Addition of Losartan to Angiotensin-Converting Enzyme Inhibitors Improves Insulin Resistance in Patients With Chronic Heart Failure Treated Without β-Blockers

• Published in: Circulation Journal Vol. 74; no. 11; pp. 2346 - 2352
• Main Authors: Ogino, Kazuhide, Kato, Masahiko, Furuse, Yoshiyuki, Kinugasa, Yoshiharu, Kaetsu, Yasuhiro, Mizuta, Einosuke, Sugihara, Shinobu, Ishida, Katsunori, Yanagihara, Kiyotaka, Hisatome, Ichiro, Shigemasa, Chiaki
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 01.11.2010
• Subjects: Adrenergic beta-Antagonists - therapeutic use; Aged; Angiotensin; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Biomarkers - blood; Blood Glucose - metabolism; Chemokine CCL2 - blood; Chronic Disease; Cross-Over Studies; Cytokine; Drug Therapy, Combination; Enalapril - therapeutic use; Female; Heart failure; Heart Failure - blood; Heart Failure - drug therapy; Heart Failure - physiopathology; Humans; Imidazolidines - therapeutic use; Inflammation; Inflammation Mediators - blood; Insulin; Insulin - blood; Insulin Resistance; Interleukin-6 - blood; Japan; Lisinopril - therapeutic use; Losartan - therapeutic use; Male; Middle Aged; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha - blood; Japan
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.CJ-10-0395

Background: Angiotensin II and insulin resistance (IR) have clinical implications in the pathophysiology of chronic heart failure (CHF). However, it is still unclear whether the combination of an angiotensin-receptor blocker and angiotensin-converting enzyme inhibitor (ACEI) improves IR in CHF patients who do not receive β-blockers. Thus, the aim of the present study was to evaluate the effects of losartan on glucose metabolism and inflammatory cytokines in CHF patients treated with ACEI but not β-blockers. Methods and Results: The effect of losartan treatment for 16 weeks on IR was analyzed in 16 CHF patients in a randomized crossover trial. Insulin level and homeostasis model IR index (HOMA-IR) decreased significantly (P<0.05), but fasting plasma glucose did not change significantly. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 levels were significantly decreased with losartan (P<0.05). Furthermore, the changes in IL-6 and MCP-1 levels were significantly correlated with the reduction in HOMA-IR (P<0.05), but the change in TNF-α levels was not significantly correlated. Conclusions: The addition of losartan to ACEI therapy improved IR and decreased inflammatory cytokines in CHF patients who did not receive β-blockers. (Circ J 2010; 74: 2346-2352)