title: Pro-A-type natriuretic peptide, proadrenomedullin, and N-terminal pro-B-type natriuretic peptide used in a multimarker strategy in primary health care in risk assessment of patients with symptoms of heart failure.
abstract: OBJECTIVE
  Use of new biomarkers in the handling of heart failure patients has been advocated in the literature, but most often in hospital-based populations. Therefore, we wanted to evaluate whether plasma measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional pro-A-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 elderly patients presenting with symptoms suggestive of heart failure in primary health care.
  
  
  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 echocardiography, 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 >4-fold increased risk for cardiovascular 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 5-13-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 >50% NT-proBNP exhibited >3-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.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University, Department of Cardiology, University Hospital of Linköping, County Council of Östergötland, Linköping, Sweden. urban.alehagen@liu.se
authors.forename: Urban
authors.initials: U
authors.lastname: Alehagen
authors.forename: Ulf
authors.initials: U
authors.lastname: Dahlström
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.forename: Jens P
authors.initials: JP
authors.lastname: Goetze
mesh_terms: D053607:Adrenomedullin / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D016011:Normal Distribution; D010446:Peptide Fragments / Q000097:blood*; D011320:Primary Health Care; D016016:Proportional Hazards Models; D011498:Protein Precursors / Q000097:blood*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013548:Sweden; D013997:Time Factors
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011498:Protein Precursors; C109794:pro-brain natriuretic peptide (1-76); C088633:proadrenomedullin; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin