Background and Purpose-Recent investigations have suggested an important role of statins in the prevention of stroke and dementia independent of their lipid-lowering properties. Using transcranial Doppler sonography (TCD), we examined acetazolamide reactivity as a marker of cerebral vasoreactivity in patients with subcortical small-vessel disease before and after pravastatin treatment. Methods-In 16 patients (mean age 68Ϯ10 years) with subcortical small-vessel disease, cerebral vasomotor reactivity was tested using TCD insonating the middle cerebral artery. Cerebral blood flow velocity (CBFV) increase after bolus injection of 1 g acetazolamide was determined before and after 2-month treatment with pravastatin sodium 20 mg daily. Results-Relative CBFV increase was significantly greater after pravastatin treatment (41.9Ϯ23.7% versus 55.7Ϯ18. 3%, Pϭ0.004). Comparison of CBFV at rest before and after treatment with pravastatin did not show significant differences.There was a strong negative correlation between the pravastatin-induced enhancement of vasomotor reactivity and the pretreatment CBFV increase (ϭϪ0. 64, Pϭ0.019). No associations were found between the effect of pravastatin on vasomotor reactivity and pretreatment levels or changes of LDL cholesterol. ecent studies have demonstrated a significant reduction of risk for ischemic stroke in patients with coronary heart disease treated with -hydroxy--methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins). 1 In addition, these agents may also prevent vascular dementia. 2 Current evidence suggests that the beneficial effects of statins on the vascular system seem to be mediated not only by their lipid-lowering properties but also by improving vascular endothelial function. They are known to activate endothelial nitric oxide synthase (eNOS) 3 and thereby propagate NOdependent vasodilation. In patients with cerebral small-vessel disease, impaired vasoregulation of the subcortical microvasculature may be an important pathogenetic mechanism, leading to white matter hypoperfusion, recurrent lacunar infarctions, and vascular dementia. Accordingly, reduced vasomotor reactivity as measured by transcranial Doppler (TCD) has been shown to correlate with the severity of leukoencephalopathy seen on MRI. 4,5 The purpose of the present pilot study was to investigate the effects of statin treatment on vasomotor reactivity in patients with cerebral small-vessel disease.
Conclusions-This
Subjects and MethodsWe prospectively studied 16 patients (9 men, 7 women; mean age 68Ϯ10 years) with subcortical small-vessel disease, defined by periventricular or subcortical white matter lesions on fluid-attenuated inversion recovery (FLAIR)-weighted MRI in addition to one or more of the following criteria: Ն1 ischemic events consistent with transient ischemic attack or lacunar infarction, history of cognitive decline, gait instability, and symptomatic epileptic seizure with no evident cause other than cerebral small-vessel disease. Exclusion criteria were previous statin treatm...