Phenotype-dependent and -independent actions of rosuvastatin on atherogenic lipoprotein subfractions in hyperlipidaemia.
This randomised, double-blind, placebo-controlled crossover study evaluated the effects of rosuvastatin (40 mg/day for 8 weeks) on atherogenic apolipoprotein B-containing lipoprotein subfractions. Subjects, recruited based on raised plasma triglyceride (TG) or low-density lipoprotein cholesterol (LDL-C), were divided into normotriglyceridaemic (NTG, n = 13; TG < 2.0 mmol/l) and hypertriglyceridaemic (HTG, n = 16; TG > or = 2.0 mmol/l) groups. Similar reductions on rosuvastatin were observed for both groups in LDL-C (NTG -60%; HTG -56%), apoB (both -49%), intermediate-density lipoprotein (NTG -57%; HTG -54%) and LDL circulating mass (NTG -52%, HTG -58%) (all P < 0.001 versus placebo), i.e., these changes were phenotype independent. Phenotype dependency in response was observed in HTG relative to NTG in concentration of small dense LDL (LDL-III) (NTG -44%, P = NS; HTG -69%, P < 0.001), very-low-density lipoprotein1 (NTG -18%, P = NS; HTG 46%, P < 0.01), and remnant-like particle cholesterol (NTG -31%, P = NS; HTG -48%, P < 0.05). Rosuvastatin reduced cholesteryl ester transfer protein (CETP) by 33% in NTG and 37% in HTG (both P < 0.001); a reduction in cholesteryl ester transfer activity (-59%, P < 0.001) was observed in HTG only. Rosuvastatin therefore, in addition to lowering LDL and apoB-concentrations, largely corrected the TG and LDL abnormalities in subjects who had the propensity to develop the atherogenic lipoprotein phenotype.
Caslake
Muriel J
MJ
Department of Pathological Biochemistry, Glasgow Royal Infirmary University NHS Trust, 4th Floor Queen Elizabeth Building, 10 Alexandra Parade, Glasgow G31 2ER, UK. m.caslake@clinmed.gla.ac.uk
Stewart
Grace
G
Day
Stephen P
SP
Daly
Elaine
E
McTaggart
Fergus
F
Chapman
M John
MJ
Durrington
Paul
P
Laggner
Peter
P
Mackness
Michael
M
Pears
John
J
Packard
Chris J
CJ
D000284:Administration, Oral; D000328:Adult; D001053:Apolipoproteins / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000187:drug effects / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000187:drug effects* / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D011336:Probability; D011743:Pyrimidines / Q000008:administration & dosage*; D012016:Reference Values; D000068718:Rosuvastatin Calcium; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism*
D001053:Apolipoproteins; D005464:Fluorobenzenes; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011743:Pyrimidines; D013449:Sulfonamides; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D000068718:Rosuvastatin Calcium; D002784:Cholesterol