Atherosclerosis 214 (2011) 203–208 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Pregnancy associated plasma protein-A as a marker for myocardial infarction and death in patients with stable coronary artery disease: A prognostic study within the CLARICOR Trial Kasper K. Iversen a,b,* , Børge Teisner c , Per Winkel b , Christian Gluud b , Erik Kjøller d , Hans Jørn Kolmos e , Per Rossen Hildebrandt f , Jørgen Hilden g , Jens Kastrup h , The CLARICOR Trial Group a Department of Cardiology, Hillerod Hospital, Hillerod, Denmark b Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark c Department of Immunology and Microbiology, University of Southern Denmark, Odense, Denmark d Department of Cardiology, Herlev Hospital, Copenhagen, Denmark e Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark f Department of Cardiology, Frederiksberg Hospital, Frederiksberg, Denmark g Department of Biostatistics, Institute of Public Health Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark h Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark article info Article history: Received 17 June 2010 Received in revised form 2 October 2010 Accepted 7 October 2010 Available online 3 November 2010 Keywords: Coronary artery disease Pregnancy associated plasma protein-A Mortality Biomarkers abstract Objective: Pregnancy associated plasma protein-A (PAPP-A) is a potential new marker for vulnerable plaques in the coronary arteries only examined in stable coronary disease (CAD) in patients undergoing coronary angiography. Here we address the prognostic value of serum PAPP-A in unselected stable CAD patients. Method: Blood samples were drawn at study entry. Serum PAPP-A values ≥4 mIU/L were considered ele- vated. Mortality and non-fatal myocardial infarction was prospectively registered. The primary outcome was the composite outcome of myocardial infarction and all-cause mortality, secondary outcomes were all-cause mortality and myocardial infarction. Results: Patients (n = 4243) were followed for a median of 2.8 years. In a Cox analysis, elevated PAPP-A was significantly related to the composite outcome of myocardial infarction and death (HR 1.99, 95% CI 1.62–2.45, p < 0.0005), all-cause mortality (HR 2.42, 1.92–3.06, p < 0.0005), and myocardial infarction (HR 1.40, 1.01–1.94, p = 0.046). After Holm’s correction, the latter significance disappeared. After adjustment for risk factors and medication at entry, elevated PAPP-A remained significantly related to the composite outcome (HR 1.51, 1.22–1.86, p < 0.0005) and all-cause mortality (HR 1.68, 1.32–2.13, p < 0.0005). Conclusion: In patients with stable CAD elevated serum PAPP-A seems promising as aid in identifying patients at high risk for death. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction In patients with stable coronary artery disease (CAD) both sta- ble and vulnerable plaques are often present. While a stable plaque evolves slowly and seldom results in acute coronary syndrome (ACS), unstable plaques may suddenly rupture and cause throm- bosis and subsequently result in myocardial infarction and death [1]. Biomarkers that could detect a vulnerable plaque could poten- Abbreviations: PAPP-A, pregnancy associated plasma protein-A; CAD, coronary artery disease; ACS, acute coronary syndrome. * Corresponding author at: Department of Cardiology, Hillerod Hospital, Helsevej 2, DK-3400 Hillerod, Denmark. Tel.: +45 48297345; fax: +45 48296015. E-mail address: kasper.iversen@dadlnet.dk (K.K. Iversen). tially be of great value in identifying patients at risk for an imminent coronary event. In 2001 pregnancy associated plasma protein-A (PAPP-A) was identified in vulnerable, but not in stable coronary plaques [2]. Since then several studies have demonstrated that PAPP-A is a poten- tially important biomarker in patients with ACS [3–10] and in the subgroup of patients with stable CAD undergoing elective coro- nary angiography [11–14]. Serum PAPP-A concentrations and the prognostic impact of PAPP-A in a large and unselected population of patients with documented stable CAD has not previously been described. The purpose of the present study was to assess the serum con- centrations of PAPP-A and the prognostic value of serum PAPP-A in relation to the combination of myocardial infarction and all-cause mortality, all-cause mortality, and myocardial infarction in patients 0021-9150/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2010.10.025