RESUMO
OBJECTIVE: To evaluate the relationship between remnant cholesterol and carotid intima-media thickness (cIMT), a surrogate marker for atherosclerosis, in children and adolescents. STUDY DESIGN: Anthropometric, laboratory, liver, and carotid ultrasonographic data were obtained from 767 youths (594, overweight/obese; 173, normal weight). Fasting remnant cholesterol was calculated from the standard lipid profile. cIMT ≥0.56 mm (corresponding to the 90th percentile of values observed in normal-weight children) was chosen to define elevated cIMT. Logistic regression analysis was used to estimate the risk of elevated cIMT according to tertiles of remnant cholesterol levels. RESULTS: In the entire cohort, the mean concentration of remnant cholesterol was 17.9 ± 10.3 mg/dL and mean cIMT value was 0.51 ± 0.8 mm. Remnant cholesterol significantly correlated with age, sex, body mass index, waist circumference, blood pressure, lipids, liver enzymes, and insulin resistance. cIMT value increased progressively with rising remnant cholesterol tertiles (Pfor trend < .001). Compared with subjects in the lowest remnant cholesterol tertile, those in the middle and highest remnant cholesterol tertiles had a 2.3- and 2.4-fold increased risk of elevated cIMT, independently of age, sex, pubertal stage, body mass index, and apolipoprotein B (all Padj ≤ .003). When the effects of overweight/obesity on the association between remnant cholesterol and cIMT were determined, normal-weight as well as overweight/obese subjects in the highest remnant cholesterol tertile had a 3.8- and 2.3-fold increased risk to have elevated cIMT compared with the respective study groups in the lowest tertile, after adjustment for conventional risk factors (Padj = .038 and Padj = .003, respectively). CONCLUSIONS: In youths, elevated levels of remnant cholesterol might represent a marker of early atherosclerotic damage.
Assuntos
Aterosclerose/diagnóstico por imagem , Espessura Intima-Media Carotídea , Colesterol/sangue , Hipercolesterolemia/fisiopatologia , Adolescente , Aterosclerose/etiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipercolesterolemia/diagnóstico , Modelos Lineares , Modelos Logísticos , Masculino , Obesidade Infantil/complicações , Fatores de RiscoRESUMO
OBJECTIVE: To evaluate the effectiveness of criteria based on child-parent assessment in predicting familial hypercholesterolemia (FH)-causative mutations in unselected children with hypercholesterolemia. STUDY DESIGN: LDLR, APOB, and PCSK9 genes were sequenced in 78 children and adolescents (mean age 8.4 ± 3.7 years) with clinically diagnosed FH. The presence of polygenic hypercholesterolemia was further evaluated by genotyping 6 low-density lipoprotein cholesterol (LDL-C)-raising single-nucleotide polymorphisms. RESULTS: Thirty-nine children (50.0%) were found to carry LDLR mutant alleles but none with APOB or PCSK9 mutant alleles. Overall, 27 different LDLR mutations were identified, and 2 were novel. Children carrying mutations showed higher LDL-C (215.2 ± 52.7 mg/dL vs 181.0 ± 44.6 mg/dL, P <.001) and apolipoprotein B levels (131.6 ± 38.3 mg/dL vs 100.3 ± 30.0 mg/dL, P <.004), compared with noncarriers. A LDL-C of ~190 mg/dL was the optimal value to discriminate children with and without LDLR mutations. When different diagnostic criteria were compared, those proposed by the European Atherosclerosis Society showed a reasonable balance between sensitivity and specificity in the identification of LDLR mutations. In children without mutation, the FH phenotype was not caused by the aggregation of LDL-C raising single-nucleotide polymorphisms. CONCLUSIONS: In unselected children with hypercholesterolemia, LDL-C levels >190 mg/dL and a positive family history of hypercholesterolemia appeared to be the most reliable criteria for detecting FH. As 50% of children with suspected FH did not carry FH-causing mutations, genetic testing should be considered.