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(Circulation. 2008;117:2123-2130.)
© 2008 American Heart Association, Inc.

Vascular Medicine

Increased High-Density Lipoprotein Cholesterol Predicts the Pioglitazone-Mediated Reduction of Carotid Intima-Media Thickness Progression in Patients With Type 2 Diabetes Mellitus

Michael Davidson, MD; Peter M. Meyer, PhD; Steven Haffner, MD; Steven Feinstein, MD; Ralph D’Agostino, Sr, PhD; George T. Kondos, MD; Alfonso Perez, MD; Zhen Chen, MS; Theodore Mazzone, MD

From the Pritzker School of Medicine (M.D.), The University of Chicago, Chicago, Ill; Department of Preventive Medicine (P.M.M., Z.C.) and Department of Medicine, Section of Cardiology (S.F.), Rush University Medical Center, Chicago, Ill; Department of Medicine, University of Texas Health Science Center (S.H.), San Antonio, Tex; Department of Mathematics (R.D.), Statistics and Consulting Unit, Boston University, Boston, Mass; Department of Medicine (T.M.) and Department of Medicine, Section of Cardiology (G.T.K.), University of Illinois College of Medicine, Chicago, Ill; and Takeda Global Research and Development, Ltd (A.P.), Deerfield, Ill.

Correspondence to Theodore Mazzone, MD, Section of Endocrinology, Diabetes and Metabolism (MC 797), University of Illinois at Chicago, 1819 W Polk St, Chicago, IL 60612. E-mail tmazzone{at}uic.edu

Received October 16, 2007; accepted February 20, 2008.

Background— Measurement of carotid intima-media thickness (CIMT) has been validated as a measure of atherosclerosis and as a predictor of future cardiovascular events. Compared with glimepiride, pioglitazone has been shown to slow the progression of atherosclerosis measured by CIMT in patients with type 2 diabetes mellitus.

Methods and Results— We evaluated individual cardiovascular risk factors as predictors of the change in CIMT produced by pioglitazone treatment by determining whether their addition to a baseline model resulted in loss of significance for the treatment effect on CIMT. Pioglitazone treatment led to improvement in levels of multiple cardiovascular risk markers, including high-sensitivity C-reactive protein, apolipoprotein B, apolipoprotein A1, high-density lipoprotein (HDL) cholesterol, triglyceride, insulin, and free fatty acid. At 24 weeks, there were significant differences in HDL cholesterol, triglyceride, total cholesterol, low-density lipoprotein cholesterol, insulin, body mass index, hip circumference, and high-sensitivity C-reactive protein between the pioglitazone and glimepiride treatment groups. After adjustment for 24-week on-treatment values of cardiovascular risk factors, only inclusion of the changes in HDL cholesterol and insulin significantly impacted the magnitude and significance of the treatment effect on CIMT. Furthermore, irrespective of treatment assignment, increased HDL cholesterol at 24 weeks was a significant predictor of reduced CIMT progression at 72 weeks.

Conclusions— The beneficial effect of pioglitazone on HDL cholesterol at 24 weeks predicted its beneficial effect for reducing CIMT progression at 72 weeks. Changes in HDL cholesterol at 24 weeks, irrespective of treatment, predicted less progression of CIMT at 72 weeks. These results suggest that suppression of atherosclerosis with pioglitazone therapy is linked to its ability to raise HDL cholesterol.

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CLINICAL PERSPECTIVE

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Clinical Summaries
Circulation 2008 117: 2041. [Extract] [Full Text]

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