Impact of statin therapy on central aortic pressures and hemodynamics: principal results of the Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) Study.
BACKGROUND
Statins reduce the risk of cardiovascular events in people with hypertension. This benefit could arise from a beneficial effect of statins on central aortic pressures and hemodynamics. The Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) study, an Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy, investigated this hypothesis in a prospective placebo-controlled study of treated patients with hypertension.


RESULTS
CAFE-LLA recruited 891 patients randomized to atorvastatin 10 mg/d or placebo from 5 centers in the United Kingdom and Ireland. Radial artery applanation tonometry and pulse-wave analysis were used to derive central aortic pressures and hemodynamic indices at repeated visits over 3.5 years of follow-up. Atorvastatin lowered low-density lipoprotein cholesterol by 32.4 mg/dL (95% confidence interval [CI], 28.6 to 36.3) and total cholesterol by 35.1 mg/dL (95% confidence interval, 30.9 to 39.4) relative to placebo. Time-averaged brachial blood pressure was similar in CAFE-LLA patients randomized to atorvastatin or placebo (change in brachial systolic blood pressure, -0.1 mm Hg [95% CI, -1.8 to 1.6], P=0.9; change in brachial pulse pressure, -0.02 mm Hg [95% CI, -1.6 to 1.6], P=0.9). Atorvastatin did not influence central aortic pressures (change in aortic systolic blood pressure, -0.5 mm Hg [95% CI, -2.3 to 1.2], P=0.5; change in aortic pulse pressure, -0.4 mm Hg [95% CI, -1.9 to 1.0], P=0.6) and had no influence on augmentation index (change in augmentation index, -0.4%; 95% CI, -1.7 to 0.8; P=0.5) or heart rate (change in heart rate, 0.25 bpm; 95% CI, -1.3 to 1.8; P=0.7) compared with placebo. The effect of statin or placebo therapy was not modified by the blood pressure-lowering treatment strategy in the factorial design.


CONCLUSIONS
Statin therapy sufficient to significantly reduce cardiovascular events in treated hypertensive patients in ASCOT did not influence central aortic blood pressure or hemodynamics in a large representative cohort of ASCOT patients in CAFE-LLA.
Williams
Bryan
B
Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Building, Leicester Royal Infirmary, Leicester, UK. bw17@le.ac.uk
Lacy
Peter S
PS
Cruickshank
J Kennedy
JK
Collier
David
D
Hughes
Alun D
AD
Stanton
Alice
A
Thom
Simon
S
Thurston
Herbert
H
D001011:Aorta / Q000502:physiology*; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects*; D001916:Brachial Artery / Q000502:physiology; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011673:Pulsatile Flow / Q000187:drug effects; D011758:Pyrroles / Q000008:administration & dosage*; D017534:Radial Artery / Q000502:physiology; D016896:Treatment Outcome
D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D011758:Pyrroles; D000069059:Atorvastatin