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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:624.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Effects of Rosiglitazone on Lipids, Adipokines, and Inflammatory Markers in Nondiabetic Patients With Low High-Density Lipoprotein Cholesterol and Metabolic Syndrome

Frederick F. Samaha; Philippe O. Szapary; Nayyar Iqbal; Monica M. Williams; LeAnne T. Bloedon; Arshneel Kochar; Megan L. Wolfe; Daniel J. Rader

From the Department of Medicine (F.F.S., P.O.S., M.M.W., A.K., D.J.R.), Cardiovascular Division, and the Cardiovascular Institute, University of Pennsylvania Medical Center; The Philadelphia Veterans Affairs Medical Center (F.F.S., N.I., M.M.W.); The Institute for Translational Medicine and Therapeutics (F.F.S., P.O.S., L.T.B., M.L.W., D.J.R.), University of Pennsylvania, Philadelphia. Current affiliation for P.O.S. is Wyeth Research, Collegeville, Pa.

Correspondence to Frederick F. Samaha, Philadelphia VA Medical Center, University and Woodland Avenue, Philadelphia, PA 19104. E-mail rick.samaha{at}med.va.gov

Background— PPAR- agonists improve insulin sensitivity and glycemic control in type 2 diabetes and may reduce atherosclerosis progression. Thus, PPAR- agonists may be an effective therapy for metabolic syndrome. However, the full spectrum of potentially antiatherogenic mechanisms of PPAR- agonists have not been fully tested in nondiabetic patients with metabolic syndrome.

Methods and Results— We performed a prospective, double-blinded, placebo-controlled study of 60 nondiabetic subjects with low high-density lipoprotein cholesterol (HDL-C) level and metabolic syndrome to rosiglitazone 8 mg daily or placebo for 12 weeks. We found no significant effect of rosiglitazone on HDL-C (+5.5% versus +5.8%, P=0.89), and an increase in total cholesterol (+8% versus –1%; P=0.03). Nevertheless, rosiglitazone significantly increased adiponectin (+168% versus +25%; P<0.001), and lowered resistin (–6% versus +4%; P=0.009), C-reactive protein (–32% versus +36%, P=0.002), interleukin (IL)-6 (–22% versus +4%, P<0.001), and soluble tumor-necrosis factor- receptor-2 (–5% versus +7%, P<0.001).

Conclusions— These findings suggest that rosiglitazone, presumably through its PPAR- agonist properties, has direct effects on inflammatory markers and adipokines in the absence of favorable lipid effects. These findings may help explain the mechanism underlying the possible antiatherosclerotic effects of rosiglitazone.

We performed a 12-week, prospective, double-blinded study of 60 nondiabetic subjects with metabolic syndrome randomized to rosiglitazone or placebo. Rosiglitazone had direct effects on inflammatory markers and adipokines in the absence of favorable lipid effects. These findings may underly the possible antiatherosclerotic effects of rosiglitazone.

Key Words: adipocytokines • lipids • inflammation • lipoprotein metabolism • arteriosclerosis

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