A study published in this issue of Heart explores the associations between plasma osteoprotegerin (OPG) collected within 48 h of the onset of symptoms of a non-ST elevation acute coronary syndrome (NSTE-ACS) and 30 day and 1 year incidence of cardiovascular death.1 A strong association was observed between OPG and cardiovascular mortality, and baseline OPG was also an independent predictor of new or worsening heart failure (HF).

The results of this study broaden our knowledge of the association between baseline OPG and cardiovascular outcomes in patients with NSTE-ACS and indicate that OPG is a strong independent predictor of death and hospitalisation for HF. The most interesting finding of this investigation is the evidence that HF, and not myocardial ischaemia or arrhythmias, is the main determinant of the association between OPG levels and cardiovascular death. This observation supports the hypothesis that the OPG system may be directly involved in the development and progression of HF, even though the biological mechanisms remain largely unknown. Whether OPG is simply a marker of the extent of myocardial damage and/or whether it participates in the onset and progression of HF remains to be elucidated.

OPG is a 401 amino acid glycoprotein discovered in 1997 by Simonet et al during a series of experiments designed to elucidate the role of soluble factors in the regulation of osteoclast activation and in the maintenance of bone density.2 OPG was identified as a new member of the tumour necrosis factor receptor superfamily; however, it lacked a hydrophobic transmembrane spanning sequence, indicating that it was a secreted receptor. As expression of this newly identified receptor led to an increase in bone density, blocked osteoclastogenesis and protected against ovariectomy associated bone loss, Simonet et al named it osteoprotegerin, from the …