title: 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.
authors.affiliation: Department of Medicine, Division of General Internal Medicine, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands. e.teravest@aig.umcn.nl
authors.forename: Ewoud
authors.initials: E
authors.lastname: ter Avest
authors.forename: Allan D
authors.initials: AD
authors.lastname: Sniderman
authors.forename: Sebastian J H
authors.initials: SJ
authors.lastname: Bredie
authors.forename: Albert
authors.initials: A
authors.lastname: Wiegman
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Graaf
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D001055:Apolipoproteins B / Q000097:blood; D015992:Body Mass Index; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D050171:Dyslipidemias / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000378:metabolism*; D007333:Insulin Resistance; D008019:Life Style; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D009765:Obesity / Q000378:metabolism*; D010641:Phenotype; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood
chemical_list: D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D002784:Cholesterol