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Novel and conventional biomarkers for prediction of incident cardiovascular events in the community.

  • Olle Melander
  • Christopher Newton-Cheh
  • Peter Almgren
  • Bo Hedblad
  • Göran Berglund
  • Gunnar Engström
  • Margaretha Persson
  • Gustav Smith
  • Martin Magnusson
  • Anders Christensson
  • Joachim Struck
  • Nils G Morgenthaler
  • Andreas Bergmann
  • Michael J Pencina
  • Thomas J Wang
Publishing year: 2009
Language: English
Pages: 49-57
Publication/Series: JAMA: the journal of the American Medical Association
Volume: 302
Issue: 1
Document type: Journal article
Publisher: American Medical Association

Abstract english

CONTEXT: Prior studies have demonstrated conflicting results regarding how much information novel biomarkers add to cardiovascular risk assessment. OBJECTIVE: To evaluate the utility of contemporary biomarkers for predicting cardiovascular risk when added to conventional risk factors. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of 5067 participants (mean age, 58 years; 60% women) without cardiovascular disease from Malmö, Sweden, who attended a baseline examination between 1991 and 1994. Participants underwent measurement of C-reactive protein (CRP), cystatin C, lipoprotein-associated phospholipase 2, midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide, and N-terminal pro-B-type natriuretic peptide (N-BNP) and underwent follow-up until 2006 using the Swedish national hospital discharge and cause-of-death registers and the Stroke in Malmö register for first cardiovascular events (myocardial infarction, stroke, coronary death). MAIN OUTCOME MEASURES: Incident cardiovascular and coronary events. RESULTS: During median follow-up of 12.8 years, there were 418 cardiovascular and 230 coronary events. Models with conventional risk factors had C statistics of 0.758 (95% confidence interval [CI], 0.734 to 0.781) and 0.760 (0.730 to 0.789) for cardiovascular and coronary events, respectively. Biomarkers retained in backward-elimination models were CRP and N-BNP for cardiovascular events and MR-proADM and N-BNP for coronary events, which increased the C statistic by 0.007 (P = .04) and 0.009 (P = .08), respectively. The proportion of participants reclassified was modest (8% for cardiovascular risk, 5% for coronary risk). Net reclassification improvement was nonsignificant for cardiovascular events (0.0%; 95% CI, -4.3% to 4.3%) and coronary events (4.7%; 95% CI, -0.76% to 10.1%). Greater improvements were observed in analyses restricted to intermediate-risk individuals (cardiovascular events: 7.4%; 95% CI, 0.7% to 14.1%; P = .03; coronary events: 14.6%; 95% CI, 5.0% to 24.2%; P = .003). However, correct reclassification was almost entirely confined to down-classification of individuals without events rather than up-classification of those with events. CONCLUSIONS: Selected biomarkers may be used to predict future cardiovascular events, but the gains over conventional risk factors are minimal. Risk classification improved in intermediate-risk individuals, mainly through the identification of those unlikely to develop events.


  • Cardiac and Cardiovascular Systems
  • Cystatin C: blood
  • Cardiovascular Diseases: epidemiology
  • Cardiovascular Diseases: blood
  • C-Reactive Protein: metabolism
  • Biological Markers: blood
  • Adrenomedullin: blood
  • Atrial Natriuretic Factor: blood
  • Natriuretic Peptide
  • Brain: blood
  • Peptide Fragments: blood


  • Hypertension and Cardiovascular Disease
  • Diabetes and Endocrinology
  • Cardio-vascular Epidemiology
  • Internal Medicine
  • ISSN: 1538-3598
E-mail: gustav [dot] smith [at] med [dot] lu [dot] se

Associate professor


+46 46 17 26 33



Research project participant

Cardiovascular Epigenetics


Research project participant

Heart Failure and Mechanical Support


Project manager

Molecular Epidemiology and Cardiology

+46 46 17 26 33


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