Pioglitazone produces rapid and persistent reduction of vascular inflammation in patients with hypertension and type 2 diabetes mellitus who are receiving angiotensin II receptor blockers.
Inhibition of the renin-angiotensin system reportedly exerts potent antiatherogenic effects by reducing vascular inflammation. We tested the hypothesis that pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, further reduces vascular inflammation in patients receiving angiotensin II receptor blockers. Patients with hypertension who had developed type 2 diabetes mellitus were randomly assigned to receive either pioglitazone (15 mg/d, n = 20) or voglibose, an alpha-glucosidase inhibitor (0.6 mg/d, n=19) for 6 months, and changes in their serum concentrations of C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were monitored. Pioglitazone, but not voglibose, reduced CRP levels within 1 month (-51%+/-7%, mean+/-SEM; P<.001). C-reactive protein levels were decreased after 6 months of treatment with either pioglitazone or voglibose, with the former being more effective (-57%+/-8% vs -9%+/-18%; P<.05). The levels of ICAM-1 and VCAM-1 were significantly reduced after 1 month of pioglitazone therapy (-9%+/-3% and -8%+/-3%, respectively; both P<.05), with the beneficial effects persisting throughout the study period. In contrast, the levels of ICAM-1 and VCAM-1 were not altered during the study period in patients on voglibose. There was no correlation between the reduction of hemoglobin A1c and that of CRP, ICAM-1, or VCAM-1. These results suggest that augmentation with pioglitazone further reduces vascular inflammation in patients with hypertension and diabetes who are receiving angiotensin II receptor blockers. This may contribute to the reduction of cardiovascular events in this at-risk population.
Takase
Hiroyuki
H
Department of Internal Medicine, Enshu General Hospital, Hamamatsu 430-0917, and Internal Medicine and Molecular Science, Graduate School of Medical Sciences, Nagoya City University, Japan.
Nakazawa
Ai
A
Yamashita
Sumiyo
S
Toriyama
Takayuki
T
Sato
Koichi
K
Ueda
Ryuzo
R
Dohi
Yasuaki
Y
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000150:complications*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014657:Vasculitis / Q000150:complications*
D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone