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(Circulation. 2004;110:803-809.)
© 2004 American Heart Association, Inc.

Original Articles

Measures of Insulin Resistance Add Incremental Value to the Clinical Diagnosis of Metabolic Syndrome in Association With Coronary Atherosclerosis

Muredach P. Reilly, MB; Megan L. Wolfe, BS; Thomas Rhodes, MSPH; Cynthia Girman, DrPH; Nehal Mehta, MD; Daniel J. Rader, MD

From the Cardiovascular Division and Center for Experimental Therapeutics, Department of Medicine, University of Pennsylvania School of Medicine (M.P.R., M.L.W., N.M., D.J.R.), and the Department of Epidemiology, Merck Research Laboratories (T.R., C.G.), Philadelphia, Pa.

Correspondence to Muredach Reilly, Cardiovascular Division, University of Pennsylvania Medical Center, 909 BRB 2/3, 421 Curie Blvd, Philadelphia, PA 19104-6160. E-mail muredach{at}spirit.gcrc.upenn.edu

Received December 23, 2003; revision received April 1, 2004; accepted April 4, 2004.

Background— Whether measures of insulin resistance provide incremental information regarding atherosclerotic cardiovascular disease beyond current National Cholesterol Education Program (NCEP) Adult Treatment Panel III metabolic syndrome (MetSyn) criteria or inflammatory markers is uncertain.

Methods and Results— We examined the association of insulin resistance and MetSyn with coronary artery calcification (CAC) in 840 asymptomatic nondiabetic subjects. Both NCEP and World Health Organization–defined MetSyn were associated (ordinal regression odds ratio [OR] and 95% confidence intervals for NCEP-defined MetSyn) with CAC after controlling for age, non-MetSyn risk factors, and plasma CRP levels (OR, 1.93 [1.43 to 2.60], P<0.001) and after further controlling for homeostasis model assessment index (HOMA) (OR, 1.56 [1.14 to 2.15], P=0.006). Conversely, HOMA was significantly associated with CAC after adjusting for age, non-MetSyn risk factors, and CRP levels (OR, 1.62 [1.31 to 2.01], P<0.001) and after further adjusting for NCEP-defined MetSyn (OR, 1.45 [1.16 to 1.82], P=0.007). Addition of HOMA to the NCEP MetSyn significantly improved the association with CAC, but addition of CRP data to MetSyn or HOMA did not.

Conclusions— Both MetSyn and HOMA index were associated with coronary atherosclerosis independent of established risk factors, including CRP. These findings support the use of biomarkers of insulin resistance in addition to NCEP MetSyn criteria in assessing cardiovascular disease risk.

Key Words: metabolism • insulin • atherosclerosis

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