Study of atheromatosis markers in healthy children and adolescents in Attica: specific markers for the prevention of atheromatosis: atheromatosis risk in children

IntroductionThe atherosclerotic process is a chronic inflammatory disease that begins in childhood, develops during adolescence and is manifested by some of its complications in adulthood. The establishment, extent and progression of atherosclerotic lesions are dependent on many genetic and environmental factors, such as dyslipidemias (primary or secondary), obesity, hypertension and chronic inflammation. Many of these factors are transferred from childhood to adolescence and adulthood. The effective prevention and treatment of risk factors, reduces the risk of early atherosclerotic and future cardiovascular disease. Purpose of the StudyThe study is epidemiological and aims at detecting a number of risk factors for early atherosclerotic disease in a healthy population, as part of a screening test.Materials and MethodsThe study included 688 healthy children and adolescents, 382 males (55.5%) and 306 females (44.5%), aged 3.6 to 16.8 years, residents of Attica, Greece. Somatometric data was recorded from all the children and the BMI was calculated. For the classification in normal BMI, overweight and obese, the international growth curves were applied. The levels of lipids, lipoproteins, apolipoproteins and high sensitivity C-reactive protein were determined, in morning fasting blood. Peptide hormones, brain natriuretic peptide (BNP), adiponectin (ADP) and urotensin II (U-II) were identified in fasting plasma, in some of the study population. LDL-C levels were directly measured by a homogeneous method and calculated using the Friedewald and Anandaraja formulas. The risk of atherosclerosis was estimated based on the high levels of LDL-C and non-HDL-C. The levels of directly measured LDL-C were compared to those calculated by the above formulas, for the diagnosis of hypercholesterolemia in the above population. In addition, the above levels were compared in a group of 312 children and adolescents with known hypercholesterolemia. For the statistical analysis of the results, the statistical package STATA for windows v8.5 was used (StataCorp, Texas, USA, 2006). P <0.05 was considered statistical significant.ResultsThe 33% of children and adolescents, 36% of males and 28.7% of females had increased BMI (overweight 25.6%, obese 7.1%). Obesity was more common in boys (10.2% vs. 3.2%). Excessive weight was more common in adolescence (37.9%) compared to pre-puberty (29.4%).In all children, 50th percentile for TC, TGs, LDL-, HDL- and non-HDL-cholesterol was 161mg/dl, 49mg/dl, 93mg/dl, 60mg/dl and 104mg/dl respectively, while the levels corresponding to 75th percentile were 180mg/dl, 64mg/dl, 108mg/dl, 69mg/dl and 119mg/dl, respectively. Levels of apolipoproteins A and B and lipoprotein (a) 161mg/dl, 73mg/dl and 7mg/dl corresponded to 50th percentile, while levels of 175mg/dl, 82mg/dl and 15.4mg/dl corresponded to 75th percentile. Girls had higher levels of LDL-C and non-HDL-C than boys, but the difference was not statistically significant. In addition, the mean levels of TC, LDL-C, HDL-C and Non-HDL-C were significantly lower and mean levels of TGs significantly higher in adolescents compared to pre-pubertal males alone. Obese children had significantly higher levels of TGs, LDL-C, non-HDL-C and apo-B and significantly lower levels of HDL-C and apo-A1 compared to both normal weight and overweight groups. Overweight children were different from those with normal weight only to the TGs, HDL-C and apo-A1 levels.The 22.7% of all children had "undesirable" LDL-C levels, with 15% having "marginally elevated" and 7.7% being "high". Non-HDL-C levels were "undesirable" at 21.7% (15.3%: "marginally elevated" & 6.4%: "high"). According to the above, there appears to be no difference in estimating the risk of atherosclerosis no matter if LDL-C or non-HDL-C levels are used. In contrast, the comparison of the above indicators in the group with known hypercholesterolemia showed that the directly measured LDL-C is the most reliable indicator for the determination of risk compared to non-HDL-C. Using non-HDL-C, 16% of those with hypercholesterolemia escape the diagnosis, while in 13% of those with LDL ≥ 160 mg/dl the levels are underestimated.The Friedewald formula, compared to direct measurement, underestimates the levels of LDL-C, with the difference being significant only in the group of children with dyslipidemia. The Friedewald formula had a better correlation with the direct measurement of LDL-C and less dispersal, compared to the Anandaraja formula. In the dyslipidemic group, using Anandaraja had the risk of overestimating LDL-C levels and a higher number of children being eligible for medication.The mean levels of hsCRP in screen tested healthy children were 1.51 (± 4.01) mg/L, while the 50th and75th percentiles corresponded to levels of 0.43 and 1.11 mg/L respectively. No correlation with lipid-lipoprotein levels was found. As expected, obese children had higher levels compared to normal BMI children.From the statistical analysis of BNP, ADP and U-II levels to a part of the study population, no significant correlations with sex, age, and BMI were found. Furthermore, levels of BNP and ADP were not correlated with lipid-lipoprotein levels, whereas U-II had a strong correlation with HDL-C and apoA1 levels.ConclusionsA significant number of healthy children and adolescents are overweight or obese. In addition, a significant number has "undesirable" levels of LDL-C and non-HDL-C. In contrast, lipoprotein (a) levels do not appear to constitute a risk factor for atherosclerosis in this population. Increased weight was associated with a more unfavorable lipidemic profile and higher levels of hsCRP. The percentages of children with "undesirable" levels of directly measured LDL-C did not differ significantly from those with "undesirable" levels of non-HDL-C. The Friedewald equation, despite its limitations, is sufficient as a tool for the screening of hypercholesterolemia in the pediatric population. The Anandaraja’s formula is not suitable for screening, because it gives many false positive results as well as for diagnosing and monitoring children with hypercholesterolaemia, because it involves the risk of overestimation and over-treatment.ΕισαγωγήΗ αθηρωματική διεργασία είναι μια χρόνια φλεγμονώδης νόσος που αρχίζει στην παιδική ηλικία, εξελίσσεται κατά την εφηβεία και εκδηλώνεται με κάποια από τις επιπλοκές της στην ενήλικη ζωή. Η εγκατάσταση, η έκταση και η εξέλιξη των αθηρωματικών βλαβών εξαρτάται από πολλούς γενετικούς και περιβαλλοντικούς παράγοντες, όπως είναι οι δυσλιπιδαιμίες (πρωτοπαθείς ή δευτεροπαθείς), η παχυσαρκία, η υπέρταση και η χρόνια φλεγμονή. Πολλοί από αυτούς τους παράγοντες περνούν από την παιδική, στην εφηβική και στην ενήλικη ζωή. Η αποτελεσματική πρόληψη και αντιμετώπιση των παραγόντων κινδύνου μειώνει τον κίνδυνο πρώιμης αθηρωματικής και μελλοντικής καρδιαγγειακής νόσου. Σκοπός της μελέτης Η μελέτη είναι επιδημιολογική και έχει σαν στόχο την ανίχνευση ενός αριθμού παραγόντων κινδύνου πρώιμης αθηρωματικής νόσου σε μια υγιή πληθυσμιακή ομάδα, στα πλαίσια ενός προληπτικού ελέγχου. Υλικό και ΜεθοδολογίαΗ μελέτη περιέλαβε 688 υγιή παιδιά και εφήβους, 382 άρρενες (55,5%) και 306 θήλεα (44,5%), ηλικίας 3,6 έως 16,8 χρόνων, κατοίκους Αττικής. Σε όλα τα παιδιά καταγράφηκαν τα σωματομετρικά στοιχεία και υπολογίστηκε ο ΒΜΙ. Για την ταξινόμηση σε φυσιολογικού ΒΜΙ, υπέρβαρα και παχύσαρκα χρησιμοποιήθηκαν οι διεθνείς καμπύλες αύξησης. Σε πρωινό αίμα νηστείας προσδιορίστηκαν τα επίπεδα των λιπιδίων, λιποπρωτεϊνών, απολιποπρωτεϊνών και της υψηλής ευαισθησίας C-αντιδρώσας πρωτεΐνης. Σε μέρος του πληθυσμού της μελέτης προσδιορίστηκαν σε πλάσμα νηστείας οι πεπτιδικές ορμόνες, εγκεφαλικό νατριουρητικό πεπτίδιο (ΒΝΡ), αδιπονεκτίνη (ADP) και ουροτενσίνη ΙΙ (U-II). Τα επίπεδα της LDL-C μετρήθηκαν άμεσα με ομοιογενή μέθοδο και υπολογίστηκαν με τις φόρμουλες Friedewald και Anandaraja. Ο κίνδυνος αθηρωμάτωσης εκτιμήθηκε με βάση τα υψηλά επίπεδα της LDL-C και της non-HDL-C. Τα επίπεδα της άμεσα μετρούμενης LDL-C συγκρίθηκαν με αυτά των υπολογιζόμενων με τις παραπάνω φόρμουλες για τη διάγνωση της υπερχοληστερολαιμίας στον παραπάνω πληθυσμό. Επιπλέον, συγκρίθηκαν σε ομάδα 312 παιδιών και εφήβων με γνωστή υπερχοληστερολαιμία. Για τη στατιστική ανάλυση των αποτελεσμάτων χρησιμοποιήθηκε το στατιστικό πακέτο STATA for windows v8.5 (StataCorp, Texas, USA, 2006). Σημαντικό θεωρήθηκε P