Direct in vivo evidence of a vascular statin: a single dose of cerivastatin rapidly increases vascular endothelial responsiveness in healthy normocholesterolaemic subjects.
OBJECTIVE
HMG-CoA reductase inhibitors (statins) have been demonstrated to have in vitro vascular effects. The aim of this study was to determine whether statins actually have in vivo vascular effects independent of their cholesterol-lowering effect.


METHODS
We investigated the effect of a single dose of cerivastatin on vascular endothelial function by measuring flow-mediated dilatation of the brachial artery on ultrasound in 30 healthy volunteers with normal serum cholesterol concentrations. They were randomized to either placebo group (n = 15) or cerivastatin group (n = 15), and flow-mediated dilatation and endothelium-dependent dilatation were evaluated at before and 1 h, 3 h, 6 h, and 12 h after administration of placebo or cerivastatin.


RESULTS
There were no differences in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde-LDL, and high-sensitivity C-reactive protein before and after administration of placebo or cerivastatin. Cerivastatin significantly increased flow-mediated dilatation at 3 h (P < 0.001), and this increase rapidly returned to the baseline level 6 h after administration. Endothelium--independent dilatation of brachial artery was not altered.


CONCLUSIONS
A single dose of cerivastatin increased vascular endothelial responsiveness. Our data suggest that cerivastatin has a direct effect on the blood vessels that is independent of its lipid-lowering effect, and thus can be considered as a vascular statin.
Omori
Hisako
H
Department of Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan.
Nagashima
Hirotaka
H
Tsurumi
Yukio
Y
Takagi
Atsushi
A
Ishizuka
Naoko
N
Hagiwara
Nobuhisa
N
Kawana
Masatoshi
M
Kasanuki
Hiroshi
H
D000328:Adult; D000704:Analysis of Variance; D001783:Blood Flow Velocity / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects*; D004311:Double-Blind Method; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; C086276:cerivastatin