**5. Results**

Analysis of the values of the minimum PWV (PWVmin), mean PWV (PWVmean) and maximum PWV (PWVmax) obtained during 24-hour blood pressure monitoring revealed statistically significant differences between the main and control groups (p < 0.001) (**Figure 1**). The presence of FHC was accompanied by a significant increase in PWV - minimum, mean and maximum values.

Taking into account the results obtained, we analyzed the degree of change in PWV depending on the age of children. For the analysis, both groups were divided into 3 age subgroups: from 5 to 7 years old, from 8 to 12 years old, from 13 to 17 years old (**Table 2**).

In accordance with the results obtained, in the younger age subgroup (5–7 years old), there were no statistically significant differences in PWV between the children of the main and control groups. In children aged 8–12 years, there was no statistically significant difference in the values of PWV min and mean PWV. While PWVmax was characterized by statistically significantly higher values in the main group (5.1 [4.7–5.8] m/s) relative to the control (4.6 [4.45–5.05] m/s) (p = 0.041). The most pronounced changes were found in the group of children with FHC at the age of 13–17 years. In this group were revealed statistically significant differences in the minimum, mean and maximum pulse wave velocity.

Taking into account the peculiarities of physical parameters and age periodization, we have analyzed the dynamics of changes in PWV depending on the age of children. In children of the control group, PWVmin in children 8–12 year old was statistically significantly higher than in children 5–7 year old (3.6 [3.2–4.1] m/s and 3.0 [2.8–3.1] m/s, respectively, p = 0.049). When comparing PWVmin in groups of 8–12 years old children and 13–17 years old children, no statistically significant difference was found (3.6 [3.2–4.1] m/s and 3.9 [3.5–4.1] m/s, respectively, p = 0.052). A similar dynamics of growth was observed for the mean pulse wave velocity in healthy children when compared in age subgroups 8–12 years old and 5–7 years old (4.3 [3.7–5.1] m/s and 3.8 [3.7–3.9] m/s, respectively, p = 0.026) and 8–12 years old and 13–17 years old (4.3 [3.7–5.1] m/s and 4.5 [4.2–4, 9] m/s, respectively, p = 0.114).

**Figure 1.**

*Comparison of the values of the pulse wave velocity in the main and control groups. Note: \*\*\* - p < 0.001.*

**101**

**Table 4.**

**Table 3.**

*Arterial Stiffness Assessment in Children with Familial Hypercholesterolemia*

5–7 years (n = 15) 5–7 years (n = 16) PWVmin 3,0 2,8-3,1 3,05 2,6-3,3 0,19 PWVmean 3,8 3,7-3,9 4,1 3,8-4,1 0,19 PWVmax 4,5 4,3-4,8 4,8 4,1-5,3 0,095 8–12 years (n = 22) 8–12 years (n = 21) PWVmin 3,6 3,2-4,1 3,5 3,3-3,9 0,052 PWVmean 4,3 3,7-5,1 4,6 4,0-5,0 0,05 PWVmax 4,6 4,45-5,05 5,1 4,7-5,8 0,041 13–17 years (n = 21) 13–17 years (n = 23) PWVmin 3,9 3,5-4,1 4,7 4,1-5,1 0,009 PWVmean 4,5 4,2-4,9 5,5 4,8-6,4 0,009 PWVmax 5,4 5,05-5,6 6,2 5,7-7,55 0,007

**Control group Main group p**

**Me Q1-Q3 Me Q1-Q3**

The analysis of PWVmax showed that these indicators in the group of 5–7 years old and 8–12 years old children did not significantly differ from each other (4.5 [4.3–4.8] m/s and 4.6 [4.45–5.05] m/s, p = 0.145), while in children 13–17 years old it was significantly higher in comparison with 8–12 years old children (5.4 [5.05–5.6] m/s and 4.6 [4, 45–5.05] m/s, respectively, p = 0.022). It should be noted that there is a statistically significant difference in the values of PWVmin, mean PWV and PWVmax in children 13–17 years old relatively to 5–7 years old (**Table 3**).

*Comparison of the values of the pulse wave velocity depending on the age of the children.*

The study of PWV in children of the main group revealed a statistically significant difference in the increase in PWVmin, mean PWV and PWVmax indicators

**Parameter, m/s 5–7 years 8–12 years 13-17 years** Р**1–2** Р**2–3** Р**1–3 PWVmin** 3,0 [2,8-3,1] 3,6 [3,2-4,1] 3,9 [3,5-4,1] **0,049** 0,052 **0,043 PWVmean** 3,8 [3,7-3,9] 4,3 [3,7-5,1] 4,5[4,2-4,9] **0,026** 0,114 **0,047 PWVmax** 4,5 [4,3-4,8] 4,6 [4,45-5,05] 5,4 [5,05-5,6] 0,145 **0,022 0,018**

**Parameter, m/s 5–7 years 8–12 years 13–17 years** Р**1–2** Р**2–3** Р**1–3 PWVmin** 3,05[2,6-3,3] 3,5 [3,3-3,9] 4,7 [4,1-5,1] **0,001 0,004 0,008 PWVmean** 4,1 [3,8-4,1] 4,6 [4,0-5,0] 5,5[4,8-6,4] **0,001 0,016 0,004 PWVmax** 4,8 [4,1-5,3] 5,1 [4,7-5,8] 6,2 [5,7-7,55] **0,028 0,021 0,018**

*DOI: http://dx.doi.org/10.5772/intechopen.96018*

**Parameter m/s**

**Table 2.**

when compared in all main groups (**Table 4**).

*Note: p is the level of significance of the differences.*

*Note: p is the level of significance of the differences.*

*Indicators of the pulse wave velocity of children of the control group.*

*Indicators of the pulse wave velocity of children of the main group.*


*Arterial Stiffness Assessment in Children with Familial Hypercholesterolemia DOI: http://dx.doi.org/10.5772/intechopen.96018*

**Table 2.**

*Management of Dyslipidemia*

17 years old (**Table 2**).

Analysis of the values of the minimum PWV (PWVmin), mean PWV (PWVmean) and maximum PWV (PWVmax) obtained during 24-hour blood pressure monitoring revealed statistically significant differences between the main and control groups (p < 0.001) (**Figure 1**). The presence of FHC was accompanied

by a significant increase in PWV - minimum, mean and maximum values.

the minimum, mean and maximum pulse wave velocity.

Taking into account the results obtained, we analyzed the degree of change in PWV depending on the age of children. For the analysis, both groups were divided into 3 age subgroups: from 5 to 7 years old, from 8 to 12 years old, from 13 to

In accordance with the results obtained, in the younger age subgroup (5–7 years old), there were no statistically significant differences in PWV between the children of the main and control groups. In children aged 8–12 years, there was no statistically significant difference in the values of PWV min and mean PWV. While PWVmax was characterized by statistically significantly higher values in the main group (5.1 [4.7–5.8] m/s) relative to the control (4.6 [4.45–5.05] m/s) (p = 0.041). The most pronounced changes were found in the group of children with FHC at the age of 13–17 years. In this group were revealed statistically significant differences in

Taking into account the peculiarities of physical parameters and age periodization, we have analyzed the dynamics of changes in PWV depending on the age of children. In children of the control group, PWVmin in children 8–12 year old was statistically significantly higher than in children 5–7 year old (3.6 [3.2–4.1] m/s and 3.0 [2.8–3.1] m/s, respectively, p = 0.049). When comparing PWVmin in groups of 8–12 years old children and 13–17 years old children, no statistically significant difference was found (3.6 [3.2–4.1] m/s and 3.9 [3.5–4.1] m/s, respectively, p = 0.052). A similar dynamics of growth was observed for the mean pulse wave velocity in healthy children when compared in age subgroups 8–12 years old and 5–7 years old (4.3 [3.7–5.1] m/s and 3.8 [3.7–3.9] m/s, respectively, p = 0.026) and 8–12 years old and 13–17 years old (4.3 [3.7–5.1] m/s and 4.5 [4.2–4, 9] m/s, respectively, p = 0.114).

*Comparison of the values of the pulse wave velocity in the main and control groups. Note: \*\*\* - p < 0.001.*

**5. Results**

**100**

**Figure 1.**

*Comparison of the values of the pulse wave velocity depending on the age of the children.*

The analysis of PWVmax showed that these indicators in the group of 5–7 years old and 8–12 years old children did not significantly differ from each other (4.5 [4.3–4.8] m/s and 4.6 [4.45–5.05] m/s, p = 0.145), while in children 13–17 years old it was significantly higher in comparison with 8–12 years old children (5.4 [5.05–5.6] m/s and 4.6 [4, 45–5.05] m/s, respectively, p = 0.022). It should be noted that there is a statistically significant difference in the values of PWVmin, mean PWV and PWVmax in children 13–17 years old relatively to 5–7 years old (**Table 3**).

The study of PWV in children of the main group revealed a statistically significant difference in the increase in PWVmin, mean PWV and PWVmax indicators when compared in all main groups (**Table 4**).


#### **Table 3.**

*Indicators of the pulse wave velocity of children of the control group.*


#### **Table 4.**

*Indicators of the pulse wave velocity of children of the main group.*

#### *Management of Dyslipidemia*

At the same time, a more significant dynamics of increase in PWV was observed in children with FH compared with the control group in the age range of 13–17 years (**Figure 2**). It should be noted that the dynamics of the increase in indicators in the control group was less than in children with FH (**Figure 3**).

Taking into account the presence of dyslipidemia in patients with FH in the form of severe hypercholesterolemia, we performed a correlation analysis of the relationship between PWV values and lipid metabolism indicators. In the main group, statistically significant direct correlations were established between PWVmin, mean PWV and PWVmax with total cholesterol level (rxy = 0.46 [95% CI: 0.227– 0.644], rxy = 0.46 [95% CI: 0.229–0.642] and rxy = 0.464 [95% CI: 0.234–0.645], respectively, p < 0.001 in all cases).

#### **Figure 2.**

*Indicators of the pulse wave velocity of the main and control groups, depending on the age of the children. Note: PWVmin - minimum pulse wave velocity, PWVmean - mean pulse wave velocity, PWVmax - maximum pulse wave velocity.*

#### **Figure 3.**

*Dynamics of the increase in the mean pulse wave velocity in the main and control groups, depending on the age of the children. Note: \* - p = 0.009.*

**103**

**7. Conclusion**

the disease

**Conflict of interest**

Authors declare no conflict of interest.

*Arterial Stiffness Assessment in Children with Familial Hypercholesterolemia*

correctness and statistical significance of the obtained results.

In the presented study, the condition of the arterial wall was assessed by measuring the pulse wave velocity in the aorta in children with FH and healthy children of the same age. The study design differs from previous studies of PWV in the pediatric population presented in the literature [33–36] in distribution of participants into age subgroups. In our opinion, such an analysis of the PWV values increases the

We found that the PWV values of children of the main group at the age of 5–7 years do not differ from those of the control group. In the 8–12-year-old subgroup in patients with FH, only the maximum PWV indicators were statistically significantly higher than in the comparison group. The identified deviations probably reflect the initial changes in the stiffness of the vascular wall in children of the main group. The most pronounced differences in the studied parameters were observed in children with FH in the age subgroup of 13–17 years old and were characterized by a statistically significant increase in PWVmin, mean PWV and

In our study, we also analyzed the dynamics of PWV growth depending on age. It was shown that PWV values increase with the age of the child both in familial hypercholesterolemia and in healthy children. This indicates that the studied indicators cannot be the same for all children and it is necessary to use age reference values in pediatrics. In addition, the increase in all three values of PWV was most pronounced in the group of 13–17 year old patients with FH, it allows us to suggest that they have a more pronounced change of properties of the vascular wall already

A number of studies have revealed an increased PWV in children with hypertension [37], increased body mass index [38, 39]. In the present study, special attention was paid to patients with FH without risk factors such as smoking, obesity, and high blood pressure. Thus, the authors were able to assess the effect of hypercholesterolemia on the change in PWV precisely. The established correlation between total cholesterol level and PWV values allows us to regard an increase in total cholesterol level as a leading factor in forming the arterial stiffness in children with FH. In addition, the registration of the initial changes in PWV in the group with FH from 8–12 years old with further progression of the process in the absence of such changes in children 5–7 years old indicates a possible cumulative effect of cholesterol and its effect on the artery wall condition. This is consistent with large randomized studies showing that the effect of LDL on the development of atherosclerotic vascular disease is determined not only by the absolute level of LDL, but

Thus, the relationship between cholesterol level, age, and arterial stiffness indicators in familial hypercholesterolemia makes it possible to recommend the study of pulse wave velocity as a possible additional method for studying the cardiovascular risk in children with familial hypercholesterolemia and assessing the progression of

at preclinical stages than in individuals with normal blood lipid profile.

also by its cumulative effect on target organs [2, 40, 41].

*DOI: http://dx.doi.org/10.5772/intechopen.96018*

PWmax relatively to the control group.

**6. Discussion**

*Arterial Stiffness Assessment in Children with Familial Hypercholesterolemia DOI: http://dx.doi.org/10.5772/intechopen.96018*

## **6. Discussion**

*Management of Dyslipidemia*

respectively, p < 0.001 in all cases).

At the same time, a more significant dynamics of increase in PWV was observed in children with FH compared with the control group in the age range of 13–17 years (**Figure 2**). It should be noted that the dynamics of the increase in indicators in the

Taking into account the presence of dyslipidemia in patients with FH in the form of severe hypercholesterolemia, we performed a correlation analysis of the relationship between PWV values and lipid metabolism indicators. In the main group, statistically significant direct correlations were established between PWVmin, mean PWV and PWVmax with total cholesterol level (rxy = 0.46 [95% CI: 0.227– 0.644], rxy = 0.46 [95% CI: 0.229–0.642] and rxy = 0.464 [95% CI: 0.234–0.645],

*Indicators of the pulse wave velocity of the main and control groups, depending on the age of the children. Note: PWVmin - minimum pulse wave velocity, PWVmean - mean pulse wave velocity, PWVmax - maximum pulse* 

*Dynamics of the increase in the mean pulse wave velocity in the main and control groups, depending on the age* 

control group was less than in children with FH (**Figure 3**).

**102**

**Figure 3.**

*of the children. Note: \* - p = 0.009.*

**Figure 2.**

*wave velocity.*

In the presented study, the condition of the arterial wall was assessed by measuring the pulse wave velocity in the aorta in children with FH and healthy children of the same age. The study design differs from previous studies of PWV in the pediatric population presented in the literature [33–36] in distribution of participants into age subgroups. In our opinion, such an analysis of the PWV values increases the correctness and statistical significance of the obtained results.

We found that the PWV values of children of the main group at the age of 5–7 years do not differ from those of the control group. In the 8–12-year-old subgroup in patients with FH, only the maximum PWV indicators were statistically significantly higher than in the comparison group. The identified deviations probably reflect the initial changes in the stiffness of the vascular wall in children of the main group. The most pronounced differences in the studied parameters were observed in children with FH in the age subgroup of 13–17 years old and were characterized by a statistically significant increase in PWVmin, mean PWV and PWmax relatively to the control group.

In our study, we also analyzed the dynamics of PWV growth depending on age. It was shown that PWV values increase with the age of the child both in familial hypercholesterolemia and in healthy children. This indicates that the studied indicators cannot be the same for all children and it is necessary to use age reference values in pediatrics. In addition, the increase in all three values of PWV was most pronounced in the group of 13–17 year old patients with FH, it allows us to suggest that they have a more pronounced change of properties of the vascular wall already at preclinical stages than in individuals with normal blood lipid profile.

A number of studies have revealed an increased PWV in children with hypertension [37], increased body mass index [38, 39]. In the present study, special attention was paid to patients with FH without risk factors such as smoking, obesity, and high blood pressure. Thus, the authors were able to assess the effect of hypercholesterolemia on the change in PWV precisely. The established correlation between total cholesterol level and PWV values allows us to regard an increase in total cholesterol level as a leading factor in forming the arterial stiffness in children with FH. In addition, the registration of the initial changes in PWV in the group with FH from 8–12 years old with further progression of the process in the absence of such changes in children 5–7 years old indicates a possible cumulative effect of cholesterol and its effect on the artery wall condition. This is consistent with large randomized studies showing that the effect of LDL on the development of atherosclerotic vascular disease is determined not only by the absolute level of LDL, but also by its cumulative effect on target organs [2, 40, 41].

#### **7. Conclusion**

Thus, the relationship between cholesterol level, age, and arterial stiffness indicators in familial hypercholesterolemia makes it possible to recommend the study of pulse wave velocity as a possible additional method for studying the cardiovascular risk in children with familial hypercholesterolemia and assessing the progression of the disease

### **Conflict of interest**

Authors declare no conflict of interest.
