Effects of Atorvastatin on some inflammatory parameters in severe primary hypercholesterolemia.

Recent publications have reanimated the point of view that there exist links between atherosclerosis--inflammation and hypercholesterolemia. The aim of our study was to investigate the possible influence of statins on some inflammatory parameters in persons with severe primary hypercholesterolemia (PHC). The effects of the HMG CoA reductase inhibitor--Atorvastatin--on serum lipids, apoproteins, C reactive protein (CRP), soluble Intercellular Adhesion Molecule (sICAM), lipid peroxides, antibodies to oxidized LDL (Ab oxLDL) and homocystein were evaluated in 21 persons (52.9 +/- 8.38 years old) with severe PHC, 12 of these having significant coronary-artery stenosis (diameter stenosis > or = 70%), in at least one major coronary artery branch. Ab oxLDL, sICAM, TBARS, CRP and homocystein were significantly increased (p < 0.05) in patients with coronary-artery stenosis. Following a 4 weeks hypolipemiant free baseline period, all persons were treated with Atorvastatin 40 mg once daily for 8 weeks. Atorvastatin 40 mg resulted in a reduction of LDL-C with 57.8% (baseline 259.6 +/- 71.39 mg%) p < 0.001, total Cholesterol with 44.08% (baseline 343.1 +/- 71.72 mg%) p < 0.001, Apo B with 50.6% (baseline 194.7 +/- 48.71 mg%) p < 0.001, TG with 12.02% (baseline 177.4 +/- 83.63 mg%) and HDL-C was increased with 6.84% (baseline 48.0 +/- 7.86 mg%). In coronary heart disease patients, Atorvastatin reduced homocystein concentrations with 19.41% (baseline 17.7 +/- 11.16 microM/l) (p < 0.01), and CRP with 21.9% (baseline 4.8 +/- 4.19 mg/l) p < 0.01 and TBARS with 52% (baseline 0.87 +/- 0.89 nM/ml) p < 0.001, but did not influence sICAM and Ab oxLDL. Thus atherogenic concentrations of LDL-C have to be closely modulated by minimal changes in LDL oxidative state. The effects of Atorvastatin on inflammatory parameters may crucially contribute to the clinical benefit of statins, independent of cholesterol lowering. Plaque stabilization may be a paradigm for antiinflammatory mechanism of action by this class of drugs.