ABSTRACT
Recent years have brought a significant amount of new results in the field of atherosclerosis. A better understanding of the role of different lipoprotein particles in the formation of atherosclerotic plaques is now possible. Recent cardiovascular clinical trials have also shed more light upon the efficacy and safety of novel compounds targeting the main pathways of atherosclerosis and its cardiovascular complications.In this review, we first provide a background consisting of the current understanding of the pathophysiology and treatment of atherosclerotic disease, followed by our future perspectives on several novel classes of drugs that target atherosclerosis. The focus of this update is on the pathophysiology and medical interventions of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and lipoprotein(a) (Lp(a)).
ABSTRACT
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.
