Pioglitazone improves endothelial function in non-diabetic patients with coronary artery disease.
OBJECTIVE
To test the hypothesis that pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, will improve endothelial function in non-diabetic subjects with coronary artery disease, we conducted a prospective study to evaluate the effect of this medication on the brachial artery vasomotor function and circulating markers of endothelial activation.


METHODS
Baseline characteristics were collected. After initial endothelial function assessment, patients were treated with pioglitazone hydrochloride 30 mg daily. The medication was continued for 12 weeks and endothelial function was reassessed as well as the inflammatory markers. The study medication then was stopped, and all the tests were repeated 12 weeks later.


RESULTS
Seventeen subjects completed all three-study phases. Mean age was 58 (range: 36-77 years). Compared with the baseline, the endothelium-dependent vasodilation improved significantly with the treatment (p < 0.001) from 4.4 +/- 3.9 to 8.4 +/- 4.1%, a relative increase of 91%. After withdrawal of treatment, the endothelium-dependent vasodilation returned towards baseline values. There was no change in endothelium-independent vasodilatation (12.27 +/- 6.35 to 13.9 +/- 9.23%, to 12.42 +/- 5.35%, p = 0.177). The urine asymmetric dimethlyarginine levels decreased significantly with the treatment, but also returned to the initial values after the wash-out period (1.27 +/- 0.5 micromol/ml to 0.97 +/- 0.3 micromol/ml to 1.34 +/- 0.5 micromol/ml, p = 0.017). No difference in the lipid profile, C-reactive protein, erythrocyte sedimentation rate, or fibrinogen levels was seen.


CONCLUSIONS
Pioglitazone rapidly improves endothelial function in non-diabetic patients with coronary artery disease. This improvement is associated with a change in mean urinary asymmetric dimethylarginine levels, although a cause and effect cannot be determined from this investigation.
Staniloae
C
C
St. Vincent Medical Center Manhattan, New York, NY 10011, USA. cstaniloae@aol.com
Mandadi
V
V
Kurian
D
D
Coppola
J
J
Bernaski
E
E
El-Khally
Z
Z
Morlote
M
M
Pinassi
E
E
Ambrose
J
J
D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000652:urine; D001799:Blood Sedimentation; D001916:Brachial Artery / Q000187:drug effects* / Q000503:physiopathology; D002097:C-Reactive Protein / Q000032:analysis; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists; D000077205:Pioglitazone; D011446:Prospective Studies; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
D002317:Cardiovascular Agents; D008055:Lipids; D047495:PPAR gamma; D045162:Thiazolidinediones; C018524:N,N-dimethylarginine; D005340:Fibrinogen; D002097:C-Reactive Protein; D001120:Arginine; D000077205:Pioglitazone