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(Stroke. 2006;37:2054.)
© 2006 American Heart Association, Inc.

Original Contributions

Statin Treatment Is Not Associated With Consistent Alterations in Inflammatory Status of Carotid Atherosclerotic Plaques

A Retrospective Study in 378 Patients Undergoing Carotid Endarterectomy

Bart A.N. Verhoeven, MD, PhD; Frans L. Moll, MD, PhD; Johan A.F. Koekkoek; Allard C. van der Wal, MD, PhD; Dominique P.V. de Kleijn, PhD; Jean Paul P.M. de Vries, MD, PhD; Jan H. Verheijen, PhD; Evelyn Velema, Bsc; Els Busser, Bsc; Arjan Schoneveld, Bsc; Renu Virmani, MD, PhD Gerard Pasterkamp, MD, PhD

From the Departments of Vascular Surgery (B.A.N.V., F.L.M.) and Experimental Cardiology Laboratory (J.A.F.K., D.P.V.d.K., E.V., E.B., G.P.), University Medical Centre Utrecht, Utrecht, The Netherlands; the Cardiovascular Pathology (A.C.v.d.W.), Academic Medical Centre, University of Amsterdam, The Netherlands; the Interuniversity Cardiology Institute of The Netherlands, Utrecht, The Netherlands (D.P.V.d.K., A.S.); the Department of Vascular Surgery (J.P.P.M.d.V.), St. Antonius Hospital Nieuwegein, The Netherlands; the Biomedical Research (J.H.V.); de Nederlandse Organisatie voor toegepast-natuurwetenschappelijk onderzoek Quality of Life, Leiden, The Netherlands; and the Department of Cardiovascular Pathology (R.V.), Armed Forces Institute of Pathology, Washington, DC, USA.

Correspondence to G. Pasterkamp, MD, PhD, Experimental Cardiology Laboratory, Heidelberglaan 100, Room G02-523, 3584 CX Utrecht, The Netherlands. E-mail g.pasterkamp{at}umcutrecht.nl

Background and Purpose— Anti-inflammatory qualities are held partially responsible for the reduction of cardiovascular events after statin treatment. We examined the phenotype of carotid atherosclerotic plaques harvested during carotid endarterectomy in relation to the previous use of different statins prescribed in clinical practice.

Methods— Three hundred and seventy-eight patients were included. Atherosclerotic plaques were harvested, immunohistochemically stained and semiquantitively examined for the presence of macrophages (CD68), smooth muscle cells, collagen and fat. Adjacent atherosclerotic plaques were used to study protease activity and interleukin levels. Patients’ demographics were recorded and blood samples were stored.

Results— Serum cholesterol, low-density lipoprotein, apolipoprotein B, and C-reactive protein levels were lower in patients treated with statins compared with patients without statin treatment. Atheromatous plaques were less prevalent in patients receiving statins compared with patients without statin therapy (29% versus 42%, P=0.04). An increase of CD68 positive cells was observed in patients receiving statins compared with nonstatin treatment (P=0.05). This effect was specifically related to atorvastatin treatment. In patients treated with atorvastatin, the increased amount of CD68 positive cells were not associated with increased protease activity. In contrast, a dose-dependent decrease in protease activity was shown in the atorvastatin group. Interleukin 6 expression was lower in plaques obtained from patients treated with statins (P=0.04).

Conclusions— Statin use may exert pleiotropic effects on plaque phenotype. However, not the presence of macrophages but activation with subsequent protease and cytokine release may be attenuated by statin use.

Key Words: carotid endarterectomy • inflammation • pharmacology