Pleiotropic effects of atorvastatin in heart failure: role in oxidative stress, inflammation, endothelial function, and exercise capacity.
BACKGROUND
Increased oxidative stress, a common feature in chronic heart failure, has been associated with inflammation, endothelial dysfunction, and extracellular matrix degradation. Statins have known anti-inflammatory and anti-oxidant effects; however, their role in chronic heart failure is still controversial.


METHODS
This was a prospective study of 38 patients with stable systolic chronic heart failure. Patients received a 4-week placebo course, followed by atorvastatin 20 mg/day for 8 weeks. Oxidative stress, inflammation and remodeling markers, brachial artery flow-mediated vasodilation, and 6-minute walk test were evaluated at baseline, 4, and 8 weeks.


RESULTS
Mean age was 58 +/- 12. Mean left ventricular ejection fraction was 27% +/- 12%. No significant differences were observed between measurements at baseline and after placebo. Atorvastatin induced a significant decrease of matrix metalloproteinase-9 activity, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-6, and malondialdehyde, and a significant increase of endothelial superoxide dismutase activity when compared with placebo. No differences in tissue inhibitor of matrix metalloproteinase and matrix metalloproteinase-2 activities were observed. Atorvastatin use was associated with an improved flow-dependent brachial vasodilation and exercise capacity in the 6-minute walk test.


CONCLUSIONS
In chronic heart failure patients, atorvastatin therapy is associated with a decrease of inflammation and extracellular matrix remodeling, improving both endothelial function and exercise capacity.
Castro
Pablo F
PF
Departamento de Enfermedades Cardiovasculares, Hospital Clínico, Pontificia Universidad Católica de Chile, Santiago, Chile. pcastro@med.puc.cl
Miranda
Rodrigo
R
Verdejo
Hugo E
HE
Greig
Douglas
D
Gabrielli
Luigi A
LA
Alcaino
Hernán
H
Chiong
Mario
M
Bustos
Carlos
C
Garcia
Lorena
L
Mellado
Rosemarie
R
Vukasovic
José Luis
JL
Godoy
Ivan
I
Lavandero
Sergio
S
D000368:Aged; D000069059:Atorvastatin; D015415:Biomarkers / Q000378:metabolism; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D017079:Exercise Tolerance; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011446:Prospective Studies; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D014664:Vasodilation; D016138:Walking
D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin