Osteoprotegerin concentrations in patients with suspected reversible myocardial ischemia: Observations from the Akershus Cardiac Examination (ACE) 1 Study

• During stress testing, OPG levels increased acutely regardless of MPI results.
• At baseline OPG was higher in patients referred for MPI than in healthy controls.
• OPG was associated with a history of CAD, but not with reversible ischemia.

Increased circulating osteoprotegerin (OPG) levels have been associated with the prevalence and severity of coronary artery disease and the risk of cardiovascular death. OPG is a cytokine of the tumor necrosis factor receptor superfamily and is expressed in various cell types in the body, including osteoblasts, inflammatory cells, vascular smooth muscle cells/endothelial cells and cardiomyocytes. The main sources determining OPG levels in the circulation however, are not well understood, and whether reversible myocardial ischemia influences OPG levels are not known. Accordingly, OPG levels were measured in 198 patients referred for exercise stress testing and myocardial perfusion imaging (MPI). In addition OPG levels were measured in 8 healthy control subjects performing a maximal bicycle stress test. Plasma samples were collected before, immediately after, 1.5 h and 4.5 h after exercise stress testing with MPI. OPG levels at baseline were not different in patient with reversible myocardial ischemia (n = 19) and patients without reversible ischemia (n = 179) (4.7 [3.6–5.5] pmol/L vs. 4.3 [3.4–5.2] pmol/L, p = 0.21), and there was an increase in OPG levels immediately after exercise regardless of whether or not the patient had reversible ischemia on MPI (absolute increase: 0.2 [0–0.55] pmol/L vs. 0.3 [0–0.5] pmol/L, p = 0.72). OPG levels also increased immediately after stress in the 8 control subjects (3.5 (3.2–3.8) pmol/L at baseline to 3.8 (3.5–4.7), p = 0.008). In conclusion, OPG levels increase acutely during exercise stress testing, but this increase is likely caused by mechanisms other than myocardial ischemia.