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CLINICAL RESEARCH: PROTEAN EFFECTS OF STATINS

Statins enhance postischemic hyperemia in the skin circulation of hypercholesterolemic patients

A monitoring test of endothelial dysfunction for clinical practice?

Christian Binggeli, MD^*, Lukas E. Spieker, MD^*, Roberto Corti, MD^*, Isabella Sudano, MD, PhD^*, Vesna Stojanovic, MD^*, Daniel Hayoz, MD, Thomas F. Lüscher, MD, FACC, FESC, FRCP^* and Georg Noll, MD, FESC^*,*

^* CardioVascular Center, Division of Cardiology, University Hospital, Zürich, Switzerland
Division of Hypertension and Vascular Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

Manuscript received September 11, 2002; revised manuscript received December 21, 2002, accepted January 9, 2003.

^* Reprint requests and correspondence: Dr. Georg Noll, Division of Cardiology, University Hospital, CH-8091 Zürich, Switzerland.
karnog{at}usz.unizh.ch

OBJECTIVES: The present study aims to investigate whether laser Doppler flowmetry can be used to monitor improvements in vascular function during statin therapy.

BACKGROUND: Endothelial dysfunction is an early feature of atherosclerosis in hypercholesterolemic patients and can be improved by statins. There are several methods to assess endothelial function in vivo, none of them being feasible in everyday practice.

METHODS: Skin perfusion, measured by laser Doppler flowmetry, was assessed at rest and during reactive hyperemia. Nineteen hypercholesterolemic patients (age 42 to 73 years, total cholesterol 5.4 to 9.6 mmol/l) were studied before and during statin therapy. To further investigate the mechanisms, postischemic skin hyperemia was measured before and after intradermal injection of the nitric oxide synthase inhibitor L-NAME and its inactive isoform D-NAME (0.5 µmol/10 µl each). On a separate day, the healthy volunteers were reexamined before and 2 h after 1,000 mg aspirin.

RESULTS: Postischemic skin blood flow was markedly reduced in hypercholesterolemic patients (45 ± 11%) compared with healthy controls (238 ± 20%, p < 0.0001) and improved after statin therapy (113 ± 15%, p = 0.0005 vs. pre-treatment). In the healthy volunteers, the hyperemic responses were not significantly different after L-NAME and D-NAME. Aspirin reduced hyperemia from 274 ± 49% to 197 ± 40% (p = 0.025).

CONCLUSIONS: Reactive hyperemia of the skin microcirculation can be easily and reproducibly assessed by laser Doppler flowmetry. Vasodilator prostaglandins are the major mediators of postischemic skin hyperemia, which is impaired in hypercholesterolemic patients and can be enhanced by cholesterol-lowering therapy. Thus, laser Doppler flowmetry may represent a tool to assess and monitor vascular function during therapy in everyday practice.

Abbreviations and Acronyms   D-NAME   N-omega-nitro-D-arginine methyl ester   HDL   high-density lipoprotein   LDL   low-density lipoprotein   L-NAME   N-omega-nitro-L-arginine methyl ester   NO   nitric oxide   PGI2   prostacyclin

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