Clinical Research
Coronary Artery Disease
Circulating Osteoprotegerin Levels and Long-Term Prognosis in Patients With Acute Coronary Syndromes

https://doi.org/10.1016/j.jacc.2007.09.058Get rights and content
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Objectives

This study was designed to assess the association between osteoprotegerin (OPG) levels on admission and long-term prognosis in patients with acute coronary syndromes (ACS).

Background

Osteoprotegerin, a member of the tumor necrosis factor receptor superfamily, has pleiotropic effects on bone metabolism, endocrine function, and the immune system.

Methods

Serum samples for OPG analysis were obtained within 24 h of admission in 897 ACS patients (median age 66 years, 71% men) and related to the incidence of death, heart failure (HF) hospitalizations, myocardial infarction (MI), and stroke.

Results

A total of 261 patients died during a median follow-up of 89 months. The baseline OPG concentration was strongly associated with increased long-term mortality (hazard ratio [HR] for HR per 1 SD increase in logarithmically transformed OPG level 1.7 [range 1.5 to 1.9] p < 0.0001) and HF hospitalizations (HR 2.0 [range 1.6 to 2.5]; p < 0.0001) but weaker with recurrent MI (HR 1.3 [range 1.0 to 1.5]; p = 0.02) and not with stroke (HR 1.2 [range 0.9 to 1.6]; p = 0.35). After adjustment for conventional risk markers, including troponin I, C-reactive protein (CRP), B-type natriuretic peptide (BNP), and ejection fraction, the association remained significant for mortality (HR 1.4 [range 1.2 to 1.7]; p < 0.0001) and HF hospitalization (HR 1.6 [range 1.2 to 2.1]; p = 0.0002), but not recurrent MI. By comparison of the area under the receiver-operating characteristics curves, OPG performed similarly to BNP and ejection fraction and significantly better than CRP and troponin I as a predictor of death.

Conclusions

Serum OPG is strongly predictive of long-term mortality and HF development in patients with ACS, independent of conventional risk markers.

Abbreviations and Acronyms

ACS
acute coronary syndromes
BNP
B-type natriuretic peptide
CI
confidence interval
CRP
C-reactive protein
HF
heart failure
HR
hazard ratio
LVEF
left ventricular ejection fraction
MI
myocardial infarction
OPG
osteoprotegerin
RANK
receptor activator of nuclear factor-κB
RANKL
receptor activator of nuclear factor-κB ligand

Cited by (0)

This study was supported by the Swedish Research Council (14231), the Swedish Heart and Lung Foundation, the Västra Götaland Region, the Vardal Foundation, Göteborg University, and the Göteborg Medical Society.

1

Drs. Aukrust and Ueland are listed as co-inventors on a pending patent application on the use of osteoprotegerin as a prognostic marker in cardiovascular disorders.