Effect of rosuvastatin versus atorvastatin treatment on paraoxonase-1 activity in men with established cardiovascular disease and a low HDL-cholesterol.
OBJECTIVE
Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL) associated enzyme involved in the protective mechanisms of HDL. Our aim was to compare the effect of treatment with rosuvastatin and atorvastatin on serum PON-1 activity.


METHODS
We performed a prespecified prospective study in 68 patients, part of a larger, multicentre randomized study--RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport). Patients aged 40-80 years, all men, with established cardiovascular disease and high-density lipoprotein cholesterol (HDL-C) < 1.0 mmol/L (< 40 mg/dL) entered a 6-week dietary run-in period before receiving treatment with rosuvastatin 10 mg or atorvastatin 20 mg daily for 6-weeks. Doses were increased after 6 weeks to rosuvastatin 20 mg or atorvastatin 40 mg and after 12 weeks to rosuvastatin 40 mg or atorvastatin 80 mg daily. Serum PON-1 activity and lipid profile were determined at baseline, 6 and 18 weeks.


RESULTS
After 18 weeks, the rosuvastatin arm showed a significant increase of PON-1 activity (6.39 U/L, p = 0.02) whereas this was not observed in the atorvastatin arm (1.84 U/L, p = 0.77). The difference between groups did not reach significance (p = 0.11). Both rosuvastatin and atorvastatin resulted in significant (p = 0.0001) and similar increases in HDL-C after 6 weeks [0.06 mmol/L (2.32 mg/dL) vs. 0.05 mmol/L (1.93 mg/dL)] and after 18 weeks [0.10 mmol/L (3.87 mg/dL) vs. 0.10 mmol/L (3.87 mg/dL)].


CONCLUSIONS
Rosuvastatin treatment resulted in a significant increment of serum PON-1 activity with increasing dose while this was not observed with atorvastatin.
Bergheanu
S C
SC
Leiden University Medical Center, Leiden, The Netherlands.
Van Tol
A
A
Dallinga-Thie
G M
GM
Liem
A
A
Dunselman
P H J
PH
Van der Bom
J G
JG
Jukema
J W
JW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043303:Aryldialkylphosphatase / Q000097:blood*; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy*; D008076:Cholesterol, HDL / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
D008076:Cholesterol, HDL; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D043303:Aryldialkylphosphatase