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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 2  |  Issue : 4  |  Page : 201-205

The status of vascular wall in children and adolescents with metabolic syndrome


1 Department of Children Diseases Propaedeutics, Children Endocrinology and Diabetology, Saratov State Medical University, n.a. V.I. Razumovsky, Saratov 410012, Russia
2 Department of Foreign Languages, Saratov State Medical University, n.a. V.I. Razumovsky, Saratov 410012, Russia

Date of Submission24-Feb-2015
Date of Decision25-Sep-2015
Date of Acceptance17-Oct-2015
Date of Web Publication2-Dec-2015

Correspondence Address:
Nina Victorovna Posokhova
Department of Children Diseases Propaedeutics, Children Endocrinology and Diabetology, Saratov State Medical University n.a. V.I. Razumovsky, Saratov
Russia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2347-9906.170907

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  Abstract 

Introduction: Global epidemic of type 2 diabetes mellitus and metabolic syndrome (MS) has precipitated a growing interest in the structural-functional changes in blood vessels of children and young adolescents. Subjects and Methods: The study was carried out in 45 children with MS, a comparative group of 25 with only primary obesity and 20 without obesity. The lipid levels were estimated along with a test for insulin resistance by standard methods. The daily monitoring of blood pressure (BP), electrocardiogram, and status of the vascular wall were assessed with automated instrumentation. The pulse rate velocity in aorta, BP, arterial rigidity index and other indices were correlated in all the three groups. Results: In children with MS, there was the demonstrable rigidity of vascular wall; it was 3.5 times more than in children with primary obesity. There was a high correlation of arterial hypertension with body mass index and other features of MS. Conclusion: The data suggests there is a need to conduct long-term interventional studies to intervene reversal of vascular changes.

Keywords: Arterial hypertension, metabolic syndrome, vascular changes


How to cite this article:
Bolotova NV, Posokhova NV, Dronova EG, Chernyshkova EV. The status of vascular wall in children and adolescents with metabolic syndrome. J Obes Metab Res 2015;2:201-5

How to cite this URL:
Bolotova NV, Posokhova NV, Dronova EG, Chernyshkova EV. The status of vascular wall in children and adolescents with metabolic syndrome. J Obes Metab Res [serial online] 2015 [cited 2019 Jul 19];2:201-5. Available from: http://www.jomrjournal.org/text.asp?2015/2/4/201/170907


  Introduction Top


According to modern viewpoint, the term "metabolic syndrome" (MS) refers to symptom-complex, which is characterized by obesity of the central type, arterial hypertension (AH), hyperglycemia, a decrease in the concentration of high-density lipoproteins (HDLP), an increase of triglyceride (TG) concentrations in serum (the International Diabetes Federation, 2007). Being a part of MS, AH mediates its effects by damage to structure and function of arteries. Experts from World Health Organization have described MS as "the pandemic of the 21st century."[1],[2] The data of different authors, describe the prevalence of MS in the world, ranging from 4% to 28.7%. The incidence of MS has acquired a nature of an epidemic, primarily due to the high prevalence of obesity.[3]

At present, there is a growing interest in studying the structural-functional changes in blood vessels of children and adolescents with MS, by means of exact, noninvasive methods. Such an understanding of the vascular lesions in these patients may form a prerequisite for the prevention and early medical correction of AH.

The research objective of the present study was to evaluate the status of the vascular wall in children and adolescents with MS and correlate the same with other variables.


  Subjects and Methods Top


Ninety obese children, aged 11–16 years were screened with clinical and laboratory methods. Forty-five were diagnosed to have MS. The comparative group consisted of 25 children with primary obesity, but no MS. The control group included 20 healthy children without obesity.

The criteria for MS diagnosis were based on the guidelines proposed by the International Diabetes Federation in 2007.[4]

The evaluation included the history of complaints, family history, and a personal history. The physical development was assessed by height, weight, body mass index (BMI), standard deviation score BMI (SDSBMI), waist circumference (WC), and sexual development by Tanner's classification. A general and systemic physical examination was carried out.

The lipid metabolism was studied by the levels of serum cholesterol TG, HDLP and low-density lipoproteins (LDLP). Carbohydrate metabolism was assessed by fasting plasma glucose (FPG) level by biochemical analyzer Stat Fax 1904 Plus, Awareness Technology (USA). The serum level of immunoreactive insulin (IRI) was determined by immunoenzyme analysis with Multiskan Ex apparatus (Thermo Elektron, Finland), HOMA-index was calculated by the standard formula: HOMA = (IRI0 × Gl0)/22. Five wherein IRI0 is the concentration of IRI in fasting blood serum, in mcU/ml, and Gl0 is FPG in mmol/l.

The blood pressure (BP) was assessed by the results of daily monitoring of BP (DMBP) and electrocardiogram (ECG) using "Kardiotekhnika–4000 AD" system ("INKART," Saint-Petersburg, Russia). The width of the cuff was selected in accordance with the arm circumference and standard recommendations. This apparatus is an automatic, programmable monitor for BP, ECG, and heart rate measurements based on oscillometric principle.

The status of the vascular wall was evaluated by the method of volumetric steganography by means of PO BPLab Vasotens device ("Pyotr Telegin" Ltd., Russia). All values were calculated automatically and the most significant variables characterizing elasticity of blood vessels were used in the present study: (1) Pulse wave velocity in aorta, determined by certain time of reflected wave distribution, (2) arterial rigidity index, (3) index augmentation in aorta-Alx and Alx0-indicate which, first of all, characterizes intensity of the reflected wave and its contribution to the increase of pulse BP, and + (4) maximum speed of BP increasing.(dP/dt) max.

Statistical calculations were performed with the use of the statistical program XL Statistics, version 4.0 (Rodney Carr, Australia, 1998). The data with normal distribution are presented as the median and as 1–3 quartiles. For comparison of the groups with normally distributed parameters, Student's t-test was used. Evaluation of statistically significant differences between the compared groups with incorrect distribution was carried out using the nonparametrical U-test of Mann–Whitney. Differences between the parameters under study were recognized as valid at the level of statistical significance of P < 0.05. Correlative analysis with calculation of correlation coefficient by Pearson was used to assess the relationship between separate indices.


  Results Top


During the period of the survey, the children occasionally complained of headaches, fatigue, weakness, and shortness of breath during physical activity. These complaints were of a transient and mild in nature.

The family history of obesity was revealed in 75% of children. AH was present in 85% of children. Diabetes mellitus of type 2 was present in 25% of children. There was a history of close relatives with obesity and AH in 35% of children.

The BMI of children and adolescents with obesity exceeded 95 percentile, and its median was 2823–35 kg/m 2 index of SDSBMI of 2.9 (2.75–3.5), WC ranged within 9489–110 cm. BMI of the comparative group was 22 (19–27) kg/m 2, SDSBMI of 2.2 (1.9–2.8); the mean value of WC was 90.5 (85–96) cm. Almost all the children showed early sexual maturation. By 14–15 years they had reached the IV th–V th stage of puberty as per Tanner's classification.

According to the guidelines of MS with three components (abdominal obesity [AO], insulin resistance [IR], hypertriglyceridemia [HT] was present in 11% of patients; MS with four components [AO], IR, HT, reduced HDLP) was present in 33%. With five components of MS (AO, IR, HT, reduced HDLP and AH) 56% of patients had MS.

The following changes were revealed: In lipids-hypercholesterolemia – in 70% of children, increase in TG level in 35% of patients, raised LDLP in 15% of surveyed and reduced HDLP level in 40% of cases. Peripheral IR, as characterized by increasing level of basal insulin of blood, and HOMA index were present in 65% of patients [Table 1]. Besides, the presence of straight of medium correlation between pulse wary velocity (PWV) and IRI, decreased HDLP and HOMA index was revealed (r = 0.6).
Table 1: Markers of lipid and carbohydrate metabolism in children and adolescents with obesity

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DMBP showed that in 55% of children with MS had AH. In 15 children, BP was stable. Ten patients had isolated systolic hypertension. The maximum and minimum daily average indices of systolic BP (SBP) and diastolic BP (DBP), index of hypertension and index of hypotension in the group of children with primary obesity were significantly lower in comparison with persons with MS and did not go beyond 95 percentile for the corresponding height and sex. The daily index of SBP in patients with primary obesity was high in 50% case and comprised of arise of 19% (15–23), for the other half of patients of this group the values were optimal. The daily index of DBP, in 40% of patients, was reduced insufficiently by 18% (15–21). Thus, in children of comparative group circadian profile of BP was characterized by desynchronization of daily BP rhythms (mainly "nondippers" according to SBP and DBP at night).

AH in children with MS is characterized by maximum indices of both SBP and DBP during the day. The increase in hypertension and hypotension indices, the increase in the speed of SBP and DBP morning rise, characterize the changes of SBP daily profile by the type of "nondippers," in 60% of children. Moreover, in 20% – by the type of "night-peaker." The daily profile of DBP was normal in most of the cases and only in 20% of surveyed children a monophasic circadian profile was revealed ("nondipper" group) [Table 2].
Table 2: Indices of DMBP in children and adolescents with obesity

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In our results, a straight and strong correlation was shown between SDSBMI and PWV, ASI, Alx0 (r = 0.7). With increasing obesity, the rise in PWV as well as in the index of arterial rigidity and the index of aortic augmentation were marked [Table 3].
Table 3: Indices of vascular wall rigidity in children and adolescents with obesity

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  Discussion Top


Sufficient data have shown the importance of determination of arterial wall rigidity as an indicator of vascular remodeling, during the last decade.[5],[6] The factor responsible for the pathological processes in vascular wall is primarily the disturbance of the endothelial cell function. An imbalance between mediators of vasodilatation and vasoconstriction tends to increase the vascular tonus. Long-term endothelial imbalance leads to hypertrophy and hyperplasia of smooth muscle cells (SMCs) of the vascular wall. This leads to disturbances of vascular elastic properties. An increase in the SMC mass enhances further the degree of spasm in response to vasoconstrictors. This leads to an increase in the peripheral vascular resistance and contributes to the fixity and aggravation of AH.[6]

Vascular endothelium plays an important role in genesis and development of hypertension, especially in the presence of IR. The endothelium is the main target organ in MS. With IR the release of vasoconstrictors (thromboxane A2, prostaglandin F2, endothelin 1) increases and the release of vasodilators (nitric oxide) decrease.[7] Recent studies show that the rise of aortic rigidity, measured by the degree of increase in pulse wave velocity, is an independent risk predictor of cardiovascular complications. PWV is a parameter that integrates geometry and elastic properties of vessels. It is calculated by Moins–Korteweg equation, and it follows that PWV increases with the growth of rigidity and thickness of a vessel wall.

Children's obesity is considered to be a serious socially significant problem, which leads to increase of cardiovascular diseases and a risk of early mortality. Obesity is associated with MS, and one of its components is AH.[8] The occurrence of AH is connected with increased activity of the sympathetic nervous system, hyperinsulinemia, IR, as well as disturbances in the vascular wall elasticity. There is a paucity of data on the prevalence of MS in childhood and adolescence and about its effect on the cardiovascular system and the changes in the vascular wall. The sporadic studies on MS in children and teenagers are difficult to interpret as the clinical diagnostic criteria of MS in this age group have not been finally recognized. Early detection and opportune treatment of AH in children and adolescents with obesity can contribute to a reduction in morbidity and mortality from the future cardiovascular diseases.

In recent years, the opportunity to study the condition of vascular tonus by using noninvasive methods has increased. PWV and augmentation index, rigidity index of arteries are interesting from the viewpoint of pathophysiology and have a great prognostic value. In 2007, the European Congress on AH gave recommendations for measuring PWV, augmentation index, rigidity index of arteries in routine medical practice along with such "standard" tests for assessment of cardiovascular system status as echocardiography, 24 h BP measurement, etc.[9]

Pulse wave velocity is an independent predictor of coronary heart disease (CHD) and stroke even in apparently healthy people. Such was a conclusion of the researchers who have been working for Rotterdam study and who have examined 2835 practically healthy people. This study has revealed an increase in the risk of cardiovascular diseases due to the growth of PWV index.[10] Thus, a study of a large cohort of out-patient cases of AH, under medical supervision in the period of 16 years, had revealed a direct correlation between the level of arterial stiffness and rate of mortality from cardiovascular pathology.[11] According to the research of Asmar et al., a reduction of ductility and an increase of arterial stiffness have been marked during the course of CHD and AH.[12] Some authors regard the increase of PWV as a sign of subclinical coronary atherosclerosis and consider it reasonable to use this sign (biomarker) as an independent risk factor of AH. Hence, it is necessary to detect this marker in patients with an asymptomatic course of the disease.[13] However, the nature of the relationship of linear blood flow and PWV with an increased endothelial dysfunction and raised BP in the large arteries is still unclear. There are scarce publications on this topic available in the literature.

The research on the determinants of atherosclerosis in young people (PDAY STUDY) was carried out in a multicenter cooperative study and coupled with study of the autopsy materials from 3000 persons aged 15–34, who had died in accidents. It was revealed that the degree of atherosclerotic changes in coronary arteries in this group directly correlated with dyslipidemia, AH, obesity, and increased glucose level.[14]

Japanese researchers have demonstrated the good reproducibility of noninvasive methods to define PWV in the central and peripheral arteries. There was a high degree of correlation between the noninvasive indices and those obtained by the invasive method.[15] The thickening of the vascular wall in the presence of MS in adolescents was correlated with the rise in PWV spread. This was shown as an evidence of increasing of vascular rigidity. This is one of the most significant predictors of cardiovascular risk in childhood and adolescence.[16] Our study has also shown that an early assessment of vascular function in children with MS, by noninvasive methods is desirable, so as to prevent the future risks. There is a need to conduct interventional studies, with lifestyle and drugs, in children with MS and vascular changes to assess the degree of reversal in AH with metabolic improvement, weight loss and a control of dyslipidemia.


  Conclusions Top


Thus, the prevalence of MS in children with obesity was 65%, and the frequency of its occurrence was on a steady rise due to increase in obesity. MS with three components was diagnosed in 11% of patients; with four components – in 33% and with five components – in 56% of patients. In children with MS, there is the rigidity of vascular wall, which is 3.5 times more often identified than in children with simple obesity. In 70% of children with MS artery rigidity and thickness of vascular wall are increased, determined by PWV spreading. The latter is the predictor of AH and has a high correlation with SDSBMI and with various components of MS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
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2.
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Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, et al. For the ASCOT investigators prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required as atenolol adding bendroflumethiazide as required, in the ASCOT-BPLA: A multicenter randomised controlled trial. Lancet 2005;366:895-906.  Back to cited text no. 6
    
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Ginzburg MM, Kryukov NN. Effect on the development of metabolic syndrome. Prevention and treatment. Moscow: Medpraktika; 2002.  Back to cited text no. 7
    
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Roshchupkin AN. Changing the cardiovascular system in children with metabolic syndrome. Actual issues of diagnostics Pharmacotherapy 2012;154:8-12.  Back to cited text no. 8
    
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Steinberger J, Daniels SR. Obesity, insulin resistance, diabetes and cardiovascular risk in children: An American Heart Association scientific statement from the Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young) and the Diabetes Committee (Council on Nutrition, Physical Activity, and Metabolism). Circulation 2003;107:1448-53.  Back to cited text no. 9
    
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O'Rourke MF, Pauca AL. Augmentation of the aortic and central arterial pressure waveform. Blood Press Monit 2004;9:179-85.  Back to cited text no. 10
    
11.
Mitchell GF, Parise H, Benjamin EJ, Larson MG, Keyes MJ, Vita JA, et al. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: The Framingham Heart Study. Hypertension 2004;43:1239-45.  Back to cited text no. 11
    
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Asmar RG, London GM, O'Rourke ME, Safar ME; REASON Project Coordinators and Investigators. Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: A comparison with atenolol. Hypertension 2001;38:922-6.  Back to cited text no. 12
    
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Kavey RE, Allada V, Daniels SR, Hayman LL, McCrindle BW, Newburger JW, et al. Cardiovascular risk reduction in high-risk pediatric patients: A scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: Endorsed by the American Academy of Pediatrics. Circulation 2006;114:2710-38.  Back to cited text no. 13
    
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McGill HC Jr, McMahan CA, Gidding SS. Preventing heart disease in the 21st century: Implications of the pathobiological determinants of atherosclerosis in youth (PDAY) study. Circulation 2008;117:1216-27.  Back to cited text no. 14
    
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Hirata K, Kawakami M, O'Rourke MF. Pulse wave analysis and pulse wave velocity: A review of blood pressure interpretation 100 years after Korotkov. Circ J 2006;70:1231-9.  Back to cited text no. 15
    
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