title: High-dose atorvastatin enhances impaired cerebral vasomotor reactivity.
abstract: The influence of statin therapy on cerebral vasomotor function has not been fully characterized. We report the effects of high-dose atorvastatin therapy on cerebral vasomotor reactivity (VMR) in patients with controlled hypertension and dyslipidemia. We prospectively enrolled 36 patients with controlled hypertension and a low-density lipoprotein (LDL) cholesterol concentration >100 mg/dL. Atorvastatin 80 mg was given daily for 6 months and then discontinued. VMR was assessed by hypercapnic and hypocapnic transcranial Doppler challenge in both the right and left middle cerebral artery (MCA) at baseline, and after 3 and 6 months of therapy. Forty-five days after statin cessation, a repeat VMR was performed. VMR impairment was defined as ≤70%. Blood pressure, lipid levels, liver function, and creatine kinase level were monitored. Mean patient age was 60 years, 16 were men, and 13 had a previous history of subcortical infarction. Mean LDL cholesterol level before treatment was 154 ± 30 mg/dL. Atorvastatin lowered LDL by 53% at 3 months and by 46% at 6 months. Baseline VMR was 71% ± 21% in the right MCA and 70% ± 19% in the left MCA. No significant effect of atorvastatin on VMR was seen at 3 months and 6 months in the study population as a whole. In the subgroup of patients with baseline VMR impairment, atorvastatin therapy was associated with significantly improved VMR at both 3 and 6 months. This effect persisted for at least 45 days after discontinuation of therapy. Our findings indicate that high-dose atorvastatin therapy can significantly improve impaired cerebral VMR, and that the effects of atorvastatin on VMR persist for 1.5 months after discontinuation of therapy. We found no benefit of atorvastatin therapy in patients with preserved baseline vasoreactivity.
authors.affiliation: Cardiac and Stroke Institute, Jackson Memorial Hospital, Miami, Florida, USA. aforteza@med.miami.edu
authors.forename: Alejandro
authors.initials: A
authors.lastname: Forteza
authors.forename: Jose G
authors.initials: JG
authors.lastname: Romano
authors.forename: Iszet
authors.initials: I
authors.lastname: Campo-Bustillo
authors.forename: Nelly
authors.initials: N
authors.lastname: Campo
authors.forename: Diogo C
authors.initials: DC
authors.lastname: Haussen
authors.forename: Jose
authors.initials: J
authors.lastname: Gutierrez
authors.forename: Sebastian
authors.initials: S
authors.lastname: Koch
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D020520:Brain Infarction / Q000208:ethnology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016009:Chi-Square Distribution; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005431:Florida; D006439:Hemodynamics / Q000187:drug effects*; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006630:Hispanic or Latino; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000208:ethnology / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy / Q000208:ethnology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000187:drug effects*; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin