Statins and Cerebral Vasomotor Reactivity

Abstract

See related article, pages 2540-2545. Animal models have shown that cholesterol-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (commonly called statins) may augment absolute cerebral blood flow (CBF) by enhancing nitric oxide synthase (eNOS).1 Statins upregulate type III endothelial eNOS in thrombocytes, decrease platelet activation, and protect from cerebral ischemia in normocholesterolemic mice.2 Statins may also provide additional beneficial effects by upregulating endogenous tissue plasminogen activator and enhancing clot lysis in a mouse model of embolic focal ischemia.3 Statins given 24 hours after experimental ischemia can enhance CBF, angiogenesis, neurogenesis and sinaptogenesis.4 How can these findings be applied in the clinical setting? A meta-analysis of published clinical trials showed that low-density lipoprotein–lowering with statins may decrease the risk of stroke in diabetic or hypertensive patients with normal low-density lipoprotein cholesterol at baseline, and in patients with coronary artery disease, with respectively 48%, 27% and 25% reduction in stroke incidence.5 Does any relationship exist among statins and cerebral vasomotor reactivity? Functional transcranial Doppler (TCD) ultrasonography permits the assessment of cognitively induced CBF velocity changes6 and the evaluation of cerebral vasomotor reactivity.7 TCD can be used to reliably evaluate age-related changes in the physiological response of the human cerebral circulation. A diminished nitric oxide–mediated cerebral vasomotor response may exist in aging subjects and in patients with vascular risk factors.8 Because there are no reliable markers for the functional status of the cerebral small vessels in elderly patients at risk of stroke, TCD studies may be useful. Although some parameters …