ProeA-Type Natriuretic Peptide, Proadrenomedullin, and N-Terminal ProeB-Type Natriuretic Peptide Used in a Multimarker Strategy in Primary Health Care in Risk Assessment of Patients With Symptoms of Heart Failure URBAN ALEHAGEN, MD, PhD, 1 ULF DAHLSTR € OM, MD, PhD, 1 JENS F. REHFELD, MD, DMSc, 2 AND JENS P. GOETZE, MD, DMSc 2 Link€ oping, Sweden; and Copenhagen, Denmark ABSTRACT Objective: Use of new biomarkers in the handling of heart failure patients has been advocated in the liter- ature, but most often in hospital-based populations. Therefore, we wanted to evaluate whether plasma mea- surement of N-terminal proeB-type natriuretic peptide (NT-proBNP), midregional proeA-type natriuretic peptide (MR-proANP), and midregional proadrenomedullin (MR-proADM), individually or combined, gives prognostic information regarding cardiovascular and all-cause mortality that could motivate use in el- derly patients presenting with symptoms suggestive of heart failure in primary health care. Methods and Results: The study included 470 elderly patients (mean age 73 years) with symptoms of heart failure in primary health care. All participants underwent clinical examination, 2-dimenstional echo- cardiography, and plasma measurement of the 3 propeptides and were followed for 13 years. All mortality was registered during the follow-up period. The 4th quartiles of the biomarkers were applied as cutoff values. NT-proBNP exhibited the strongest prognostic information with O4-fold increased risk for cardio- vascular mortality within 5 years. For all-cause mortality MR-proADM exhibited almost 2-fold and NT- proBNP 3-fold increased risk within 5 years. In the 5e13-year perspective, NT-proBNP and MR-proANP showed significant and independent cardiovascular prognostic information. NT-proBNP and MR-proADM showed significant prognostic information regarding all-cause mortality during the same time. In those with ejection fraction (EF) !40%, MR-proADM exhibited almost 5-fold increased risk of cardiovascular mortality with 5 years, whereas in those with EF O50% NT-proBNP exhibited O3-fold increased risk if analyzed as the only biomarker in the model. If instead the biomarkers were all below the cutoff value, the patients had a highly reduced mortality risk, which also could influence the handling of patients. Conclusions: The 3 biomarkers could be integrated in a multimarker strategy for use in primary health care. (J Cardiac Fail 2013;19:31e39) Key Words: Elderly, mulitmarker testing, heart failure, prognosis. The use of biomarkers to identify patients with heart fail- ure (HF) has gained considerable clinical interest. In addition to B-type natriuretic peptide (BNP) and the N-terminal frag- ment of its molecular precursor (NT-proBNP), several other markers may aid in risk assessment in elderly patients. BNP and NT-proBNP in plasma are now well established markers of myocardial strain 1 and provide important prognostic in- formation on the future risk of cardiovascular mortality. 2e5 Measurement of the structurally related A-type natriuretic peptide (ANP) has not been as pursued as much in recent clinical research. One of the contributing factors may be the relative instability of the bioactive peptide in vivo and From the 1 Division of Cardiovascular Medicine, Department of Medicine and Health Sciences, Faculty of Health Sciences, Link€ oping University, Department of Cardiology, University Hospital of Link€ oping, County Coun- cil of € Osterg€ otland, Link€ oping, Sweden and 2 Department of Clinical Bio- chemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Manuscript received August 29, 2012; revised manuscript received Oc- tober 29, 2012; revised manuscript accepted November 8, 2012. Reprint requests: Urban Alehagen, MD, PhD, Department of Cardiol- ogy, Heart Center, University of Link€ oping, SE-581 85 Link€ oping, Sweden. Tel: þ46-10-1030000; Fax: +46-10-1032224. E-mail: urban. alehagen@liu.se Funding: County Council of € Osterg€ otland, Swedish Heart and Lung Foundation, and University of Link€ oping. See page 38 for disclosure information. 1071-9164/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cardfail.2012.11.002 31 Journal of Cardiac Failure Vol. 19 No. 1 2013