Prins, Twisk, & Stehouwer, 2012). For example, in the Amsterdam Growth and Health Longitudinal Study, a 24-year follow-up revealed that individuals in the lowest tertile of carotid distensibility (greater stiffness) at age 36 demonstrated elevated BMI at 15 years old, compared to those in the highest tertile (Ferreira et al., 2012). These findings underscore the importance of childhood as a critical time period in which early alterations can result in accelerated future risk. Likewise, small differences in PWV and distensibility are perceived to be important as minimal increases in PWV (1 m/s) and decreases in distensibility (1 SD) have been shown to significantly increase risk of cardiovascular and all-cause mortality in adults (van Sloten et al., 2014; Vlachopoulos, Aznaouridis, & Stefanadis, 2010). Although males with p-DCD demonstrate PWV and distensibility values within the normal range, the augmented arterial stiffness remains concerning as it is likely to predict increased risk in adulthood. These results emphasize the importance of targeting interventions at a young age in children with p-DCD as to prevent an augmented risk of cardiovascular disease in adulthood.
4.1. Limitations First, we were unable to confirm whether the motor impairments experienced by children with p-DCD significantly interfered with activities of daily living and/or academic performance. As a result, we were unable to meet the full criteria of the DSM-V and therefore identified children as having p-DCD. Second, since this is an ancillary cross-sectional design within a larger longitudinal study, we cannot make causal links between p-DCD and cardiovascular risk. Tracking arterial changes over time in children with p-DCD will provide a better understanding of how arterial structure and function are altered in this population. Lastly, power to detect a difference in distensibility was low for females. Therefore, we cannot say with certainty that arterial changes within this population were absent. However, this is not believed to have influenced
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the interpretation of the results as it was shown that females with p-DCD had greater (non-significant) distensibility than TD controls, while PWV was identical. 5. Conclusion This was the first study to examine arterial health in children with p-DCD. Males with p-DCD exhibited augmented arterial stiffness via faster PWV and diminished carotid distensibility compared to controls, while females did not. The increased arterial stiffness in males with p-DCD can be attributed to excess adiposity. As a result, it is apparent that sex differences exist with respect to arterial health within this population and that males with p-DCD may be more likely to develop arterial stiffness later in life. The results of this study highlight the necessity of targeted interventions in children with p-DCD, specifically males with excess adiposity, in order to prevent future cardiovascular risk. Acknowledgements This study was funded by the Canadian Institutes of Health Research (grant no. 66959). John Cairney is supported by an endowed professorship from the Department of Family Medicine at McMaster University. References Aggoun, Y., Farpour-Lambert, N. J., Marchand, L. M., Golay, E., Maggio, A. B., & Beghetti, M. (2008). Impaired endothelial and smooth muscle functions and arterial stiffness appear before puberty in obese children and are associated with elevated ambulatory blood pressure. European Heart Journal, 29, 792–799. Ahimastos, A. A., Formosa, M., Dart, A. M., & Kingwell, B. A. (2003). Gender differences in large artery stiffness pre- and post puberty. The Journal of Clincal Endocrinology and Metabolism, 88, 5375–5380. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC, USA: American Psychiatric Association Press. Armstrong, N., & Van Mechelem, W. (2008). Aerobic fitness. Paediatric exercise science and medicine. New York, NY: Oxford University Press. Banach, A. M., Peralta-Huertas, J., Livingstone, K., Petrella, N., Klentrou, P., Faught, B., et al. (2010). Arterial distensibility is reduced in overweight pre- and early pubescent children. European Journal of Pediatrics, 169, 695–703. Batey, C. A., Missiuna, C. A., Timmons, B. W., Hay, J. A., Faught, B. E., & Cairney, J. (2014). Self-efficacy toward physical activity and the physical activity behavior of children with and without Developmental Coordination Disorder. Human Movement Science, 36, 258–271. Cairney, J., Hay, J. A., Faught, B. E., & Hawes, R. (2005). Developmental coordination disorder and overweight and obesity in children aged 9–14 y. International Journal of Obesity, 29, 369–372. Cairney, J., Hay, J., Veldhuizen, S., & Faught, B. E. (2010). Trajectories of cardiorespiratory fitness in children with and without developmental coordination disorder: A longitudinal analysis. British Journal of Sports Medicine, 45, 1196–1201. Cairney, J., Hay, J., Veldhuizen, S., & Faught, B. (2011). Assessment of body composition using whole body air-displacement plethysmography in children with and without developmental coordination disorder. Research in Developmental Disabilities, 32, 830–835. Chirico, D., O’Leary, D., Cairney, J., Klentrou, P., Haluka, K., Hay, J., et al. (2011). Left ventricular structure and function in children with and without developmental coordination disorder. Research in Developmental Disabilities, 32, 115–123. Coverdale, N. S., O’Leary, D. D., Faught, B. E., Chirico, D., Hay, J., & Cairney, J. (2012). Baroreflex sensitivity is reduced in adolescents with probable developmental coordination disorder. Research in Developmental Disabilities, 33, 251–257. Currie, K. D., Proudfoot, N. A., Timmons, B. W., & MacDonald, M. J. (2010). Noninvasive measures of vascular health are reliable in preschool-aged children. Applied Physiology Nutrition and Metabolism, 35, 512–517. Dencker, M., Thorsson, O., Karlsson, M. K., Linden, C., Eiberg, S., Wollmer, P., et al. (2007). Gender differences and determinants of aerobic fitness in children aged 8–11 years. European Journal of Applied Physiology, 99, 19–26. Edwards, N. M., Daniels, S. R., Claytor, R. P., Khoury, P. R., Dolan, L. M., Kimball, T. R., et al. (2012). Physical activity is independently associated with multiple measures of arterial stiffness in adolescents and young adults. Metabolism, 61, 869–872. Ferreira, I., van de Laar, R. J., Prins, M. H., Twisk, J. W., & Stehouwer, C. D. (2012). Carotid stiffness in young adults: A life-course analysis of its early determinants: The Amsterdam Growth and Health Longitudinal Study. Hypertension, 59, 54–61. Hodis, H. N., Mack, W. J., LaBree, L., Selzer, R. H., Liu, C. R., Liu, C. H., et al. (1998). The role of carotid arterial intima-media thickness in predicting clinical coronary events. Annals of Internal Medicine, 128, 262–269. Imholz, B. P., Settels, J. J., van der Meiracker, A. H., Wesseling, K. H., & Wieling, W. (1990). Non-invasive continuous finger blood pressure measurement during orthostatic stress compared to intra-arterial pressure. Cardiovascular Research, 24, 214–221. Joshi, D., Missiuna, C., Hanna, S., Hay, J., Faught, B. E., & Cairney, J. (2015). Relationship between BMI, waist circumference, physical activity and probable developmental coordination disorder over time. Human Movement Science, 40C, 237–247. Lingam, R., Hunt, L., Golding, J., Jongmans, M., & Emond, A. (2009). Prevalence of developmental coordination disorder using the DSM-IV at 7 years of age: A UK population-based study. Pediatrics, 123, e693–700. Litwin, M., Trelewicz, J., Wawer, Z., Antoniewicz, J., Wierzbicka, A., Rajszyz, P., et al. (2004). Intima-media thickness and arterial elasticity in hypertensive children: Controlled study. Pediatric Nephrology, 19, 767–774. Litwin, M., Niemirska, A., Sladowska, J., Antoniewicz, J., Daszkowska, J., Wierzbicka, A., et al. (2006). Left ventricular hypertrophy and arterial wall thickening in children with essential hypertension. Pediatric Nephrology, 21, 811–819. Meyer, A. A., Kundt, G., Steiner, M., Schuff-Werner, P., & Kienast, W. (2006). Impaired flow-mediated vasodilation, carotid artery intima-media thickening: and elevated endothelial plasma markers in obese children: the impact of cardiovascular risk factorsImpaired flow-mediated vasodilation, carotid artery intima-media thickening, and elevated endothelial plasma markers in obese children: The impact of cardiovascular risk factors. Pediatrics, 117, 1560–1567. Schott, N., Alof, V., Hultsch, D., & Meermann, D. (2007). Physical fitness in children with developmental coordination disorder. Research Quarterly for Exercise and Sport, 78, 438–450. Silman, A., Cairney, J., Hay, J., Klentrou, P., & Faught, B. E. (2011). Role of physical activity and perceived adequacy on peak aerobic power in children with developmental coordination disorder. Human Movement Science, 30, 672–681. Taylor, S. J., Whincup, P. H., Hindmarsh, P. C., Lampe, F., Odoki, K., & Cook, D. G. (2001). Performance of a new pubertal self-assessment questionnaire: A preliminary study. Paediatric and Perinatal Epidemiology, 15, 88–94. Tounian, P., Aggoun, Y., Dubern, B., Varille, V., Guy-Grand, B., Sidi, D., et al. (2001). Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: A prospective study. Lancet, 358, 1400–1404.
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Contents lists available at ScienceDirect
Research in Developmental Disabilities
Arterial stiffness in children with and without probable developmental coordination disorder Nicole E. Philips a , Daniele Chirico a , John Cairney b , John Hay c , Brent E. Faught c , Deborah D. O’Leary c,d,∗ a
Faculty of Applied Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada Department of Psychiatry and Behavioural Neuroscience, Family Medicine, Kinesiology, and CanChild, Centre for Childhood Disability Research, McMaster University, Hamilton, ON L8P 0A1, Canada c Department of Health Sciences, Brock University, St. Catharines, ON, Canada d Brock-Niagara Centre for Health and Well-Being, Brock University, St. Catharines, ON L2S 3A1, Canada b
a r t i c l e
i n f o
Article history: Received 10 February 2016 Received in revised form 26 June 2016 Accepted 24 July 2016 Number of reviews : 2 Keywords: Arterial stiffness Children Common carotid artery Developmental coordination disorder Distensibility Pulse wave velocity
a b s t r a c t Background: Children with cardiovascular disease risk factors demonstrate adverse arterial alterations that are predictive of cardiovascular morbidity and mortality in adults. Children with developmental coordination disorder (DCD) are at cardiovascular risk as they are more likely to be obese and inactive. Aim: The purpose of this study was to assess arterial structure and function in children with and without probable DCD (p-DCD). Methods: A cross-sectional study of 33 children with p-DCD (22 male) and 53 without (30 male). The Movement Assessment Battery for Children was used to classify those with p-DCD. Adiposity was assessed using the BOD POD. Compliance, distensibility, and intimamedia thickness were measured at the common carotid artery (CCA). ECG R-wave-to-toe pulse wave velocity (PWV) was also measured. Results: Compared to controls, males with p-DCD had lower CCA distensibility (p = 0.034) and higher PWV (p = 0.001). No differences were evident in females. Body fat percent was a significant predictor of CCA distensibility and removed the effect of p-DCD on PWV in males. Conclusions: The present study demonstrates augmented arterial stiffness in males with p-DCD, likely attributed to body fat. These findings underscore the importance of targeted interventions in children with p-DCD, specifically males, in order to prevent future cardiovascular risk. © 2016 Elsevier Ltd. All rights reserved.
What this paper adds Children with cardiovascular disease risk factors demonstrate adverse arterial alterations that are predictive of cardiovascular morbidity and mortality in adults. Children with developmental coordination disorder (DCD) are less likely to participate in physical activity and are more likely to be obese than their peers. Consequently, these children are at an increased risk of early arterial changes. However, no study has examined the link between DCD and arterial health in children. As a result, this study was the first to show that males with probable DCD (p-DCD) exhibit increased arterial stiffness
∗ Corresponding author at: Department of Health Sciences, Brock-Niagara Centre for Health and Well-Being, 500 Glenridge Ave, St. Catharines, Ontario, L2S 3A1, Canada. E-mail addresses: [email protected] (N.E. Philips), [email protected] (D. Chirico), [email protected] (J. Cairney), [email protected] (J. Hay), [email protected] (B.E. Faught), [email protected] (D.D. O’Leary). http://dx.doi.org/10.1016/j.ridd.2016.07.011 0891-4222/© 2016 Elsevier Ltd. All rights reserved.
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compared to controls; a finding that was attributed to excess adiposity in this population. In addition, this is the first study to show sex differences with respect to arterial health in children with p-DCD. No differences were seen in arterial health between females with and without p-DCD. As a result, males with p-DCD are at an increased risk for cardiovascular complications later in life. The results of this study highlight the importance of targeted interventions in children with p-DCD, specifically males with excess adiposity, in order to prevent future cardiovascular risk. 1. Introduction Developmental coordination disorder (DCD) is a neurological disorder with a global prevalence of approximately 1.8% of children, and is reported more often in boys (Lingam, Hunt, Golding, Jongmans, & Emond, 2009). Children with DCD exhibit poor motor skills and coordination, which adversely affects their participation in physical activity (Batey et al., 2014). Children with DCD also exhibit a greater prevalence of cardiovascular disease risk factors. Substantial research has illustrated that compared to their typically developing peers, children with DCD have greater body mass index (BMI) and waist circumference (Joshi et al., 2015), higher percent body fat (PBF) (Cairney, Hay, Veldhuizen, & Faught, 2011), greater prevalence of overweight/obesity (Cairney, Hay, Faught, & Hawes, 2005), lower cardiorespiratory fitness (Wu, Lin, Li, Tsai, & Cairney, 2010), and decreased physical fitness (Schott, Alof, Hultsch, & Meermann, 2007). Likewise, we have demonstrated that children with probable DCD (p-DCD), in comparison to their typically developing peers, have reduced autonomic regulation of blood pressure (BP) and atypical left ventricular structure and function, two supplementary markers of cardiovascular health (Chirico et al., 2011; Coverdale et al., 2012). Consequently, children with DCD are at an increased risk of developing cardiovascular disease. Noninvasive measures of arterial stiffness, such as reduced arterial distensibility and compliance, and increased pulsewave velocity (PWV) and arterial thickness (i.e., intima-media thickness [IMT]) are established predictors of cardiovascular morbidity and mortality in adults (Hodis et al., 1998; van Sloten et al., 2014; Vlachopoulos, Aznaouridis, & Stefanadis, 2010). These measures also demonstrate utility in identifying adverse arterial alterations in children who are less physically active, hypertensive or pre-hypertensive, and overweight. (Banach et al., 2010; Edwards et al., 2012; Urbina et al., 2011). Early arterial alterations in childhood may translate into accelerated cardiovascular risk in adulthood. Therefore, identification of children with heightened cardiovascular risk is critical. However, there are no studies evaluating arterial stiffness in children with DCD to our knowledge. The purpose of this investigation was to determine whether children diagnosed with p-DCD demonstrate increased arterial stiffness and thickness as measured by PWV, compliance, distensibility, and IMT of the common carotid artery (CCA) compared to age, sex and school matched controls. 2. Methods 2.1. Study population The sample was drawn from a larger population-based study known as the Physical Health Activity Study Team (PHAST) study, the details of which have been described previously (Cairney, Hay, Veldhuizen, & Faught, 2010). The Brock University Research Ethics Board and the District School Board of Niagara approved this study and consent/assent was provided by all parents/participants. There were 198 participants identified with p-DCD, scoring below the 10th percentile on the BruininksOseretsky Test of Motor Proficiency-Short Form (BOTMP-SF) during a health assessment in school. These individuals were invited by telephone to participate in annual lab-based assessments for three consecutive years, and a total of 63 agreed to participate. Healthy controls (63) were selected randomly from consenting students who scored above the 10th percentile on the BOTMP-SF and were matched for sex, school, and age within 6-months. All participants assessed in the lab were administered the Movement Assessment Battery for Children-2 (M-ABC2) to verify clinically significant motor coordination difficulties. The analyses reported are data collected from year three, and only includes those who completed all three years of the lab assessment. A total of 40 participants declined the invitation to return for the second and third years of assessment, resulting in a final sample size of 86 participants, of which, 33 had M-ABC2 scores ≤16th (p-DCD) and 53 controls scoring above the 16th percentile. 2.2. Experimental procedure Participants were scheduled for an appointment at the Applied Physiology Laboratories at Brock University. They were instructed to avoid strenuous physical activity/exercise twenty-four hours prior, as well as caffeine and food intake at least four hours prior to their assessment. Standing height, body mass and adiposity were assessed. Participants then entered the Human Hemodynamic Laboratory for cardiovascular measures. Once in the lab, participants were asked to lie supine for a period of 15 min to allow BP and heart rate (HR) to reach resting levels. Following this rest period, three manual BP measurements were taken with each measure separated by one minute. Participants then underwent five minutes of beat-by-beat HR, BP and PWV data collection. At the end of five minutes, right CCA ultrasound images were taken. Once data collection was complete, another three manual BP measurements were taken to ensure participants were still at rest.
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Upon completion of the cardiovascular assessment, participants were administered the M-ABC2 by a trained occupational therapist, followed by the completion of a peak oxygen uptake test (peak VO2 ). Finally, pubertal staging was completed seven to eight days following laboratory testing. 2.3. Measures 2.3.1. Anthropometrics Body mass index (BMI) was calculated using standing height and body mass (kg/m2 ). Standing height (cm) was measured using a stadiometer (Stat 7X, Ellard Instrumentation 50 Ltd Monroe, WA, USA) with the participants’ shoes removed and recorded to the nearest 0.1 cm. Body mass (kg) was measured using a digital scale (BWB-800S, Tanita Digital Scale, Tokyo, Japan) and recorded to the nearest 0.1 kg. Fat mass (FM), fat-free mass (FFM), and PBF were determined using whole body air-displacement plethysmography with the BOD POD (Life Measurement, Inc, Concord, CA), which has been explained in detail previously (Chirico et al., 2011). 2.3.2. Blood pressure and heart rate Brachial BP was taken using a standard inflatable cuff and sphygmomanometer placed on the right arm at heart level while participants rested in the supine position. Three measures were taken and averaged to provide systolic BP (SBP) and diastolic BP (DBP) values. In addition, five minutes of continuous beat-by-beat non-invasive BP was collected from the left middle finger using photoplethysmography (Nexfin, BMEYE, Amsterdam, The Netherlands). Since finger BP differs marginally from brachial BP, beat-by-beat BP was adjusted to the manual brachial BP to ensure accuracy (Imholz, Settels, van der Meiracker, Wesseling, & Wieling, 1990). A one-minute average of SBP, DBP and mean arterial pressure (MAP = 1/3·SBP + 2/3·DBP) was determined. Likewise, HR was collected using a standard one-lead ECG and a one-minute R-R interval (RRI) average was used to calculate HR by dividing the average RRI (sec) into 60. 2.3.3. Vascular measures Central compliance and distensibility were measured at the right CCA using non-invasive Echo-Doppler ultrasound (Vivid I, GE Medical Systems, Horton, Norway). Images were taken while participants were supine using an 8 MHz linear array transducer approximately 1–2 cm proximal to the carotid artery bifurcation. Three images consisting of five beat-by-beat diameter changes were taken for each subject using high resolution B-mode. The two best images were selected, based on image quality, to measure CCA compliance and distensibility. The best three beats from each image were chosen and diameters corresponding to systole and diastole were measured using computer automated edge detection software (Artery Measurement System II, Image and Data Analysis). Lumen diameter (LD) was measured from the leading edge of the near wall intima to the leading edge of the far wall intima. Intima-media thickness (IMT) was measured at end-diastole at the far wall for the same cardiac cycles as diameters. Pulsatile cross sectional area (CSA; r2 , where r = diameter/2) and corresponding finger pressures were used to determine CCA compliance and distensibility using the following equations: Compliance = (sCSA − dCSA)/(Ps − Pd ) and Distensibility = ((sCSA − dCSA)/dCSA)/(Ps − Pd ) where sCSA and dCSA are systolic and diastolic cross-sectional areas and Ps and Pd are systolic and diastolic finger pressures, respectively. Pulse wave velocity (PWV) was measured noninvasively using ECG and the pulse wave at the left second toe (Nellcor N-200 Tyco Healthcare Group LP, Pleasanton, Calif., USA); a similar method has been used in children (Currie, Proudfoot, Timmons, & MacDonald, 2010). The time delay between the R peak on the ECG to the beginning of the upstroke of the pressure waveform was used to calculate pulse transit time (s), averaged over ten consecutive beats. Distance (m) was measured from the sternal notch to the left middle toe. PWV was calculated using the following equation: PWV(m/s) = (Distance)/(TransitTime)
2.3.4. Assessment of motor coordination Motor coordination of all participants was assessed each year by a trained occupational therapist using the M-ABC2. As children may perform better or worse depending on the conditions or the day, an average score for the 3 years was used to accurately identify children with motor impairments. Scores were converted into percentiles and those with averages below the 16th percentile were identified as p-DCD. Probable cases of DCD were identified as p-DCD due to the fact that information about criterion B from the DSM-V was missing (American Psychiatric Association, 2013). In addition, the Kaufman Brief Intelligence Test was administered by the occupational therapist to verify participants’ intellectual ability and to satisfy criterion D from the DSM-V (American Psychiatric Association, 2013).
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2.3.5. Aerobic fitness A peak VO2 test using a programmed cycle ergometer (Excalibur Sport V2, Lode BV, Groningen, The Netherlands) was used to measure peak aerobic power. This procedure consists of a continuous and incremental exercise protocol, which has been previously described (Silman, Cairney, Hay, Klentrou, & Faught, 2011). Criteria used to assess achievement of peak aerobic power required at least two of the following: (1) a respiratory gas exchange ratio of at least 1.0; (2) HR was greater than 85% of theoretical maximal level for age (220-age); and/or (3) physical signs of intense effort (facial flushing, or difficulty maintaining speed cycle) (Armstrong and Van Mechelem, 2008; Dencker et al., 2007). For between group comparisons, peak VO2 was adjusted for FFM (peak VO2FFM ), which has been shown to be the most appropriate method for normalizing for body size (Dencker et al., 2007). 2.3.6. Maturation Pubertal maturation was self-reported using pictures of the Sexual Maturation Scale for pubic hair and genitalia development by Tanner and taken from Taylor et al. (2001). Each subject completed the self-assessment at home seven to eight days following laboratory testing, in the presence of his or her parent(s), and placed it in an envelope to maintain confidentiality. Three male controls did not complete the Tanner scale. 2.4. Statistical analysis Statistical analyses were carried out using SPSS software version 20.0 for Windows (IBM SPSS Statistics 20) and the level of significance was set at p ≤ 0.05. Multivariable linear regressions were performed to determine whether the effect of p-DCD on PWV, IMT, compliance and distensibility varied by sex (a sex by p-DCD interaction). Due to a significant sex by p-DCD interaction for PWV and distensibility (p < 0.05), all descriptive statistics for participants with p-DCD (average M-ABC2 over 3 years < 16th percentile) and controls (average M-ABC2 over 3 years ≥ 16th percentile) are reported separately for males and females. Independent t-tests and chi-square tests were used to examine differences in experimental measures between children with and without p-DCD in both populations. Results are expressed as mean (SD). To address the study’s intended purpose, two separate multivariable linear regressions were performed in males to examine the effect of p-DCD on PWV and p-DCD on distensibility. Relevant variables differing between groups were controlled for (i.e. HR, VO2FFM and PBF) and values are presented as regression coefficients. All variables were checked for normality using the Shapiro-Wilk test. Although several variables were not normally distributed, after performing Mann Whitney U tests for these variables the results remained unchanged. Given that the results do not change with non-parametric analyses, and the sample size is large (>30), we continue to report parametric analyses. 3. Results 3.1. Sample characteristics Table 1 presents group differences separated by sex for demographic, anthropometric, and cardiovascular variables. The p-DCD group had lower M-ABC2 scores compared to controls, while age and K-BIT were not different between groups for males or females. For anthropometric measures, body mass, BMI, PBF and FM were higher in the p-DCD group (p < 0.01) in males. In females, only PBF was significantly greater in the p-DCD group (p = 0.028). For cardiovascular measures, HR was higher (p = 0.014) and peak VO2FFM was lower (p = 0.008) in males with p-DCD compared to controls. Peak VO2 (p = 0.003) and peak VO2FFM (p = 0.030) were lower in females with p-DCD compared to controls. Finally, sexual maturation was not different between groups for males or females. 3.2. Arterial characteristics Characteristics of arterial structure and function are shown in Table 2 and are presented separately by group (p-DCD versus control) and sex. Due to inadequate image quality and missing data: 7 male and 4 female participants were excluded from analysis of compliance, distensibility and IMT, and 6 male and 6 female participants were excluded from PWV analysis. Diastolic diameter (p = 0.026) and PWV (p = 0.001) were greater, while distensibility (p = 0.034) was lower in the p-DCD group compared to controls in males. There were no group differences in arterial structure and function in females. Sex differences in distensibility and PWV were confirmed using multivariate linear regression. PWV and distensibility were analyzed based on two models; 1) effect of p-DCD, 2) p-DCD adding sex and the sex/p-DCD interaction (Table 3). In model one, examining p-DCD and PWV, the main effect of p-DCD was positive and significant (p = 0.016), accounting for 6.5% of the variability in PWV (R2 adjusted = 0.065). When sex and the sex/p-DCD interaction term were entered in model two, the interaction term was significant (p = 0.010), accounting for ∼16% of the variability (R2 adjusted = 0.156). Furthermore, in the first model examining p-DCD and distensibility, the main effect of p-DCD was not significant (p = 0.389). However, when sex and the sex/p-DCD interaction were added in model two, the interaction term was significant (p = 0.013), accounting for 7% of the variability (R2 adjusted = 0.071). These interactions are illustrated in Fig. 1. Since the effect of p-DCD was only found to be a significant predictor of PWV and distensibility in males, further analysis focused only on this population. Multivariable regression analyses consisting of four models were implemented to test
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Table 1 Demographic and cardiovascular characteristics for male and female children with p-DCD and controls. Male
Female
p-DCD
Control
p-value
p-DCD
Control
p-value
Demography Age (y:mo) M-ABC2 (percentile) K-BIT
n = 22 14:10 (0:6) 7.0 (4.6) 94 (11.6)
n = 30 14:8 (0:5) 48.7 (14.8) 99 (10.8)
0.357 0.001 0.146
n = 11 14:6 (0:5) 7.5 (3.8) 88 (16.2)
n = 23 14:7 (0:6) 48.0 (20.1) 96 (7.9)
0.172 0.000 0.119
Anthropometry Height (cm) Body Mass (kg) BMI (kg/m2 ) PBF FM (kg) FFM (kg)
172.4 (6.5) 78.3 (24.4) 26.2 (7.2) 27.8 (11.5) 23.6 (15.5) 54.7 (11.9)
172.8 (5.3) 59.7 (8.2) 20.1 (2.5) 12.5 (6.8) 7.7 (5.1) 53.5 (9.0)
0.821 0.002 0.001 0.000 0.000 0.685
161.6 (6.7) 63.8 (15.6) 24.4 (4.6) 32.1 (9.7) 21.5 (10.3) 42.3 (6.5)
163.9 (5.7) 61.1 (11.9) 22.8 (4.2) 25.3 (7.1) 16.1 (7.4) 45.0 (6.2)
0.303 0.584 0.331 0.028 0.086 0.237
Cardiovascular Variables SBP (mmHg) DBP (mmHg) MAP (mmHg) HR (bpm) Peak VO2 (L/min) Peak VO2 (mL/kgFFM /min)
113 (13) 64 (10) 80 (10) 74.9 (13.1) 3.0 (0.7) 54.7 (7.7)
108 (11) 60 (11) 76 (10) 67.0 (9.3) 3.3 (0.5) 61.9 (10.3)
0.149 0.192 0.129 0.014 0.089 0.008
105 (10) 64 (10) 77 (9) 73.6 (8.6) 2.0 (0.3) 47.8 (7.1)
111 (10) 68 (12) 82 (10) 71.1 (8.8) 2.4 (0.5) 53.9 (7.4)
0.097 0.223 0.142 0.444 0.003 0.030
Mean (SD) Independent-samples t-test. p-DCD = probable Developmental Coordination Disorder, y = years, mo = months, M-ABC2 = Movement Assessment Battery for Children 2nd edition, K-BIT = Kaufmann Brief Intelligence Test, BMI = Body Mass Index, PBF = Percent Body Fat, FM = Fat Mass, FFM = Fat Free Mass, SBP = Systolic Blood Pressure, DBP = Diastolic Blood Pressure, MAP = Mean Arterial Pressure, HR = Heart Rate, bpm = beats per minute, VO2 = Peak Aerobic Fitness. Table 2 Arterial measures in children with p-DCD and controls by sex. Male
Female
p-DCD
Control
p-value
p-DCD
Control
p-value
Arterial Diameters Systolic (mm) Diastolic (mm) Difference (mm)
n = 18 6.55 (0.41) 5.64 (0.45) 0.87 (0.22)
n = 27 6.29 (0.57) 5.31 (0.48) 0.97 (0.23)
0.103 0.026 0.171
n = 10 6.06 (0.50) 5.23 (0.40) 0.86 (0.18)
n = 20 6.15 (0.47) 5.36 (0.40) 0.77 (0.17)
0.608 0.379 0.260
Arterial Stiffness PP (mmHg) PWV (m/s) Compliance (mm2 /mmHg) Distensibility (mmHg−1 × 10−2 )
52.2 (13.5) 4.1 (0.3) (n = 20) 0.17 (0.03) 0.70 (0.17)
50.5 (9.2) 3.8 (0.2) (n = 26) 0.18 (0.05) 0.82 (0.19)
0.619 0.001 0.506 0.034
44.2 (7.2) 3.8 (0.4) (n = 9) 0.17 (0.05) 0.79 (0.14)
46.3 (7.3) 3.8 (0.3) (n = 19) 0.16 (0.05) 0.70 (0.15)
0.464 0.523 0.492 0.123
Arterial Thickness IMT (mm)
0.39 (0.04)
0.40 (0.05)
0.483
0.39 (0.03)
0.39 (0.05)
0.981
Mean (SD) Independent-samples t-test. p-DCD = probable Developmental Coordination Disorder, PP = Pulse Pressure, PWV = Pulse Wave Velocity, IMT = Intima-Media Thickness.
A
B 0.82
4.2
PWV (m/s)
4 3.9
Male Female
3.8 3.7 3.6
Distensibility (mmHg -1 x 10 -2)
0.8
4.1
0.78 0.76 0.74
Male
0.72
Female
0.7 0.68 0.66 0.64
3.5 p-DCD
Control
p-DCD
Control
Fig. 1. Interaction between sex and probable Developmental Coordination Disorder (p-DCD) with respect to a) pulse wave velocity (PWV) (p = 0.010) and b) distensibility (p = 0.013).
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Table 3 Multivariable linear regression of p-DCD on PWV and distensibility.
PWV Model 1 Constant p-DCD Model 2 Constant p-DCD Sex Sex*p-DCD Distensibility Model 1 Constant p-DCD Model 2 Constant p-DCD Sex Sex*p-DCD
R
R2
R2 adjusted
(n = 74) 0.279
0.078
0.065
0.436
0.190
(n = 75) 0.101
Bstandardized
p-value
3.828 0.169
0.280
0.000 0.016
3.819 0.284 0.021 −0.361
0.469 0.034 −0.400
0.000 0.001 0.803 0.010
0.008 0.000
−0.101
0.000 0.389
0.008 −0.001 −0.001 0.002
−0.334 −0.344 0.414
0.000 0.022 0.017 0.013
0.156
−0.003
0.010
0.329
bunstandardized
0.108
0.071
PWV = pulse wave velocity, p-DCD = probable Developmental Coordination Disorder. Table 4 Multivariable linear regression of p-DCD on PWV and distensibility in males. R2
R2 adjusted
bunstandardized
Bstandardized
p-value
PWV (n = 46) Model 1 Model 2 Model 3 Model 4
0.236 0.257 0.282 0.293
0.218 0.223 0.231 0.224
0.284 0.249 0.226 0.171
0.485 0.426 0.387 0.293
0.001 0.004 0.011 0.124
Distensibility (n = 45) Model 1 Model 2 Model 3 Model 4
0.100 0.131 0.138 0.246
0.079 0.089 0.075 0.171
−0.001 −0.001 −0.001 0.0001
−0.316 −0.266 −0.236 0.021
0.034 0.082 0.146 0.910
Model 1–unadjusted. Model 2–adjusted for heart rate. Model 3–adjusted for heart rate and peak VO2FFM . Model 4–adjusted for heart rate, peak VO2FFM , and body fat percent.
the independent effect of p-DCD on PWV and distensibility in males, while adjusting for covariates (Table 4). For PWV, in models 1–3, it was shown that p-DCD was an independent predictor of PWV. However, when adding PBF (model 4), p-DCD was no longer an independent predictor. None of the covariates were significant predictors of PWV. For distensibility, after controlling for HR (model 2), p-DCD was no longer a significant predictor, which remained true for models 3 and 4 as well. Only PBF (model 4) was a significant predictor of distensibility (p = 0.022). 4. Discussion The purpose of this study was to determine whether children with p-DCD demonstrate greater arterial stiffness than typically developing peers. The primary finding was a sex/p-DCD interaction effect on PWV and distensibility; males with pDCD had faster PWV and reduced distensibility compared to controls, while no difference was seen in females. The augmented PWV and attenuated distensibility in p-DCD males may be attributed to a higher PBF, as it removed the main effect on PWV and was a significant predictor of distensibility. In addition, it was found that males with p-DCD exhibited significant differences in HR and peak VO2FFM , while females with p-DCD demonstrated significant differences in peak VO2 and VO2FFM . Based on current literature, possible explanations to the sex-dependent increase in arterial stiffness associated with pDCD include overweight/obesity, and physical inactivity (Edwards et al., 2012; Tounian et al., 2001). In a study examining the effect of physical activity in children with p-DCD, Batey et al. (2014) determined that physical activity is reduced in males with DCD, but not in females, compared to controls. These authors found that males and females with p-DCD, and females without p-DCD demonstrated similar time spent in moderate to vigorous physical activity, while males without p-DCD spent a significantly greater amount of time in moderate to vigorous physical activity. Activity levels in males are therefore more susceptible to p-DCD status and likely contribute to differences in arterial stiffness in the present study. A recent study by Joshi et al. (2015) examined the long-term impact of p-DCD on BMI and waist circumference over a five-year period. It was found that BMI and waist circumference were elevated in those with p-DCD, and these differences
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increased over time in males, but not females. Although physical activity did not affect this relationship, it was negatively correlated with BMI and waist circumference. As well, it has been demonstrated that PBF is greater in children with DCD (Cairney et al., 2011), and the prevalence of overweight/obesity is greater in males with p-DCD compared to controls, but not females (Cairney et al., 2005). Consistent with these findings, male children with p-DCD in the present study have increased fat mass and PBF compared to controls (Cairney et al., 2011). Taken together, previous findings demonstrate sex-specific effects of p-DCD on health outcomes and the current study further extends these differences to increased arterial stiffness in males with p-DCD, but not females when compared to healthy peers. The measure of PWV in the present study differs slightly from the gold-standard. Typically, PWV is measured from the carotid and femoral arteries whereas we measured PWV from the peak of the R-wave to the toe. A similar method of measuring PWV has shown to be feasible and reliable in children (Currie et al., 2010) and provides a practical option in our population. This method is not only less time consuming, but is also less dependent on operator skill and participant compliance and may be useful for large-scale studies of arterial health in child populations, such as this one. In comparing our values to Currie et al. (2010), they are slightly higher (3.8 and 4.1 m/s versus 3.5 ± 0.3 m/s). This is to be expected as Currie and colleagues examined pre-school aged children, whereas the present study investigated children with an average age of 14 years. PWV has been shown to increase with age (Voges et al., 2012), as well as demonstrate a maturation/sex interaction (Ahimastos, Formosa, Dart, & Kingwell, 2003). However, these factors are not believed to have impacted the results as groups were matched for age and sex, and maturation was not significantly different between p-DCD and controls. There was no difference in CCA compliance between groups in the present study. Compliance is a size dependent measure of arterial stiffness and differences between groups may have been masked by the fact that males with p-DCD had higher diastolic diameters compared to controls. Nevertheless, CCA distensibility was significantly lower in males with p-DCD compared to controls. When controlling for covariates this difference was no longer significant, with PBF being the only significant predictor of distensibility. These findings are similar to that of Banach et al. (2010), and Tounian et al. (2001) who found an increase in diastolic diameter and a decrease in CCA distensibility in overweight/obese children. As well, we have demonstrated that CCA distensibility negatively correlates with PBF and positively correlates with peak VO2FFM (Banach et al., 2010). Therefore, the finding of diminished CCA distensibility in males in the present study is supported by previous research suggesting that body fat and aerobic fitness are important determinants of distensibility. In contrast to arterial stiffness measures, IMT was not different between p-DCD and controls. Evidence suggests that IMT can be augmented in children with obesity and high BP (Litwin et al., 2004, 2006; Urbina et al., 2011). However, it is critical to highlight that the average BMI and BP values in the present study are considerably lower than studies assessing the effect of obesity and high BP on IMT. For example, Meyer, Kundt, Steiner, Schuff-Werner, and Kienast, 2006 examined obesity and IMT in children (aged 9–16 years) whose mean BMI was 30.6 kg/m2 compared to 20.4 kg/m2 in controls. In contrast, p-DCD children in the current study had a mean BMI of 25.6 kg/m2 , while controls had a mean BMI of 21.3 kg/m2 . Likewise, studies assessing the effect of elevated BP on IMT in children have compared clinically hypertensive children to those that are normotensive (Litwin et al., 2004, 2006; Urbina et al., 2011). In contrast, BP values in the present study for both groups were within the normal range. However, in support of our findings, a study by Aggoun et al. (2008) reported that arterial stiffness was elevated in obese children aged 8.8 years old, compared to controls; although, IMT was not different. This suggests that alterations in arterial stiffness (PWV and distensibility) may precede changes in arterial structure (IMT). Support for the importance of early cardiovascular modification on future health is emphasized in literature demonstrating small differences in cardiovascular disease risk in childhood can predict risk of atherosclerotic development in adulthood (Ferreira, van de Laar, Prins, Twisk, & Stehouwer, 2012). For example, in the Amsterdam Growth and Health Longitudinal Study, a 24-year follow-up revealed that individuals in the lowest tertile of carotid distensibility (greater stiffness) at age 36 demonstrated elevated BMI at 15 years old, compared to those in the highest tertile (Ferreira et al., 2012). These findings underscore the importance of childhood as a critical time period in which early alterations can result in accelerated future risk. Likewise, small differences in PWV and distensibility are perceived to be important as minimal increases in PWV (1 m/s) and decreases in distensibility (1 SD) have been shown to significantly increase risk of cardiovascular and all-cause mortality in adults (van Sloten et al., 2014; Vlachopoulos, Aznaouridis, & Stefanadis, 2010). Although males with p-DCD demonstrate PWV and distensibility values within the normal range, the augmented arterial stiffness remains concerning as it is likely to predict increased risk in adulthood. These results emphasize the importance of targeting interventions at a young age in children with p-DCD as to prevent an augmented risk of cardiovascular disease in adulthood.
4.1. Limitations First, we were unable to confirm whether the motor impairments experienced by children with p-DCD significantly interfered with activities of daily living and/or academic performance. As a result, we were unable to meet the full criteria of the DSM-V and therefore identified children as having p-DCD. Second, since this is an ancillary cross-sectional design within a larger longitudinal study, we cannot make causal links between p-DCD and cardiovascular risk. Tracking arterial changes over time in children with p-DCD will provide a better understanding of how arterial structure and function are altered in this population. Lastly, power to detect a difference in distensibility was low for females. Therefore, we cannot say with certainty that arterial changes within this population were absent. However, this is not believed to have influenced
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the interpretation of the results as it was shown that females with p-DCD had greater (non-significant) distensibility than TD controls, while PWV was identical. 5. Conclusion This was the first study to examine arterial health in children with p-DCD. Males with p-DCD exhibited augmented arterial stiffness via faster PWV and diminished carotid distensibility compared to controls, while females did not. The increased arterial stiffness in males with p-DCD can be attributed to excess adiposity. As a result, it is apparent that sex differences exist with respect to arterial health within this population and that males with p-DCD may be more likely to develop arterial stiffness later in life. The results of this study highlight the necessity of targeted interventions in children with p-DCD, specifically males with excess adiposity, in order to prevent future cardiovascular risk. Acknowledgements This study was funded by the Canadian Institutes of Health Research (grant no. 66959). 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