Effect of increasing doses of rosuvastatin and atorvastatin on apolipoproteins,

enzymes involved in lipoprotein metabolism and inflammatory parameters

Detailed results of the prospective randomized RADAR
(Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport) study

Karalis I, Bergheanu SC, van Tol A, Dallinga-Thie GM , Liem AH, Jukema JW

Leiden University Medical Center

Background: Methods:
Statins have substantially decreased incidence of cardiovascular events but the exact - 75 male patients, aged 40-80 years, with known
pathophysiological mechanism of their beneficial effect is yet unclear. We aimed to examine the cardiovascular disease and low HDL-C (<1.0 mmol/l),
effects of up-titrated doses of 2 widely used statins (atorvastatin (ATOR) and rosuvastatin were randomized to receive, after an initial 6 week
(ROSU)) on parameters involved in lipoprotein metabolism, in patients with low high density dietary run-in phase, either ATOR 20 mg (n=38) or ROSU
lipoprotein cholesterol values (HDL-C). 10 mg (n=37)
- Doses were up-titrated (in 6 week intervals) to 80 mg
Results: of ATOR or 40 mg of ROSU at 12 weeks

- Both statins significantly reduced total cholesterol (TChol) and non-HDL-C values with ROSU - Serum lipoproteins and lipoprotein metabolism
being more effective for the doses studied (p<0.05). No statistically significant effect on HDL-C parameters were measured at baseline and at 6 and 18
was observed for either statin. weeks of follow up

- Apolipoproteins (apo) B, CI, CIII, AV and E were significantly reduced in both groups
(p<0.05), while the ratio of apoAI+AII over apoAI was changed for both statins with the Radar study design
decrease of apoAI being more prominent in the ATOR group (p=0.01).
- Cholesterol ester transfer protein (CETP) mass and activity, phospholipid transfer protein
(PLTP) activity and platelet activating factor acyl hydrolase (PAFAH) mass and activity were all
significantly reduced in both treatment groups over the follow up period (p<0.001). ATOR
displayed a more prominent decrease of PLTP activity compared to ROSU (p=0.03) while ROSU
displayed a more prominent decrease of PAFAH activity compared to ATOR (p=0.03).
- Both statins effectively reduced, in a dose-dependent way, high sensitivity C reactive protein
values over time, while no effect on the levels of circulating inter cellular adhesion molecule 1
(cICAM-1) was observed.

Conclusion
The beneficial effects of statin treatment extend further and beyond a mere TChol and LDL cholesterol reduction, as demonstrated by the aforementioned
alterations of lipoproteins, enzymes and lipid transfer proteins involved in lipoprotein metabolism and pro-atherogenic and inflammatory molecules. ROSU and
ATOR displayed discrete differences. The reported data provide an insight for the possible pathophysiological mechanisms implicated in the beneficial effect of
increasing dosages of different statin treatments.