Dissertation committee:
Δημήτριος Γουργιώτης, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαρία Τσολιά, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ευθυμία Αλεξοπούλου, Καθηγήτρια, Ιατρική Σχολή,ΕΚΠΑ
Αναστασία Γαρούφη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Αχιλλέας Αττιλάκος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αλεξάνδρα Σολδάτου, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Μαριέττα Χαρακίδα, Λέκτορας, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Introduction: Atherosclerosis begins in childhood and manifests itself in adulthood. Early detection is important to prevent or delay the onset of cardiovascular disease. The most widely used non-invasive method for the assessment of atherosclerosis is the measurement of the intima media thickness in the common carotid artery (cIMT). The cIMT measurement is a simple, inexpensive, and reproducible method for assessing and monitoring children and adolescents who are at increased risk for early atherosclerotic disease such as those with dyslipidemia.
Objectives: The aim of the study was to evaluate cIMT with the help of B-mode ultrasound in children and adolescents with dyslipidemia and other chronic diseases and its correlation with body mass index, the underlying disease and its treatment.
Material and Methods: The study population consists of 1626 children and adolescents (825 males), aged 4 - 18.3 years, 1149 with dyslipidemia, 286 with normal lipid profile (controls), 27 with familial hypercholesterolemia treated with atorvastatin, 33 adolescents with polycystic ovary syndrome (PCOS), 50 with chronic kidney disease (CKD)and 77 with neoplastic disease. cIMT was measured at 6 points on each side in all participants and the mean of the measurements was calculated by the manual method. Moreover, an individual and family history was obtained and a detailed clinical examination was performed. A fasting lipid profile, markers of renal, hepatic and thyroid function, and a complete blood count were assessed. In children with CKD, a more extensive monitoring of renal function was performed and adolescents with PCOS were evaluated for insulin resistance. Children who were on medication were evaluated before and after treatment.
Results: The results of the study by population group are as follows:
1st) Group of individuals with and without dyslipidemia: Mean and median cIMT did not differ significantly between the two groups, even in the same sex. Age and gender were important independent predictors of cIMT in both groups. The older the age the higher cIMT, while girls had significantly lower cIMT than boys, regardless of age and BMI. BMI was a significant independent predictor only in the group with dyslipidemia. Obese children had significantly higher cIMT compared to normal weight and overweight ones. Tanner's pubertal stage, after correction for confounding factors, did not affect cIMT. In the dyslipidemia group, cIMT was significantly correlated with LDL ≥190 mg / dl, Non-HDL, ApoB, and atherosclerotic markers LDL / HDL & ApoB / ApoA1 (multifactorial analysis). 42.4% of subjects with dyslipidemia had also elevated Lp (a) (≥ 30 mg / L), which did not affect cIMT, even when the cutoff was ≥100 mg / dl. A positive family history of dyslipidemia and early cardiovascular disease was an important predictor of pediatric cIMT.
2nd) Dyslipidemia group treated with atorvastatin: Males showed a tendency to decrease cIMT after 7-35 months of administration, although in 65% of them the LDL-C reduction target (<130 mg / dl) was not achieved. The cIMT before treatment was significantly higher than that of males of similar age with a normal lipid profile. Males had significantly higher cIMT than females.
3rd) Group of adolescents with PCOS: The cIMT was no different from the cIMT of adolescents, of similar age and Tanner stage, without PCOS. Systolic blood pressure and BMI z-score had a significant positive correlation with cIMT.
4th) Group of individuals with CKD: Among the 50 participants, 11 were on dialysis and 16 were renal transplant recipients. The cIMT of CKD patients was significantly higher than that of the 50 sex- and age-matched healthy controls and had a significant positive correlation with the waist-to-height (PM / Height) ratio. In the patient group, elevated creatinine levels were a significant independent predictor of cIMT.
5th) Group of participants with neoplastic disease: the cIMT did not differ significantly to sex- and age-matched controls. In the total population (patients and controls), boys had significantly higher cIMT compared to girls, while their age did not differ significantly. The age had a significant correlation with cIMT only in boys.
Conclusions: The absence of a significant difference in cIMT of children and adolescents with dyslipidemia or neoplastic disease and of adolescents with PCOS from healthy children and adolescents with normal lipid profiles indicates that appropriate intervention may delay or prevent the progression of atherosclerotic disease. Age and gender are the most important predictors of cIMT. Obese children with dyslipidemia have a significantly higher cIMT than leptosomes. Only very high levels of LDL appear to affect cIMT. A positive family history of dyslipidemia and early cardiovascular disease is an important predictor of cIMT in the pediatric population. Atorvastatin treatment appears to reduce the rate of cIMT progression in boys with familial hypercholesterolemia. Patients with CKD, including transplant recipients, are at increased risk of early atherosclerosis, as they have significantly higher cIMT compared to controls. In addition, a significant effect on the increase of cIMT has the abdominal fat distribution, as estimated by the ratio of PM / Height, as well as the degree of renal impairment.
Keywords:
Carotid intima-media thickness, Atorvastatin, Dyslipidemia, Polycystic ovarian syndrome, Chronic kidney disease, Neoplastic disease, Children
