Elsevier

Atherosclerosis

Volume 167, Issue 2, April 2003, Pages 275-286
Atherosclerosis

New atherosclerosis risk factors in obese, hypertensive and diabetic children and adolescents

https://doi.org/10.1016/S0021-9150(03)00003-0Get rights and content

Abstract

In the last few years it has been proved that risk factors for atherosclerosis are present in children and adolescents, and that already at this early age they are connected with anatomic, atheromatous changes in vessels. These changes can not be fully explained as occurring in young people exhibiting traditional risk factors for the disease. The aim of the study was to evaluate levels of several new atherosclerosis risk factors (lipoprotein (a) (Lp(a)), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), homocysteine (Hcy), fibrinogen (FB), tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor type 1 (PAI-1)) in children and adolescents with traditional risk factors (obesity, hypertension, diabetes). Materials and methods: The study group consisted of 285 children and adolescents aged 14.3 years. Children were divided according to their main disease into groups: group A, children with obesity (n=49); group B, children with obesity and coexisting hypertension (n=56); group C, children with hypertension (n=58) and group D, children with diabetes (n=122). Control group consisted of 79 healthy children and adolescents aged 14.1 years. Lp(a), Apo A-I and Apo B levels were estimated by use of immunoturbidimetric methods; total Hcy, FB, t-PA and PAI-1 were estimated by use of immunoenzymatic methods. Results: Lp(a) level in the total study group was 30 mg/dl and was over twice higher than in control group, 14 mg/dl. Apo A-I level was significantly lower in group A (127.6 mg/dl) and in group B (125.8 mg/dl) versus 135.6 mg/dl in controls. The level of Apo B was significantly higher in total study group (86.2 mg/dl) and in groups A, B and D versus 73.5 mg/dl in controls. Hcy was higher in group B (8 μmol/l) and in group C (9.4 μmol/l) versus 6.2 μmol/l in the control group. The FB level was higher in the total study group (276.7 mg/dl) and in groups A (318.8 mg/dl) and B (322.6 mg/dl) versus 252.8 mg/dl in controls. Significantly higher t-PA level was found in groups A (9 ng/ml) and B (9.7 ng/ml) versus 7.3 ng/ml in controls, and PAI-1 level was significantly higher in the total study group (62.3 ng/ml) and in groups A (73.8 ng/ml), B (78 ng/ml) and C (73 ng/ml) versus 42.4 ng/ml in the control group. Correlation analysis showed significant relationship between body mass index (BMI) and Apo B, Hcy, FB, t-PA and PAI-1. Blood pressure values correlated positively with Hcy. Correlations were verified in multiple regression analysis models: FB and t-PA levels depended on BMI, and Hcy depended on systolic blood pressure. Conclusions: (1) Young obese, hypertensive and diabetic patients present significant disturbances in lipid metabolism, regarding mainly total cholesterol, LDL, triglycerides, as well as Lp(a), Apo A-I and Apo B levels. Unfavourable lipid profile is characteristic mainly for children with obesity and accompanying hypertension. (2) Elevated Hcy levels are found in children with hypertension. (3) Elevated FB level and diminished fibrinolytic activity are characteristic of obese children.

Introduction

During the last few years, it has been shown that risk factors for atherosclerosis appear during childhood and adolescence, and are already in that time associated with atherosclerotic changes in vessel walls [1]. This finding, along with the alarming rise in smoking, obesity and hypertension coupled with a decrease of physical activity in children and adolescents, sets a new task for public health, and encourages the development of methods of primary prevention within this age group [2], [3].

Identifying the risk factors for atherosclerosis for individual patients presents an important challenge for modern medicine. The prevention of atherosclerosis is a complex, holistic approach, which involves targeting numerous risk factors simultaneously. Searching for and discovering new risk factors is justified on the grounds that the discovery of traditional risk factors in a patient is not always a good indicator as to their predisposition toward developing atherosclerotic disease. About 25% of patients with coronary artery disease, particularly with premature onset, did not have any of the common, classical risk factors [4]. Numerous studies of proposed new risk factors in children show a correlation with a family history of cardiovascular disease. These studies usually focus on a selected single risk factor, and furthermore, are typically composed of only the healthy young population [5], [6]. Discovering and assessing new risk factors for atherosclerosis in children with recognised traditional risk factors may provide a new insight into the so far not fully understood mechanism of formation of atheromatous plaque, especially during the early first stages, when such changes are entirely reversible [7].

The aim of this work was to determine the concentrations of the routine parameters of lipid profile and metabolism in children and adolescents with obesity, hypertension and diabetes; to determine the concentrations of several new risk factors for atherosclerosis (lipoprotein (a) (Lp(a)), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), homocysteine (Hcy), fibrinogen (FB), tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor type 1 (PAI-1)), and to compare the selected groups with the purpose of characterising the type of anomalies in these new risk factors in young patients who carry more classical risk factors for atherosclerosis.

Section snippets

Materials

The study consisted of patients of the IInd Clinic for Children's Diseases of The Medical University of Bialystok, Poland and its related outpatient clinics for Diabetes, Cardiology and Endocrinology. In total, 285 (161 boys, 124 girls) children and adolescents were included, with the mean age being 14.3±3.3 years (age range 6–20). The group was divided according to their diagnosis. Group A (n=49) were obese children. Group B (n=56) were children diagnosed with obesity and coexisting

Patient selection

Obesity was diagnosed when the body mass index (BMI kg/m2), exceeded the 95th centile, matched according to age and sex (using the centile charts for the assessment of somatic development in children and adolescents issued by the Department concerning the physical development of children and adolescents, Institute of Mother and Child) [8]. Children with secondary obesity were not included in the study. High arterial blood pressure was diagnosed using 24-h ambulatory monitoring (ABPM), using the

Laboratory assessment of risk factors

For analysis 10 ml of blood was extracted from the left cubital vein, which was a morning sample taken before breakfast, after a 8–12 h overnight fast, and always taken secondarily when blood was to be taken for regular hospital purposes regarding diagnosis and treatment. To assess Lp(a), Apo B and Apo A-1, blood was taken for clotting, to assess Hcy with EDTA. To assess t-PA and PAI-1, plasma was used with citrate. Plasma and clot were frozen and kept at a temperature of −70 °C until analysis

Results

Serum concentration of cholesterol for all children studied was 166.3±33 mg/dl, and was significantly greater compared with that of the control group: 153.4±23 mg/dl (P<0.01). Significantly higher concentrations of total serum cholesterol were similarly observed for group A (165.5±34 mg/dl, P<0.05), B (168±31 mg/dl, P<0.01), and D (170.6±38 mg/dl, P<0.01). The concentration of LDL in all studied was 97.3±29 mg/dl and was significantly greater compared with that of the control group (89.7±23

Discussion

Evaluating the routine parameters of lipid metabolism showed higher concentrations of cholesterol and LDL in all the groups studied, except for hypertensive children. The highest concentrations of LDL were seen in obese children, and in obese, hypertensive children (group B). HDL levels were significantly lower in obese children groups. Triglyceride concentrations were significantly higher in all the groups studied, when compared with the control. The highest levels in triglyceride

Conclusions

  • 1.

    Young patients exhibiting obesity, hypertension and diabetes mellitus show significant abnormalities in lipid metabolism, particularly with reference to cholesterol, LDL-cholesterol, triglycerides, and the Lp(a), Apo A-I and Apo B. These abnormalities were most frequently seen in the group of obese children with accompanying hypertension.

  • 2.

    Elevated concentrations of Hcy appear in hypertensive children and in obese hypertensive children.

  • 3.

    Elevated concentrations of FB and decreased fibrinolytic

Acknowledgements

This work was supported by the State Committee for Scientific Research Grant No. 4 PO 5E 072 19.

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