Effect of aging and obesity on the expression of dyslipidaemia in children from families with familial combined hyperlipidaemia

Abstract

The aim of the present study was to delineate the mechanism(s) responsible for the increased secretion of VLDL (very-low-density lipoprotein) particles in patients with FCH (familial combined hyperlipidaemia). In 194 young adults (<25 years of age) recruited from families with FCH, we investigated how plasma lipids, (apo)lipoproteins and BMI (body mass index) varied with age. Furthermore, we performed a 5-year follow-up study of clinical and biochemical characteristics of a subset of this population (n=85) stratified by apoB (apolipoprotein B) levels (below or above the 75th percentile adjusted for age and gender). Plasma apoB concentration (r=0.45, P<0.0001), triacylglycerol (triglyceride) concentration (r=0.45, P<0.0001), LDL (low-density lipoprotein) subfraction profile (r=-0.46, P<0.0001) and BMI (r=0.51, P<0.0001) were significantly associated with age. Plasma apoB concentration in the hyperapoB group was already elevated at a young age, whereas other characteristics of FCH, as observed in adults, including triacylglycerol levels >1.5 mmol/l and/or small-dense LDL, were observed only sporadically. After the 5-year follow-up, BMI increased in both groups, and this increase was associated with changes in apoB (r=0.27, P<0.05), triacylglycerol (r=0.30, P<0.01), VLDL cholesterol (r=0.22, P<0.05), VLDL triacylglycerol (r=0.25, P<0.05) and high-density lipoprotein cholesterol (r=-0.27, P<0.05). In conclusion, we have found indirect evidence of a primary, presumably genetically determined, increase in plasma apoB concentration occurring early in life of offspring from families with FCH. However, aging-related post-maturation increases in adipose tissue mass also appear to contribute to an aggravation and/or modulation of this genetically determined apoB overproduction.

Triglycerides and Cardiovascular Disease

“…Although the phenotypic expression of FCHL is delayed until young adulthood, as childhood obesity rates increase, the higher adipose tissue mass that drives apo B secretion accelerates the number of cases of FCHL diagnosed in the young adult population. 145 Familial type III hyperlipoproteinemia or dysbetalipoproteinemia is due to the accumulation of cholesterol-rich VLDL, 146,147 which results in a higher ratio of core CE to triglyceride (Ͼ0.3) than in normal VLDL (0.2). The type III phenotype is often characterized by near-equivalent cholesterol and triglyceride values due to impaired receptor-mediated clearance, whereas the hypertriglyceridemia of type III reflects the impaired processing of remnants and increased VLDL hepatic production associated with increased levels of apo E. In this disorder, apo B is not a useful marker of overall atherogenicity, as in FCHL; non-HDL-C would be a more appropriate target.…”

Detection and Treatment of Children and Adolescents with Dyslipidemia

“…If the apoB or LDL-P are elevated in such children (Table 5.2), then the child probably has FCHL. The complete dyslipidemic expression of FCHL is often delayed until adulthood, although elevated apoB or LDL-P may be the first expression of FCHL in adolescents and young adults [112]. apoA-I can be measured in a child with a low HDL-C to determine the severity of the phenotype.…”

Clinical and laboratory assessment of cardiovascular risk in children: Guidelines for screening, evaluation, and treatment

“…However, elevated ApoB is the first expression of FCHL in adolescents and young adults. 70 Age-related factors, such as increased BMI, contribute to the degree of dyslipidemia in such youth.…”