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Diagnostic and prognostic value of NT-proBNP in stable systolic heart failure

Jens Rosenberg

English summary

The present PhD thesis is based on three manuscripts originating from the Department of Cardiology, Frederiksberg University Hospital

Background B‐type natriuretic peptides have been extensively investigated as diagnostic and prognostic markers of systolic heart failure, but primarily in hospital‐based settings. Our knowledge on the use of the N‐terminal part of the pro‐hormone, NT‐proBNP, in primary care is limited. Furthermore, the potential confounding effect of medical treatment – in particular β‐blockers ‐ on the diagnostic and prognostic performance of the B‐type natriuretic peptides has not been well studied. 

Aims The aims of the present PhD thesis were to describe 1) the impact of the use of NTproBNP in primary care on the referral pattern of general practitioners, 2) the prognostic value of NT‐proBNP in primary care with focus on threshold values, and finally 3) the influence of treatment with the β‐blocker, carvedilol, and the ACE inhibitor, enalapril, on the B‐type natriuretic peptides in patients with mild systolic heart failure. 

Methods and results After introduction of NT‐proBNP test in primary care to be used solely on the suspicion of heart failure, 4,877 patients were referred for an NT‐proBNP test at Copenhagen General Practitioners Laboratory between 2003 and 2005. In the 1,762 patients with elevated NT‐proBNP test results, only 23% were referred for an echocardiogram within 90 days. Not being referred was associated with a particularly poor prognosis. Based on all NT‐proBNP tests (N=5875) from primary care in the Copenhagen area in the period 2003 to 2005, an NT‐proBNP level of 83‐118 pg/ml was found to be associated with 90% increased risk of cardiovascular hospitalisation, when compared to the lowest decile (<34 pg/ml). Similarly, a peptide level of 229‐363 pg/ml was associated with 80% increased risk of death. Data from the Carvedilol ACE Inhibitor Remodelling Mild congestive heart failure EvaluatioN (CARMEN) trial in ambulatory heart failure patients showed no reduction in BNP and NTproBNP after six months treatment with carvedilol in contrast to patients treated with enalapril or the combination of carvedilol and enalapril. The prognostic value of BNP and NTproBNP was maintained after six months treatment with carvedilol. 

Conclusions ‐ It appears that patients in primary care could benefit from a more aggressive use of echocardiography in response to an elevated NT‐proBNP test result. The identified prognostic thresholds have the potential to be used to risk‐stratify waiting lists for echocardiography. Finally, NT‐proBNP and BNP can be used as risk markers of death and cardiovascular hospitalisations in systolic heart failure patients receiving carvedilol without ACE inhibition.