European Heart Journal Advance Access originally published online on January 22, 2007
European Heart Journal 2007 28(11):1374-1381; doi:10.1093/eurheartj/ehl448
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N-terminal pro-brain natriuretic peptide, but not high sensitivity C-reactive protein, improves cardiovascular risk prediction in the general population
1 Research Center for Prevention and Health, Department of Clinical Physiology and Nuclear Medicine, Glostrup University Hospital, DK-2600 Glostrup, Denmark
2 Department of Cardiology, Rigshospitalet, Denmark
3 Department of Clinical Physiology and Nuclear Medicine, Glostrup University Hospital, Denmark
4 Department of Cardiology, Frederiksberg University Hospital, Denmark
5 Department of Internal Medicine, Glostrup University Hospital, Denmark
6 Department of Cardiology, Bispebjerg University Hospital, Denmark
Received 6 April 2006; revised 21 November 2006; accepted 30 November 2006; online publish-ahead-of-print 22 January 2007.
* Corresponding author. Tel: +45 4 323 2451; fax: +45 4 323 3928. E-mail address: mho{at}dadlnet.dk
Aim Serum N-terminal pro-brain natriuretic peptide (Nt-proBNP), high sensitivity (hs)-C-reactive protein, and urine albumin/creatinine ratio (UACR) are cardiovascular (CV) risk markers in the general population. The aim of this study was to determine whether they predicted CV events independently of established CV risk factors and whether they did so in an additive fashion.
Methods and results In a population-based sample of 2656 individuals, 41, 51, 61, and 71 years old, we measured UACR, serum Nt-proBNP, hs-C-reactive protein, insulin, lipids and plasma glucose, clinic blood pressures, body composition, left ventricular (LV) mass index, and ejection fraction (EF) by echocardiography and pulse wave velocity. During the following 9.4 years, the combined CV endpoint (CEP) of CV death (136), non-fatal stroke, or non-fatal myocardial infarction occurred in 219 subjects. After adjustment for established CV risk factors using Cox-regression analyses, CEP and CV death were predicted by log(Nt-proBNP)/SD [hazard ratio (HR) = 1.58 and HR = 1.80, both P < 0.001] and by log(UACR)/SD (HR = 1.44 and HR = 1.52, both P < 0.001) in an additive fashion, but not by log(hs-C-reactive protein)/SD (HR = 1.17, P = 0.06 and HR = 1.13, NS). CV risk functions were constructed on the basis of Cox-regression analyses. Inclusion of Nt-proBNP and UACR did not increase the area under the receiver-operating characteristic plots.
Conclusion Serum Nt-proBNP and UACR, but not hs-C-reactive protein, predicted CV events after adjustment for established CV risk factors including LV EF and relative wall thickness. However, more studies in relevant subgroups are needed before Nt-proBNP and UACR can be recommended for risk prediction in the general population to select subjects for primary prevention.
Key Words: N-terminal pro-brain natriuretic peptide • High sensitivity C-reactive protein • Albuminuria • Cardiovascular risk factors • Population survey • Left ventricular hypertrophy • Left ventricular systolic function • Pulse wave velocity • Prognosis
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