Circulation. 2003;107:1954-1957
Published online before print April 14, 2003, doi: 10.1161/01.CIR.0000069272.06194.91
Published online before print April 14, 2003, doi: 10.1161/01.CIR.0000069272.06194.91
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(Circulation. 2003;107:1954.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
Effect of Rosiglitazone Treatment on Soluble CD40L in Patients With Type 2 Diabetes and Coronary Artery Disease
From the Department of Internal Medicine II–Cardiology (N.M., A.I., J.F., L.S., J.I., V.H., W.K.), University of Ulm, Hospital of Heidenheim (G.W., A.S.), Teaching Hospital of the University of Ulm, and the Department of Clinical Chemistry (W.M.), University of Freiburg, Germany.
Correspondence to Nikolaus Marx, MD, Department of Internal Medicine II–Cardiology, University of Ulm, Robert-Koch-Str. 8, D-89081 Ulm, Germany. E-mail nikolaus.marx{at}medizin.uni-ulm.de
Background— Interaction of CD40L with its receptor CD40 is critically involved in inflammatory cell activation in atherogenesis. In addition, serum levels of soluble CD40L are elevated in acute coronary syndromes and have been associated with increased cardiovascular risk in healthy subjects, thus making sCD40L an intriguing target to modulate the inflammatory response in the vasculature. PPAR
-activating thiazolidinediones, novel insulin-sensitizing antidiabetic agents, have recently been shown to exhibit antiinflammatory effects in the vessel wall. To examine whether thiazolidinedione treatment might modulate serum levels of sCD40L in high-risk patients, we performed a randomized, placebo-controlled, single-blinded trial to assess the effect of rosiglitazone on sCD40L levels in patients with type 2 diabetes and coronary artery disease (CAD).
Methods and Results— Thirty-nine patients with diabetes and angiographically proven CAD were randomized to receive rosiglitazone (4 mg BID) or placebo for 12 weeks. Baseline parameters did not significantly differ between groups. Rosiglitazone treatment, but not placebo, significantly reduced sCD40L serum levels within the first 2 weeks by 8.1% (17.1 to -32.7) (median percentage [interquartile range]; P<0.05 compared with baseline), further decreasing it by 18.4% (-5.0 to -33.1) after 6 weeks (P<0.05 compared with baseline), and by 27.5% (8.2 to -70.5) after 12 weeks (P<0.05 compared with baseline and with 2 weeks of treatment).
Conclusion— Treatment with the PPAR-activating thiazolidinedione rosiglitazone reduces sCD40L serum levels in patients with type 2 diabetes and CAD. These data support an antiinflammatory and potentially antiatherogenic effect of thiazolidinediones.
Key Words: diabetes mellitus • coronary disease • receptors
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