Published online before print March 15, 2004, doi: 10.1161/01.CIR.0000124716.67921.D2
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(Circulation. 2004;109:1724-1728.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Pregnancy-Associated Plasma Protein A and Its Endogenous Inhibitor, the Proform of Eosinophil Major Basic Protein (proMBP), Are Related to Complex Stenosis Morphology in Patients With Stable Angina Pectoris
From the Department of Cardiac and Vascular Sciences (J.C.-S., P.K., D.C., D.W.H., J.C.K.), St George’s Hospital Medical School, London, UK; Department of Clinical Biochemistry (M.C.), Statens Serum Institut, Copenhagen, Denmark; Copenhagen Heart Arrhythmia Research Center (M.C.), Copenhagen, Denmark; and Department of Molecular Biology (C.O., M.T.O.), Science Park, University of Aarhus, Aarhus, Denmark.
Correspondence to Prof J.C. Kaski, Head, Cardiological Sciences, Department of Cardiac and Vascular Sciences, St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. E-mail jkaski{at}sghms.ac.uk
Received August 22, 2003; de novo received December 9, 2003; accepted January 28, 2004.
Background— The metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) has been implicated in coronary plaque disruption. Its endogenous inhibitor, the proform of eosinophil major basic protein (proMBP), may also play a role in this process. Atheromatous plaque disruption often presents as complex angiographic lesions. We sought to assess whether PAPP-A, proMBP, and PAPP-A/ProMBP ratio are markers of angiographic plaque complexity in patients with chronic stable angina.
Methods and Results— We studied 396 stable angina patients (age 63±10 years, 230 men) of whom 289 had angiographically documented coronary artery disease (
75% stenosis). All coronary stenoses 30% diameter reduction (n =531 in 322 patients) were assessed and classified as complex (n =228) or smooth (n =303) by previously validated criteria. PAPP-A, proMBP, and C-reactive protein (hs-CRP) serum levels were measured by ELISA. Patients with complex coronary stenoses had a significantly (P<0.001) higher PAPP-A/proMBP ratio (3.1±1.2 versus 2.7±0.8x10–3) and PAPP-A levels (5.9±1.6 versus 5.1±1.4 mIU/L) than those without. On univariate analysis, male gender (P<0.001), age (P<0.001), previous history of myocardial infarction (P=0.013), reduced ejection fraction (P<0.001), severe coronary artery disease (P<0.001), aspirin treatment (P<0.001), PAPP-A levels (P<0.001), and PAPP-A/proMBP ratio (P<0.001) were correlated with the number of complex stenoses. Multiple regression analysis showed that male gender, age, severe coronary artery disease, and PAPP-A/proMBP ratio were independent predictors of the number of angiographically complex stenoses.
Conclusions— In patients with stable angina, PAPP-A and PAPP-A/proMBP ratio are associated with angiographic plaque complexity.
Key Words: atherosclerosis • coronary disease • plaque complexity • metalloproteinases
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