Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers.
We measured plasma markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, and cholestanol) in order to compare the effects of maximal doses of rosuvastatin with atorvastatin and investigate the basis for the significant individual variation in lipid lowering response to statin therapy. Measurements were performed in participants (n = 135) at baseline and after 6 weeks on either rosuvastatin (40 mg/day) or atorvastatin (80 mg/day) therapy. Plasma sterols were measured using gas-liquid chromatography. Rosuvastatin and atorvastatin significantly (P < 0.001) altered plasma total cholesterol (C) levels by -40%, and the ratios of lathosterol/C by -64% and -68%, and campesterol/C by +52% and +72%, respectively, with significant differences (P < 0.001) between the treatment groups for the latter parameter. When using absolute values of these markers, subjects with the greatest reductions in both synthesis (lathosterol) and absorption (campesterol) had significantly greater reductions in total C than subjects in whom the converse was true (-46% versus -34%, P = 0.001), with similar effects for LDL-C. Rosuvastatin and atorvastatin decreased markers of cholesterol synthesis and increased markers of fractional cholesterol absorption, with rosuvastatin having significantly less effect on the latter parameter than atorvastatin. In addition, alterations in absolute values of plasma sterols correlated with the cholesterol lowering response.
van Himbergen
Thomas M
TM
Lipid Metabolism Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. thomas.vanhimbergen@tufts.edu
Matthan
Nirupa R
NR
Resteghini
Nancy A
NA
Otokozawa
Seiko
S
Ai
Masumi
M
Stein
Evan A
EA
Jones
Peter H
PH
Schaefer
Ernst J
EJ
D000042:Absorption / Q000187:drug effects; D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000097:blood*; D048909:Diabetes Complications / Q000097:blood; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage*; D017127:Glycation End Products, Advanced; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000097:blood; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D000068718:Rosuvastatin Calcium; D012709:Serum Albumin / Q000378:metabolism; D013261:Sterols / Q000097:blood; D013449:Sulfonamides / Q000008:administration & dosage*; D000093423:Glycated Serum Albumin
D015415:Biomarkers; D005464:Fluorobenzenes; D017127:Glycation End Products, Advanced; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008074:Lipoproteins; D010840:Phytosterols; D011743:Pyrimidines; D011758:Pyrroles; D012709:Serum Albumin; D013261:Sterols; D013449:Sulfonamides; C021273:campesterol; C001521:lathosterol; D000068718:Rosuvastatin Calcium; D002784:Cholesterol; D000069059:Atorvastatin; D000093423:Glycated Serum Albumin