Effects of rosuvastatin and atorvastatin on LDL and HDL particle concentrations in patients with metabolic syndrome: a randomized, double-blind, controlled study.
OBJECTIVE
The purpose of this study was to examine the effects of statin therapy on lipoprotein particle concentrations in patients with the metabolic syndrome. Changes in lipoprotein particle concentration may predict the risk of coronary heart disease more accurately than lipoprotein cholesterol levels.


METHODS
Patients with dyslipidemia and the metabolic syndrome (n = 318) were randomly assigned in a double-blind study comparing 10 mg rosuvastatin (RSV), 10 mg atorvastatin, or placebo daily for 6 weeks. From weeks 6 to 12, patients in the RSV and placebo groups received 20 mg RSV, whereas the ATV group increased their dose to 20 mg daily. Lipoprotein particle concentrations were measured by nuclear magnetic resonance spectroscopy, LDL cholesterol was measured by beta-quantification, and other lipoproteins were measured by standard methods at baseline, 6 weeks, and 12 weeks. Lipoprotein levels were compared by analysis of covariance.


RESULTS
Statins reduced LDL particle concentration less than LDL cholesterol (-30 to -38 vs. -38 to -51%). Reductions were greater with RSV than with ATV (P < 0.05 for LDL particle concentration and P < 0.001 for LDL cholesterol). Most patients attained LDL cholesterol <2.59 mmol/l (100 mg/dl) at 12 weeks (80% with RSV and 59% with ATV; P = 0.003), but only 27% of patients receiving RSV and 19% receiving ATV attained the goal of LDL particle concentration <1,000 nmol/l (P = 0.07).


CONCLUSIONS
In patients with the metabolic syndrome, statin-induced changes in LDL cholesterol do not accurately reflect changes in LDL particle concentration. Consequently, despite attainment of LDL cholesterol goals, these patients may retain considerable residual coronary heart disease risk.
Rosenson
Robert S
RS
University of Michigan, Ann Arbor, Michigan, USA. rrosenso@umich.edu
Otvos
James D
JD
Hsia
Judith
J
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D016632:Apolipoprotein A-I / Q000097:blood / Q000187:drug effects; D000069059:Atorvastatin; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood* / Q000187:drug effects; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000150:complications* / Q000188:drug therapy*; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged; D010919:Placebos; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D044465:White People
D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D010919:Placebos; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D014280:Triglycerides; D000068718:Rosuvastatin Calcium; D002784:Cholesterol; D000069059:Atorvastatin