Osteoprotegerin linked to worse prognosis in heart disease

Higher levels of osteoprotegerin is associated with increased risk of premature death in patients with chronic heart failure, and increased risk of cardiovascular death in patients with acute coronary syndromes.

Circulating osteoprotegerin levels is strongly linked to increased 30 day and one year risk of cardiovascular mortality in patients with NSTEMI or unstable angina pectoris. In her research, Ragnhild Røysland has also found an independent association between osteoprotegerin and premature death in patients with chronic heart failure. However, the clinical utility of osteoprotegerin as a prognostic biomarker in heart failure seems to be limited.

The article on acute coronary syndromes includes almost 4,500 patients included in the American MERLIN-TIMI 36 trial. During the one year follow-up, 208 patients died from cardiovascular causes. The risk was higher in patients with higher levels of circulating osteoprotegerin, also after statistical adjustments for other risk markers. Furthermore, adding high levels of osteoprotegerin to a risk marker model resulted in significantly improved reclassification of patients. Circulating osteoprotegerin was also independently associated with increased risk of heart failure during follow-up, but not new acute myocardial infarction.

1,229 patients from the Italian GISSI-HF study were included in the study that investigated osteoprotegerin as a risk marker in chronic heart failure. Røysland and colleagues found an independent association between higher levels and increased risk of death during follow-up, but adding osteoprotegerin to known risk markers did not significantly improve reclassification.

The PhD thesis also shows higher levels of osteoprotegerin in patients hospitalized for acute dyspnea because of heart failure than in patients with acute dyspnea because of lung disease. However, when controlling for relevant covariates, this difference disappeared. Also, osteoprotegerin does not seem to be increased in patients with reversible myocardial ischemia, but levels increase during exercise stress testing in both patients and healthy controls.


Thesis: Circulating osteoprotegerin as a biomarker in coronary heart disease and heart failure
 Ragnhild Røysland
Time and place: March 30, 2017, Akershus University Hospital, Lørenskog


Røysland, R., Masson, S., Omland, T., Milani, V., Bjerre, M., Flyvbjerg, A., di Tano, G., Misuraca, G., Maggioni, A. P., Tognoni, G., Tavazzi, L., & Latini, R. (2010). Prognostic value of osteoprotegerin in chronic heart failure: The GISSI-HF trial. American heart journal, 160(2), 286-293.

Røysland, R., Bonaca, M. P., Omland, T., Sabatine, M., Murphy, S. A., Scirica, B. M., Bjerre, M., Flyvberg, A., Braunwald, E., & Morrow, D. A. (2012). Osteoprotegerin and cardiovascular mortality in patients with non-ST elevation acute coronary syndromes. Heart, 98(10), 786-791.

Røysland, R., Røsjø, H., Høiseth, A. D., Gullestad, L., Badr, P., Kravdal, G., & Omland, T. (2015). Osteoprotegerin concentrations in patients with suspected reversible myocardial ischemia: Observations from the Akershus Cardiac Examination (ACE) 1 Study. Cytokine, 73(1), 122-127.

Røysland, R., Pervez, M. O., Pedersen, M. H., Brynildsen, J., Høiseth, A. D., Hagve, T. A., Røsjø, H., & Omland, T. (2016). Diagnostic and Prognostic Properties of Osteoprotegerin in Patients with Acute Dyspnoea: Observations from the Akershus Cardiac Examination (ACE) 2 Study. PloS one, 11(7), e0160182.

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