An 11-year-old boy with familial hypercholesterolemia showing multiple xanthomas and advanced atherosclerosis, who responded to lipid-lowering therapy using statin.

Familial hypercholesterolemia (FH) is characterized by a high level of LDL-cholesterol (LDL-C) and a high prevalence of atherosclerotic coronary heart disease; however, hypercholesterolemia is usually the only clinical finding in children with heterozygous FH in their first decade of life. We report a case of FH in an 11-year-old boy who presented with multiple xanthomas at both elbows, thickened Achilles tendons, and hyperplasia of the intima-media complex of the carotid artery. Echocardiogram revealed partial calcification of the aortic and mitral valves, but no stenosis of the coronary arteries was detected on 3D-computed tomography. The activity of LDL receptors was reduced to 32% by lymphocyte assay. The family history showed vertical transmission of hypercholesterolemia from father to son, thereby suggesting dominant inheritance. After 12 months of treatment with statin and resin, his LDL-C decreased from 446 to 220 mg/dL, thickening of the Achilles tendons decreased from 1618 mm to 13 mm, and hyperplasia of the intima-media complex decreased from 1.3 mm to 0.7 mm. These findings suggest that our patient had heterozygous FH. However, based on his advanced atherosclerosis, we cannot exclude the possibility that our patient may be accompanying dyslipidemia due to causes in addition to heterozygous FH.

Relationship between lipid abnormalities and insulin resistance in Japanese school children.

OBJECTIVE: Dyslipidemia and insulin resistance (IR) are risk factors for coronary heart disease (CHD) in adults. To help prevent the development of CHD, it may be useful to understand the relationship between lipid abnormalities and IR during childhood. METHODS AND RESULTS: IR was assessed by the homeostasis model approximation index. We studied 1175 Japanese school children (642 boys and 533 girls), aged between 7 and 12 years. Obesity was defined by the body mass index standard deviation score (BMISD) (obese: BMISD > or = 2.0). BMISD was most significantly associated with IR in nonobese children (P=0.000). Associations of IR with lipid-related parameters were affected by BMISD. After being corrected by BMISD, in nonobese children, log triglycerides (TG), apoB and low-density lipoprotein (LDL) size in boys and log TG, LDL size, and high-density lipoprotein (HDL) cholesterol in girls were still significantly associated with IR (P=0.000 to 0.017). In obese children, all parameters except for LDL cholesterol in boys and LDL size in girls were significantly associated with IR (P=0.000 to 0.030). Multiple regression analysis showed that log TG and LDL size in nonobese children, log TG in obese boys and LDL size in obese girls were independently associated with IR. Children with IIb and IV hyperlipidemia had significantly higher IR than those with normolipidemia and IIa, even after correcting for BMISD and age. CONCLUSIONS: Our results suggest that in addition to controlling body weight, it may be important for school children to characterize lipid phenotypes to prevent progression to CHD and/or type 2 diabetes and to identify subjects who are at high risk for these disorders.

Serum C-reactive protein and its relation to cardiovascular risk factors and adipocytokines in Japanese children.

BACKGROUND: C-Reactive protein (CRP) is an independent risk factor for atherosclerotic coronary heart diseases (ACHD) in adults. To help prevent ACHD, it may be useful to understand risk factors during childhood. OBJECTIVE: The objective of this study was to investigate serum CRP and its relation to other risk factors for ACHD and adipocytokines (adiponectin, IL-6, and TNF-alpha) in Japanese children. METHODS: CRP, conventional risk factors for ACHD, and adipocytokines were determined in 568 children (340 boys and 228 girls, aged 7-10 yr). Serum concentrations of adipocytokines were measured by sandwich ELISA. RESULTS: Children with high CRP concentrations (highest tertile) had higher body mass index (BMI) sd scores, insulin, insulin resistance, uric acid, and adipocytokines and had more atherogenic lipoprotein profiles than other children. However, after being corrected by BMI sd, only high-density lipoprotein cholesterol, apolipoprotein A-I, IL-6, and TNF-alpha for boys and high-density lipoprotein cholesterol, apolipoprotein B, uric acid, IL-6, and TNF-alpha for girls were significantly correlated with CRP. IL-6 was the strongest predictive variable for CRP and accounted for 26.2 and 27.7% of the variability in serum concentrations of CRP in boys and girls, respectively. Serum concentrations of IL-6 were partly dependent on BMI sd and TNF-alpha in both boys and girls. CONCLUSION: Although serum concentrations of CRP are partly regulated by adipocytokines and conventional risk factors for ACHD, high CRP levels were associated with atherogenic profiles of cardiovascular risk factors in children. Our findings suggest that it may be important to control body weight to prevent an increase in serum CRP in children.

Low-density lipoprotein particle size and its regulatory factors in school children.

Small low-density lipoprotein (LDL) particles are more atherogenic than larger LDL particles. To help prevent atherosclerotic coronary heart diseases, it may be useful to understand risk factors during childhood. In the present study, we evaluated LDL size and its relationship to other risk factors for atherosclerotic coronary heart disease. LDL size was measured by 2-15% gradient gel electrophoresis in 586 Japanese children (316 boys and 270 girls). Plasma lipids, apolipoproteins (apo), glucose, and insulin were also determined by conventional methods. Pattern B (LDL size < 25.5 nm) was found in 10.8% of boys and 4.4% of girls. Children with pattern B had a higher body mass index (BMI) and insulin resistance and a more atherogenic lipoprotein profile [higher triglycerides, higher apoB, and lower high-density lipoprotein cholesterol (HDL-C)] than children with pattern A (LDL size > or = 25.5 nm). BMI, insulin resistance, and plasma concentrations of triglycerides, glucose, and insulin decreased and plasma concentrations of HDL-C and apoA-I increased as LDL size increased. HDL-C and insulin in boys, and BMI, HDL-C, and apoA-I in girls predicted 22.9 and 28.1% of the variability of LDL size, respectively. LDL size was correlated with BMI and plasma concentrations of HDL-C, apoA-I, and insulin. Although the contribution of these parameters to LDL size in children was less than that in adults, improvement of these parameters by changes in lifestyle might be important for preventing the development of atherosclerosis even in children.