Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: Results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (Island) Study

• Published in: Circulation (New York, N.Y.) N.Y.), 2005-01, Vol.111 (3), p.343-348
• Main Authors: SOLA, Srikanth, MIR, Muhammad Q. S, CHEEMA, Faiz A, KHAN-MERCHANT, Nadya, MENON, Rekha G, PARTHASARATHY, Sampath, KHAN, Bobby V
• Format: Article
• Language: English
• Subjects: Adult; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Antioxidants - therapeutic use; Biological and medical sciences; Biomarkers - blood; Biphenyl Compounds - therapeutic use; Blood and lymphatic vessels; Brachial Artery - drug effects; Brachial Artery - physiopathology; Cardiology. Vascular system; Dietary Supplements; Dinoprost - analogs & derivatives; Dinoprost - blood; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Female; Humans; Inflammation - drug therapy; Inflammation - metabolism; Interleukin-6 - blood; Male; Medical sciences; Metabolic Syndrome - physiopathology; Middle Aged; Plasminogen Activator Inhibitor 1 - blood; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Tetrazoles - therapeutic use; Thioctic Acid - therapeutic use; Vasodilation - drug effects
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000153272.48711.B9

The metabolic syndrome is associated with increased angiotensin II activity, induction of a proinflammatory and oxidative state, and endothelial dysfunction. We evaluated the ability of irbesartan, an angiotensin receptor blocker, and lipoic acid, an antioxidant, to affect endothelial function and inflammation in patients with the metabolic syndrome. We randomized 58 subjects with the metabolic syndrome in a double-blinded manner to irbesartan 150 mg/d (n=14), lipoic acid 300 mg/d (n=15), both irbesartan and lipoic acid (n=15), or matching placebo (n=14) for 4 weeks. Endothelium-dependent and -independent flow-mediated vasodilation was determined under standard conditions. Plasma levels of interleukin-6, plasminogen activator-1, and 8-isoprostane were measured. After 4 weeks of therapy, endothelium-dependent flow-mediated vasodilation of the brachial artery was increased by 67%, 44%, and 75% in the irbesartan, lipoic acid, and irbesartan plus lipoic acid groups, respectively, compared with the placebo group. Treatment with irbesartan and/or lipoic acid was associated with statistically significant reductions in plasma levels of interleukin-6 and plasminogen activator-1. In addition, treatment with irbesartan or irbesartan plus lipoic acid decreased 8-isoprostane levels. No significant changes in blood pressure were noted in any of the study groups. Administration of irbesartan and/or lipoic acid to patients with the metabolic syndrome improves endothelial function and reduces proinflammatory markers, factors that are implicated in the pathogenesis of atherosclerosis.