Secondary prevention with fluvastatin decreases levels of adhesion molecules, neopterin and C-reactive protein

Treatment of hypercholesterolaemia with HMG-CoA reductase inhibitors results in an earlier reduction of morbidity and mortality than expected from trials using conventional cholesterol-lowering therapies. Possible explanations for this effect include stimulation of angiogenesis, improvement of endothelial function, plaque stabilisation, inhibition of coagulation and/or thrombocyte aggregation and inhibition of the inflammatory response associated with atherosclerosis.

We investigated whether statins exert their effects by inhibition of endothelial activation, inflammation and/or monocyte/macrophage activation by measuring plasma levels of soluble cell adhesion molecules, neopterin and C-reactive protein upon treatment with fluvastatin for a period of 12 months in patients with established atherosclerosis and hypercholesterolaemia.

Blood samples were taken at baseline and at 3 and 12 months after starting treatment with fluvastatin 80 mg daily. Upon treatment, a reduction of s-ICAM-1 (956.3+/-123.6 vs. 745.4+/-127.4 vs. 674.9+/-70.8 ng/ml, P<0.05) and s-E-selectin (58.6+/-6.7 vs. 47.0+/-6.1 vs. 44.9+/-3.2 ng/ml, P<0.01) was observed. In addition, levels of neopterin decreased, albeit transiently (7.1+/-0.7 vs. 6.0+/-0.5 vs. 6.5+/-0.8 nmol/l, P=0.02), suggesting a reduction in monocyte/macrophage activity. Moreover, we found a decrease in levels of C-reactive protein during follow-up (5.21+/-2.0 vs. 3.18+/-0.7 vs. 1.95+/-0.3 mg/l, P<0.05), compatible with a reduction in inflammatory activity.

We conclude that statins have a combined beneficial effect on monocyte/macrophage activity, endothelial function and systemic inflammatory activity.