Effect of aging and obesity on the expression of dyslipidaemia in children from families with familial combined hyperlipidaemia.
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.
ter Avest
Ewoud
E
Department of Medicine, Division of General Internal Medicine, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands. e.teravest@aig.umcn.nl
Sniderman
Allan D
AD
Bredie
Sebastian J H
SJ
Wiegman
Albert
A
Stalenhoef
Anton F H
AF
de Graaf
Jacqueline
J
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
D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D002784:Cholesterol