BIOMARKERS
Prognostic value of osteoprotegerin in heart failure after acute myocardial infarction
Thor Ueland, BSc*, ,*,
Rune Jemtland, PhD,
Kristin Godang, BSc,
John Kjekshus, MD, PhD ,
Aina Hognestad, MD*,||,
Torbjørn Omland, MD, PhD¶,
Iain B. Squire, MD**,
Lars Gullestad, MD, PhD||,
Jens Bollerslev, MD, PhD,
Kenneth Dickstein, MD, PhD# and
Pål Aukrust, MD, PhD*,
* Research Institute for Internal Medicine
Section of Endocrinology
Department of Cardiology
Section of Clinical Immunology and Infectious Diseases, National University Hospital, Oslo, Norway
|| Department of Cardiology, Baerum Hospital, Baeum, Norway
¶ Department of Medicine, Akershus University Hospital, Nordbyhagen, Norway
# University of Bergen, Cardiology Division, Central Hospital in Rogaland, Stavanger, Norway
** Department of Medicine and Therapeutics, University of Leicester, Leicester, United Kingdom
Manuscript received March 1, 2004;
revised manuscript received June 1, 2004,
accepted June 9, 2004.
* Reprint requests and correspondence: Dr. Thor Ueland, Section of Endocrinology, Medical Department National University Hospital, N-0027 Oslo, Norway (Email: thor.ueland{at}klinmed.uio.no).
OBJECTIVES: We sought to determine the relationship between osteoprotegerin (OPG) and clinical outcomes in patients with heart failure (HF) after acute myocardial infarction (AMI).
BACKGROUND: Arterial calcification is a prominent feature of arterial atherosclerosis and is associated with the occurrence of AMI. Osteoprotegerin is a recently discovered member of the tumor necrosis superfamily that may link the skeletal with the vascular system.
METHODS: We assayed plasma OPG levels in 234 patients with AMI complicated with HF and their relation to adverse outcomes during follow-up in patients randomly assigned to angiotensin-converting enzyme inhibition or angiotensin II antagonism. Blood was sampled at baseline (median three days after AMI), one month, and at one and two years.
RESULTS: Elevated plasma levels of OPG at baseline were associated with adverse outcomes during a median of 27 months follow-up; OPG remained an independent prognostic indicator also after adjustment for other known predictors of mortality and cardiovascular events after AMI (e.g., creatinine clearance, N-terminal B-type natriuretic peptide, high-sensitivity C-reactive protein). In non-survivors, plasma OPG levels were persistently elevated during longitudinal testing, suggesting that OPG may be of value for monitoring patients at risk.
CONCLUSIONS: Osteoprotegerin is a novel marker for cardiovascular mortality and clinical events in patients with AMI complicated with HF. These findings are compatible with the hypothesis suggesting a possible association between mediators of bone homeostasis and cardiovascular disease.
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Abbreviations and Acronyms
| | AMI = acute myocardial infarction | | HF = heart failure | | hsCRP = high-sensitivity C-reactive protein | | LVEF = left ventricular ejection fraction | | N-BNP = N-terminal B-type natriuretic peptide | | OPG = osteoprotegerin | | OPTIMAAL = Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan | RANKL = receptor activator of nuclear factor- B ligand | | TNF = tumor necrosis factor |
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