N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease.
OBJECTIVE
We sought to examine whether measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), in addition to cardiac troponin T (cTnT) and interleukin-6 (IL-6), improve the ability to identify high-risk patients who benefit from an early invasive strategy.


BACKGROUND
Biochemical indicators of cardiac performance (e.g., NT-proBNP), inflammation (e.g., IL-6), and myocardial damage (e.g., cTnT) predict mortality in unstable coronary artery disease (UCAD) (i.e., unstable angina or non-ST-segment elevation myocardial infarction [MI]). In these patients, an early invasive treatment strategy improves the outcome.


METHODS
Levels of NT-proBNP, cTnT, and IL-6 were measured in 2,019 patients with UCAD randomized to an invasive or non-invasive strategy in the FRagmin and fast revascularization during InStability in Coronary artery disease (FRISC-II) trial. Patients were followed up for two years to determine death and MI.


RESULTS
Patients in the third NT-proBNP tertile had a 4.1-fold (95% confidence interval [CI] 2.4 to 7.2) and 3.5-fold (95% CI 1.8 to 6.8) increased mortality in the non-invasive and invasive groups, respectively. An increased NT-proBNP level was independently associated with mortality. In patients with increased levels of both NT-proBNP and IL-6, an early invasive strategy reduced mortality by 7.3% (risk ratio 0.46, 95% CI 0.21 to 1.00). In patients with lower NT-proBNP or IL-6 levels, the mortality was not reduced. Only elevated cTnT was independently associated with future MI and a reduction of MI by means of an invasive strategy.


CONCLUSIONS
N-terminal proBNP is independently associated with mortality. The combination of NT-proBNP and IL-6 seems to be a useful tool in the identification of patients with a definite survival benefit from an early invasive strategy. Only cTnT is independently associated with future MI and a reduction of MI by an invasive strategy.
Jernberg
Tomas
T
Department of Medical Sciences, Cardiology, Cardiothoracic Center, University Hospital, Uppsala, Sweden. tomas.jernberg@medsci.uu.se
Lindahl
Bertil
B
Siegbahn
Agneta
A
Andren
Bertil
B
Frostfeldt
Gunnar
G
Lagerqvist
Bo
B
Stridsberg
Mats
M
Venge
Per
P
Wallentin
Lars
L
D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood* / Q000401:mortality / Q000473:pathology; D004453:Echoencephalography; D006801:Humans; D007249:Inflammation / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D020097:Natriuretic Peptide, Brain; D009336:Necrosis; D009419:Nerve Tissue Proteins / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D020107:Troponin T / Q000097:blood
D015415:Biomarkers; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain