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Background  Early vascular alteration, atherosclerosis and coronary artery disease have emerged as important cardiovascular complications among beta-thalassemia major (B-TM) patients. The aims of the current study were to assess the prevalence of premature atherosclerosis among our B-TM patients, and to investigate the diagnostic value of serum Osteoprotegerin assay as an early biomarker for atherosclerosis.    Methods  This cross-sectional study was conducted at Hematology unit - Pediatric Department, Zagazig University Children Hospital- Egypt in the period from March 2014 to March 2015. A total of 115 children were enrolled in the current study; as sixty-five (65) children with beta thalassemia major aged 5–18 years, on regular blood transfusion regimen represented the patient group. While fifty (50) healthy children, with comparable age and gender, were assigned as control group. All participants were subjected to history taking, thorough clinical examination and laboratory investigations including; complete blood count, liver and kidney function tests, C- reactive protein, lipid profile, serum ferritin and serum Osteoprotegerin (OPG) assay. Also, carotid artery intima media thickness (CAIMT) was performed by duplex ultrasound for patients and controls.    Results  Our B-TM patients were transfusion-dependent for as long as 8.5 ± 3.8 years with significantly higher serum ferritin levels (2490 ± 1579 ng/dl vs 83 ± 32 ng/dl,  p  = 0.001), C-reactive protein (5.7 ± 5.7 vs 0.9 ± 0.9), liver enzymes and bilirubin when compared to controls. Significantly higher serum triglyceride (128 ± 20 vs 101 ± 7 mg/dL,  p  = 0.009) and atherogenic index of plasma (0.45 ± 0.12 vs 0.22 ± 0.04,  p  = 0.001) were recorded in patients than comparisons. On the contrary, total serum cholesterol (116 ± 16 vs 143 ± 5,  p  < 0.001), low density lipoprotein-cholesterol (LDL-C) (44 ± 9 vs 73 ± 6,  p  < 0.001) and high density lipoprotein cholesterol (HDL-C) (39 ± 2 vs 61 ± 5,  p  < 0.001), were significantly lowered in patients versus normal peers. Carotid arteries intima media thickness (CAIMT) of both side were significantly increased for patients (Rt 0.62 ± 0.2 vs. 0.29 ± 0.07 mm,  p  = 0.001 & Lt 0.66 ± 0.17 vs 0.29 ± 0.05 mm,  p  = 0.001) when compared with healthy controls, and showed positive correlation with, serum triglyceride, atherogenic index of plasma, and serum Osteoprotegerin levels. ELISA assay of serum Osteoprotegerin (OPG) revealed significantly higher levels for thalassemia patients than matched healthy controls (427 ± 102 vs. 324 ± 126 pg/ml,  p  = 0.02). Of particular interest is the obvious positive correlation between OPG levels and CAIMT of both sides (Rt r 0.54,  p  = 0.001 &Lt r 0.479,  p  = 0.001) and also with serum triglycerides (r 0.374,  p  = 0.03).    Conclusions  Subclinical atherosclerosis started prematurely in children with beta- thalassemia. Carotid artery intima media thickness represented a simple, accurate and non-invasivemodality for early detection ofatherosclerosis. It was correlated well with serum Osteoprotegerin; this finding highlighted the possible validity of OPG assay as an early predictor of atherosclerosis in thalassemia children.

Premature atherosclerosis in children with beta-thalassemia major: New diagnostic marker