Osteoprotegerin and coronary artery disease in type 2 diabetic patients with microalbuminuria

Henrik Reinhard,Peter R Hansen,Lars M Rasmussen,Niels Wiinberg,Mads Nybo,Kaj Winther,Peter K Jacobsen,Hans-Henrik Parving,Peter Rossing,Claus L Petersen,Andreas Kjær

doi:10.1186/1475-2840-10-70

Abstract

ObjectivePlasma osteoprotegerin (P-OPG) is an independent predictor of cardiovascular disease in diabetic and other populations. OPG is a bone-related glycopeptide produced by vascular smooth muscle cells and increased P-OPG may reflect arterial damage. We investigated the correlation between P-OPG and coronary artery disease (CAD) in asymptomatic type 2 diabetic patients with microalbuminuria.MethodsP-OPG was measured in 200 asymptomatic diabetic patients without known cardiac disease. Patients with P-NT-proBNP >45.2 ng/l and/or coronary calcium score (CCS) ≥400 were stratified as high risk of CAD (n = 133), and all other patients as low risk patients (n = 67). High risk patients were examined by myocardial perfusion imaging (MPI; n = 109), and/or CT-angiography (n = 20), and/or coronary angiography (CAG; n = 86). Significant CAD was defined by presence of significant myocardial perfusion defects at MPI and/or >70% coronary artery stenosis at CAG.ResultsSignificant CAD was demonstrated in 70 of the high risk patients and of these 23 patients had >70% coronary artery stenosis at CAG. Among high risk patients, increased P-OPG was an independent predictor of significant CAD (adjusted odds ratio [CI] 3.11 [1.01-19.54] and 3.03 [1.00-9.18] for second and third tertile vs.first tertile P-OPG, respectively) and remained so after adjustments for NT-proBNP and CCS. High P-OPG was also associated with presence of >70% coronary artery stenosis(adjusted odds ratio 14.20 [1.35-148.92] for third vs. first tertile P-OPG), and 91% of patients with low (first tertile) P-OPG did not have >70% coronary artery stenosis.ConclusionsElevated P-OPG is an independent predictor of the presence of CAD in asymptomatic type 2 diabetic patients with microalbuminuria.

Highlights

Coronary artery disease (CAD) is the most important determinant of the excessive morbidity and mortality in type 2 diabetic patients, especially in patients with albuminuria[1]
Osteoprotegerin is a member of the tumor necrosis factor (TNF) receptor superfamily acting as a soluble decoy receptor for the receptor activator of nuclear factor-b ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL) preventing osteoclast activation and bone resorption, and participating in
Patient cohort and investigations In a cross-sectional study at Steno Diabetes Center, we identified from January 2007 to February 2008 a consecutive cohort of 200 type 2 diabetic patients with microalbuminuria but without prior heart disease and with normal P-creatinine

Summary

Introduction

Coronary artery disease (CAD) is the most important determinant of the excessive morbidity and mortality in type 2 diabetic patients, especially in patients with albuminuria[1]. Plasma osteoprotegerin (P-OPG) is a promising predictor of cardiovascular disease (CVD) in high risk diabetic populations, as well as in other populations [2,3,4,5]. Osteoprotegerin is a member of the tumor necrosis factor (TNF) receptor superfamily acting as a soluble decoy receptor for the receptor activator of nuclear factor-b ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL) preventing osteoclast activation and bone resorption, and participating in mortality in type 2 diabetic patients in a study with 17 years of follow-up[3]. We evaluated if P-OPG could serve as a biomarker for subclinical CAD in asymptomatic type 2 diabetic patients with microalbuminuria

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