title: Statins enhance postischemic hyperemia in the skin circulation of hypercholesterolemic patients: a monitoring test of endothelial dysfunction for clinical practice?
abstract: OBJECTIVE
  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 micromol/10 microl 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.
authors.affiliation: CardioVascular Center, Division of Cardiology, University Hospital, CH-8091 Zürich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Binggeli
authors.forename: Lukas E
authors.initials: LE
authors.lastname: Spieker
authors.forename: Roberto
authors.initials: R
authors.lastname: Corti
authors.forename: Isabella
authors.initials: I
authors.lastname: Sudano
authors.forename: Vesna
authors.initials: V
authors.lastname: Stojanovic
authors.forename: Daniel
authors.initials: D
authors.lastname: Hayoz
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Georg
authors.initials: G
authors.lastname: Noll
mesh_terms: D000328:Adult; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000503:physiopathology*; D006940:Hyperemia / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008991:Monitoring, Physiologic; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors