Low-dose of statin treatment improves cerebrovascular reactivity in patients with ischemic stroke: single photon emission computed tomography analysis.
BACKGROUND
Statins, 3-hydroxy-3-methylglutaryl-coenzymeA reductase inhibitors, have pleiotropic effects that are independent of their cholesterol-lowering activities. For example, they improve vascular endothelial function and exert anti-inflammatory effects. In large clinical trials they reduced the incidence of stroke and myocardial infarction; however, little is currently known regarding the mechanism or mechanisms underlying their clinically confirmed stroke protection.


METHODS
We assessed 10 patients who had experienced a stroke at least 6 months earlier; they received low-dose (5 mg) simvastatin. Using our triple-injection technetium 99m-ethylcysteinate dimer method, we determined their cerebral blood flow and cerebrovascular reactivity. A second assessment of at-rest cerebral blood flow and cerebrovascular reactivity was performed 4 or more months (mean 6 months) after the start of statin administration. We used acetazolamide (1 g) as the vasodilator. The region of interest was the middle cerebral artery territory on a 3-dimensional stereotaxic region of interest template.


RESULTS
Statin administration did not significantly affect the regional cerebral blood flow at rest. Before statin treatment, the patients' vasoreactivity, determined by the triple-injection technetium 99m-ethylcysteinate dimer method, demonstrated delayed, poor, or near-normal response patterns. Statin treatment improved vasoreactivity in all patients. Their mean serum total cholesterol level before statin administration was 200 mg/dL (range 187-256 mg/dL). Statin treatment significantly reduced their mean serum total cholesterol to 180 mg/dL (range 128-220 mg/dL) (P < .01).


CONCLUSIONS
The clinically confirmed stroke protection activity exerted by statins may be attributable to improved cerebrovascular reactivity.
Murakami
Masaji
M
Department of Neurosurgery, Kumamoto Takumadai Hospital, Kumamoto, Japan. mmurakami@horio-kai.or.jp
Fujioka
Shodo
S
Hirata
Yoshifumi
Y
Kuratsu
Jun-Ichi
J
D000368:Aged; D000369:Aged, 80 and over; D002536:Cerebral Arteries / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D003545:Cysteine / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D015609:Organotechnetium Compounds; D012008:Recurrence; D020521:Stroke / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000517:prevention & control*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015609:Organotechnetium Compounds; D002784:Cholesterol; C059659:technetium Tc 99m bicisate; D003545:Cysteine