title: Cholesterol synthesis is increased in mixed hyperlipidaemia.
abstract: We showed previously that hypertriglyceridaemia, but not hypercholesterolaemia, is correlated with increases in cholesterol synthesis and apolipoprotein B secretion in patients with secondary hypertriglyceridaemia. The aim of the present study was to compare the rate of cholesterol synthesis, using fasting plasma mevalonic acid (MVA) as an index, in patients with primary mixed hyperlipidaemia (type IIb phenotype, n=45) and primary hypercholesterolaemia (type IIa phenotype, n=92). LDL cholesterol was significantly higher in types IIa (6.38+/-0.18 mmol/l) and IIb (5.89+/-0.25 mmol/l) compared to 40 normolipidaemic controls (2. 99+/-0.1 mmol/l, P<0.0001), whereas serum triglyceride was higher in type IIb (2.62 (range 2.2-3.0) mmol/l) than type IIa (1.22 (range 0. 85-1.60) mmol/l, P<0.001) and controls (0.90 (range 0.68-1.24) mmol/l, P<0.001). Similarly, MVA was higher in type IIb (7.0+/-0.46 ng/ml) than IIa (5.6+/-0.23 ng/ml, P<0.0) and controls (5.6+/-0.36 ng/ml, P<0.05). Plasma MVA correlated positively with serum triglyceride (r=0.22, P=0.004) and negatively with LDL cholesterol (r=-0.21, P=0.014). These results are in accordance with previous observations that VLDL-apolipoprotein B secretion and cholesterol synthesis are linked and demonstrate that the latter is increased in mixed hyperlipidaemia.
authors.affiliation: MRC Lipoprotein Team, Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W2 ONN, UK. rnaoumov@rpms.ac.uk
authors.forename: R P
authors.initials: RP
authors.lastname: Naoumova
authors.forename: K D
authors.initials: KD
authors.lastname: Kim
authors.forename: C
authors.initials: C
authors.lastname: Neuwirth
authors.forename: S
authors.initials: S
authors.lastname: Niththyananthan
authors.forename: N B
authors.initials: NB
authors.lastname: Rendell
authors.forename: G W
authors.initials: GW
authors.lastname: Taylor
authors.forename: G R
authors.initials: GR
authors.lastname: Thompson
mesh_terms: D000328:Adult; D001057:Apolipoproteins E; D002784:Cholesterol / Q000096:biosynthesis*; D008078:Cholesterol, LDL / Q000097:blood; D005215:Fasting; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D006949:Hyperlipidemias / Q000097:blood*; D006938:Hyperlipoproteinemia Type II / Q000097:blood; D008297:Male; D008798:Mevalonic Acid / Q000097:blood; D010641:Phenotype; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid