Background— This study was aimed at verifying whether activation of platelets might represent a source of interleukin (IL)-1β 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-1β ( P P P P P P P Conclusions— This study suggests that platelets might contribute to IL-1β production in hypercholesterolemia, thus providing an additional link between inflammation and the prothrombotic state in this setting.