Published Online
on September 22, 2003

A more recent version of this article appeared on October 7, 2003

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Submitted on June 3, 2003
Revised on August 8, 2003
Accepted on August 9, 2003

Enhanced Interleukin-1 in Hypercholesterolemia. Effects of Simvastatin and Low-Dose Aspirin

Patrizia Ferroni MD, Francesca Martini PhD, Cristiano M. Cardarello MD, Pier Paolo Gazzaniga MD, Giovanni Davì MD^*, and Stefania Basili MD

From the Departments of Experimental Medicine & Pathology (P.F., F.M., P.P.G.) and Medical Therapy (C.M.C., S.B.), University of Rome, La Sapienza, and Center of Excellence on Aging (G.D.), University of Chieti "G. D'Annunzio" School of Medicine, Chieti, Italy.

^* To whom correspondence should be addressed. E-mail: gdavi{at}unich.it.

Background--This study was aimed at verifying whether activation of platelets might represent a source of interleukin (IL)-1 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-1 (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-1 (P<0.0001) levels were independently related to CRP by multiple regression analysis. Both drugs were associated with comparable, significant reductions in IL-1 and sP-selectin. Simvastatin, but not aspirin treatment, significantly lowered CRP levels (P<0.05). The change in IL-1 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-1 did not correlate with the change in CRP levels.

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

Key words: hypercholesterolemia • platelets • inflammation • aspirin • statins

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