Effects of short term atorvastatin treatment on cerebral hemodynamics in CADASIL.
BACKGROUND
HMG-CoA-reductase-inhibitors (statins) exhibit pleiotropic beneficial effects on the vascular system including induction of endothelial nitric oxide synthase (eNOS) expression which is critical for vasodilation. Recent studies suggest a beneficial effect of statins on cerebral vasoreactivity in patients with cerebral small vessel disease (SVD). CADASIL is a monogenic form of SVD caused by mutations in the Notch3 gene. Treatment options are limited and little is known about the therapeutic role of statins in CADASIL.


METHODS
Twenty-four CADASIL subjects were treated with atorvastatin for 8 weeks. Treatment was started with 40 mg, followed by a dosage increase to 80 mg after 4 weeks. Transcranial Doppler sonography measuring mean flow velocity (MFV) in the middle cerebral artery was performed at baseline and the end of the treatment period. Vasoreactivity was assessed by hypercapnia and intravenous application of l-Arginine, which is the substrate for eNOS.


RESULTS
There was no significant treatment effect on MFV (p=0.5) or cerebral vasoreactivity as assessed by hypercapnia (p=0.5) and intravenous l-Arginine (p=0.4) in the overall cohort. However, an inverse correlation was found between vasoreactivity at baseline and changes of both CO2 and l-Arginine-induced vasomotor response (both p<0.05).


CONCLUSIONS
Short term treatment with atorvastatin resulted in no significant improvement of hemodynamic parameters in the overall cohort of CADASIL subjects.
Peters
Nils
N
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, D-81377 Munich, Germany. Nils.Peters@med.uni-muenchen.de
Freilinger
Tobias
T
Opherk
Christian
C
Pfefferkorn
Thomas
T
Dichgans
Martin
M
D000328:Adult; D001120:Arginine / Q000494:pharmacology; D000069059:Atorvastatin; D046589:CADASIL / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D002245:Carbon Dioxide / Q000097:blood; D002536:Cerebral Arteries / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006935:Hypercapnia / Q000139:chemically induced / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use*; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002245:Carbon Dioxide; D009569:Nitric Oxide; D001120:Arginine; D000069059:Atorvastatin