Osteoprotegerin Is Associated With Silent Coronary Artery Disease in High-Risk but Asymptomatic Type 2 Diabetic Patients

Abstract

OBJECTIVE—Osteoprotegerin (OPG) is an inhibitor of osteoclastogenesis, which has been recently involved in atherosclerosis. The relationship between coronary atherosclerosis and OPG has never been studied in asymptomatic type 2 diabetic patients. RESEARCH DESIGN AND METHODS—This is a nested case-control study; 162 asymptomatic type 2 diabetic patients were evaluated for silent myocardial ischemia using stress myocardial perfusion imaging; of 50 patients with positive results, 37 underwent coronary angiography, 20 of whom showed significant coronary artery disease (CAD group). Of 112 patients without silent myocardial ischemia, 20 subjects (NO-CAD group) were selected and matched by age and sex to patients with CAD. OPG, C-reactive protein, adiponectin, lipoprotein(a), albuminuria, and classical risk factors were measured. RESULTS—The percentages of subjects with OPG levels above median and with nephropathy were higher in the CAD group than in the NO-CAD group (70 vs. 25%, P = 0.004 and 50 vs. 5%, P = 0.001, respectively). LDL cholesterol levels were higher and HDL cholesterol levels lower in the CAD compared with the NO-CAD group (P = 0.033 and P = 0.005, respectively). No other variables were associated with CAD. Logistic regression analysis showed that OPG values above median (odds ratio 8.31 [95% CI 1.18–58.68], P = 0.034) and nephropathy (21.98 [1.24–388.36], P = 0.035) were significant independent predictors of asymptomatic CAD in type 2 diabetic patients. CONCLUSIONS—Our investigation reports the first evidence of an independent association of OPG with asymptomatic CAD in type 2 diabetic patients. The results of this nested case- control study with 20 cases need to be confirmed in a larger population.