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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Circulating Osteoprotegerin Levels and Long-Term Prognosis in Patients With Acute Coronary Syndromes

Torbjørn Omland, MD, PhD, MPH^_*,, Thor Ueland, PhD^,1, Anna M. Jansson, MD, Anita Persson, MSc^||, Thomas Karlsson, MSc^¶, Camilla Smith, MD, Johan Herlitz, MD, PhD^¶, Pål Aukrust, MD, PhD^,1, Marianne Hartford, MD, PhD^¶,# and Kenneth Caidahl, MD, PhD^,||,_*

^_* Department of Medicine, Akershus University Hospital, Lørenskog, Norway
Faculty of Medicine, University of Oslo, Oslo, Norway
Research Institute for Internal Medicine, Rikshospitalet, Oslo, Norway
Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
^|| Department of Clinical Physiology, Sahlgrenska University Hospital, Göteborg, Sweden
^¶ Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden
^# AstraZeneca R&D, Mölndal, Sweden.

Manuscript received July 3, 2007; revised manuscript received September 17, 2007, accepted September 23, 2007.

^_* Reprint requests and correspondence: Dr. Kenneth Caidahl, Department of Clinical Physiology N2:01 & Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. (Email: kenneth.caidahl{at}ki.se).

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-B   RANKL = receptor activator of nuclear factor-B ligand