Circulating osteoprotegerin levels and long-term prognosis in patients with acute coronary syndromes

Reviewed by:
Ijaz A. Khan, MD, FCCP
Steering Committee Member, Cardiovascular Medicine and Surgery NetWork
Good Samaritan Hospital, Baltimore, MD

Omland T, Ueland T, Jansson AM, et al. Circulating osteoprotegerin levels and long-term prognosis in patients with acute coronary syndromes. J Am Coll Cardiol 2008; 51:627- 633

This study tested the hypothesis that serum osteoprotegerin levels on admission are associated with long-term prognosis in patients with acute coronary syndrome. The study population consisted of 897 patients with acute coronary syndrome with a median age of 66 years. The primary outcome measure was all-cause mortality. The serum osteoprotegerin levels were drawn within 24 h of admission. Analyses were performed to determine the association between serum osteoprotegerin levels and incidence of death, hospitalization due to heart failure, myocardial infarction, and stroke. The median patient follow-up was at 89 months. A total of 261 patients died during the follow-up period. The baseline osteoprotegerin level was associated with increased long-term mortality, hospitalization due to heart failure, and recurrent myocardial infarction. After adjustment for conventional risk markers, including troponin I level, C-reactive protein level, B-type natriuretic peptide level, and ejection fraction, the association remained significant for mortality and hospitalization due to heart failure but not for recurrent myocardial infarction. As a predictor of mortality, serum osteoprotegerin levels performed similarly to Btype natriuretic peptide levels and left ventricular ejection fraction, but better than C-reactive protein levels and cardiac troponin I levels. The study concluded that the serum osteoprotegerin level is a strong predictor of long-term mortality and development of heart failure in patients with acute coronary syndrome independent of the conventional risk markers.

Osteoprotegerin is a member of the tumor necrosis factor receptor superfamily. It has pleiotropic effects on bone metabolism, endocrine function, and the immune system. Osteoprotegerin has been linked to inflammatory responses and atherosclerosis. In humans, elevated serum concentrations have been associated with aortic plaques, coronary artery disease, cerebrovascular disease, and peripheral vascular disease. Circulating osteoprotegerin levels are increased in patients presenting with acute coronary syndrome. Authors in this study tested if serum level of osteoprotegerin measured in patients with acute coronary syndrome carries a long-term prognostic value, and they found that it is a strong predictor of long-term mortality and development of heart failure in such patients.

The strengths of the study include large sample size, prospective design, and long duration of follow-up. The weaknesses are lack of data on cardiovascular mortality and single measurement of cardiovascular biomarkers. The serial measurements of cardiovascular biomarkers would have been parallel to the clinical practice because, after all, the results of any study, if substantiated, have to be used in clinical practice. In summary, the circulating osteoprotegerin levels may become a useful prognostic marker in patients with acute coronary syndrome but needs further testing to attain the status of left ventricle ejection fraction, cardiac troponin levels, and B-type natriuretic peptide levels. Until then, clinicians should continue relying on these time-tested markers of long-term prognosis after acute coronary syndrome.