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Prognostic value of multiple emerging biomarkers in cardiovascular risk prediction in patients with stable cardiovascular disease

  • Namanjeet Ahluwalia
    Affiliations
    UMR U557 Inserm, U1125 Inra, Cnam, UFR SMBH, Université Paris 13, CRNH IdF, 74 rue Marcel Cachin, F-93017 Bobigny, France
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  • Jacques Blacher
    Affiliations
    UMR U557 Inserm, U1125 Inra, Cnam, UFR SMBH, Université Paris 13, CRNH IdF, 74 rue Marcel Cachin, F-93017 Bobigny, France

    Université Paris-Descartes, Faculté de Médecine, AP-HP, Hôtel-Dieu, Centre de Diagnostic et Thérapeutique, Paris, France
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  • Fabien Szabo de Edelenyi
    Correspondence
    Corresponding author. Tel.: +33 1 48 38 89 51; fax: +33 1 48 38 89 31.
    Affiliations
    UMR U557 Inserm, U1125 Inra, Cnam, UFR SMBH, Université Paris 13, CRNH IdF, 74 rue Marcel Cachin, F-93017 Bobigny, France
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  • Patrice Faure
    Affiliations
    Département de Biochimie, Toxicologie et Pharmacologie, UJF et CHU de Grenoble, Grenoble, France

    Laboratoire d'étude de la physiopathologie de l'hypoxie (HP2), Inserm U 1042, Grenoble, France
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  • Chantal Julia
    Affiliations
    UMR U557 Inserm, U1125 Inra, Cnam, UFR SMBH, Université Paris 13, CRNH IdF, 74 rue Marcel Cachin, F-93017 Bobigny, France

    Département de Santé Publique, Hôpital Avicenne, Bobigny, France
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  • Serge Hercberg
    Affiliations
    UMR U557 Inserm, U1125 Inra, Cnam, UFR SMBH, Université Paris 13, CRNH IdF, 74 rue Marcel Cachin, F-93017 Bobigny, France

    Département de Santé Publique, Hôpital Avicenne, Bobigny, France
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  • Pilar Galan
    Affiliations
    UMR U557 Inserm, U1125 Inra, Cnam, UFR SMBH, Université Paris 13, CRNH IdF, 74 rue Marcel Cachin, F-93017 Bobigny, France
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      Highlights

      • We found two natriuretic peptides with a significant prognostic value for CVD.
      • Homocysteine and CRP did not offer additional value for risk prediction.
      • NT-proBNP and MR-ANP, may offer additional tools for CVD risk stratification.

      Abstract

      Background

      Few studies have examined simultaneously the prognostic value of traditional and emerging biomarkers including atrial natriuretic peptide (ANP) and brain-type natriuretic peptide (BNP), for major cardiovascular disease (CVD) outcomes in patients with stable CVD, and results are equivocal.

      Design

      and Methods: Mid-regional pro-ANP (MR-proANP) and N-Terminal pro-BNP (NT-proBNP), CRP and homocysteine were measured in stable CVD patients (n = 1456; age: 61.8 y) at inclusion in the SU.FOL.OM3 cohort. Prospective association of biomarkers with risk of heart failure, major cardiovascular (non-fatal myocardial infarction, ischemic stroke or death from CVD) or overall cardiovascular event were examined with Cox proportional-hazards analyses. Increase in prediction risk upon addition of biomarker(s) to the traditional risk model was examined by change in C-statistic, NRI and IDI.

      Results

      During follow-up (median: 4.7 y), 40 heart failure, 145 major cardiovascular and 493 overall cardiovascular events were diagnosed. In models adjusted for age, sex, smoking, diabetes, serum creatinine and CVD inclusion criteria, NT-proBNP and CRP associated significantly with heart failure. Both natriuretic peptides predicted the risk of major cardiovascular events in adjusted models; Hazard ratio (HR) and 95% CI for each SD increase in MR-proANP and NT-proBNP were 1.24 (1.04–1.47), and 1.31 (1.09–1.57), respectively. The addition of NT-proBNP to a traditional risk model increased significantly the area-under-curve for heart failure and overall cardiovascular events (by 6 and 12%, respectively); addition of MR-proANP or homocysteine yielded modest (2%) but statistically significant increase for major cardiovascular events.

      Conclusion

      NT-proBNP consistently predicted CVD outcomes and may be useful singly or in combination with MR-proANP for risk-stratification in high-risk patients.

      Keywords

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