Enhanced Interleukin-1beta in Hypercholesterolemia: Effects of Simvastatin and Low-dose Aspirin

Background: This study was aimed at verifying whether activation of platelets might represent a source of interleukin (IL)-1beta levels in hypercholesterolemia. To this purpose, we compared the effects of a short-term treatment with simvastatin or low-dose aspirin on circulating levels of this cytokine.

Methods And Results: Fifty patients with hypercholesterolemia were randomly allocated to receive an 8-week therapeutic course of simvastatin 20 mg daily (n=25) or aspirin 100 mg daily (n=25). Baseline soluble (s) P-selectin directly correlated with IL-1beta (P<0.0001) and C-reactive protein (CRP) (P<0.05) but not with von Willebrand factor, total cholesterol, or LDL cholesterol levels. Furthermore, sP-selectin (P<0.02) and IL-1beta (P<0.0001) levels were independently related to CRP by multiple regression analysis. Both drugs were associated with comparable, significant reductions in IL-1beta and sP-selectin. Simvastatin, but not aspirin treatment, significantly lowered CRP levels (P<0.05). The change in IL-1beta levels correlated with the change in sP-selectin in patients randomized to either simvastatin (Rho, 0.42; P<0.05) or aspirin (Rho, 0.42; P<0.05). In contrast, the simvastatin-induced change in IL-1beta did not correlate with the change in CRP levels.

Conclusions: This study suggests that platelets might contribute to IL-1beta production in hypercholesterolemia, thus providing an additional link between inflammation and the prothrombotic state in this setting.