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(Circulation. 2001;103:2144.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Metabolic Abnormalities Characteristic of Dysmetabolic Syndrome Predict the Development of Transplant Coronary Artery Disease

A Prospective Study

Hannah Valantine, MD; Peter Rickenbacker, MD; Mariska Kemna, MD; Sharon Hunt, MD; Y.-D. Ida Chen, PhD; Gerald Reaven, MD; Edward B. Stinson, MD

From the Division of Cardiovascular Medicine (H.V., P.R., M.K., S.H.), the Department of Cardiothoracic Surgery (E.B.S.), and the Division of Endocrinology, Gerontology, and Metabolism (Y.-D.I.C., G.R.), Stanford University, Stanford, Calif.

Correspondence to Hannah A. Valantine, MD, Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305-5246.

Background—This study examines the hypothesis that metabolic abnormalities of dysmetabolic syndrome are risk factors for transplant coronary artery disease (TxCAD).

Methods and Results—Sixty-six patients without overt diabetes, 2 to 4 years after surgery, underwent intracoronary ultrasound (ICUS), measurement of plasma glucose and insulin after oral glucose (75 g), and fasting lipid and lipoproteins. TxCAD incidence by angiography or autopsy was prospectively determined during subsequent follow-up (8 years). Coronary artery intimal thickness (IT) and subsequent outcomes were compared in patients stratified as having "high" versus "low" plasma glucose (>8.9 mmol/L) and insulin (>760 pmol/L) 2 hours after glucose challenge; and "abnormal" versus "normal" fasting lipid and lipoprotein concentrations as defined by the National Cholesterol Education Program. Patients with high glucose or insulin concentrations had greater IT: 0.38±0.05 versus 0.22±0.02 mm, P0.05, and 0.39±0.05 versus 0.20±0.02 mm, P0.01, respectively. Freedom from TxCAD was 56±11% versus 81±6% (P<0.01) in patients with high versus low glucose and 57±10% versus 82±7% (P<0.05) in patients with high versus low insulin. Actuarial survival was 60±12% versus 92±5% (P<0.005) in patients with high versus low glucose and 72±9% versus 88±6% (P<0.05) in patients with high versus low insulin. Triglycerides and VLDL were higher and HDL was lower in patients with IT >0.3 mm than with IT 0.3 mm. TxCAD incidence was higher in patients with high plasma TG and VLDL and low HDL.

Conclusions—These data suggest that insulin resistance plays a role in TxCAD.

Key Words: transplantation • atherosclerosis • insulin • hyperinsulinemia • hypertriglyceridemia

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