Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure.
BACKGROUND
Heart failure has been associated with impaired endothelial function, increased inflammatory process and elevated oxidative stress status. Both statins and vitamin E separately improve endothelial function in patients with hypercholesterolemia and/or advanced atherosclerosis.


OBJECTIVE
To evaluate the effect of atorvastatin alone or in combination with vitamin E on endothelial function and serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and vascular cells adhesion molecule (sVCAM-1) in patients with ischemic heart failure.


METHODS
Thirty-eight male patients with ischemic cardiomyopathy were randomly divided into three groups and received either atorvastatin 10 mg/day (n = 14), a combination of atorvastatin 10 mg/day plus vitamin E 400 IU/day (n = 12), or no statin or antioxidant treatment (n=12, controls) for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was defined as the percent change of FBF from rest to the maximum flow during reactive hyperemia or after nitrate administration, respectively.


RESULTS
RH% was significantly improved in both the atorvastatin-treated (p < 0.01) and atorvastatin plus vitamin E groups (p < 0.05), but the increase was significantly higher in the atorvastatin-treated group (p < 0.05). Serum levels of IL-6, TNF-alpha and sVCAM-1 were decreased in the atorvastatin-treated group (p < 0.05 for all), but remained unaffected in the other two groups (p = NS for all).


CONCLUSIONS
Low dose atorvastatin treatment improves endothelial function and reduces the expression of proinflammatory cytokines and adhesion molecules in patients with ischemic heart failure, an effect partly depressed by vitamin E.
Tousoulis
Dimitris
D
Cardiology Unit, Hippokration Hospital, Athens University Medical School, A Cardiology Department, Greece. tousouli@med.uoa.gr
Antoniades
Charalambos
C
Vassiliadou
Carmen
C
Toutouza
Marina
M
Pitsavos
Christos
C
Tentolouris
Costas
C
Trikas
Athanasios
A
Stefanadis
Christodoulos
C
D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*; D014664:Vasodilation / Q000187:drug effects; D014810:Vitamin E / Q000008:administration & dosage / Q000627:therapeutic use*
D000975:Antioxidants; D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D014810:Vitamin E; D000069059:Atorvastatin