Osteoprotegerin: A Novel Independent Marker for Silent Myocardial Ischemia in Asymptomatic Diabetic Patients

Abstract

OBJECTIVE—We sought to evaluate osteoprotegerin, an inhibitor of osteoclastogenesis involved in atherosclerosis, and other novel risk factors as predictive markers of silent myocardial ischemia (SMI). RESEARCH DESIGN AND METHODS—A total of 465 consecutive diabetic patients with more than one additional risk factor were evaluated for SMI using stress myocardial perfusion imaging (MPI). We studied the association of SMI (positive stress electrocardiogram and/or abnormal MPI) with osteoprotegerin, other novel risk factors (lipoprotein[a], homocysteine, adiponectin, C-reactive protein, and fibrinogen), and conventional risk factors (total, LDL, and HDL cholesterol and triglycerides). RESULTS—A total of 92 patients were diagnosed with SMI. Of the six novel markers, osteoprotegerin was the only one associated with SMI; the relative risk (RR) of SMI in patients with osteoprotegerin values above the 75th percentile was 3.19 (95% CI 1.99–5.18; P < 0.001) in comparison with those with osteoprotegerin below the 75th percentile. In univariate analyses, the other plasma markers significantly associated with SMI were higher triglycerides (P = 0.04) and lower HDL cholesterol (P = 0.02). The association of osteoprotegerin with SMI remained significant after correcting for other variables associated with SMI at P < 0.15 in univariate analysis (RR 3.95 [95% CI 2.21–7.06]; P < 0.0001). The association of osteoprotegerin with SMI was observed in male (P < 0.0001) and female (P = 0.03) patients, in type 1 (P = 0.002) and type 2 (P = 0.0004) diabetic patients, in patients with (P = 0.0004) or without (P = 0.03) nephropathy, and in patients without (P < 0.0001) but not with (P = 0.2) peripheral arterial disease. CONCLUSIONS—Osteoprotegerin measurement, together with other conventional factors, can help to better define the diabetic population with an increased likelihood for SMI.