CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY
N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease
Tomas Jernberg, MD, PhD* ,*,
Bertil Lindahl, MD, PhD*,
Agneta Siegbahn, MD, PhD ,
Bertil Andren, MD, PhD ,
Gunnar Frostfeldt, MD, PhD*,
Bo Lagerqvist, MD, PhD*,
Mats Stridsberg, MD, PhD,
Per Venge, MD, PhD and
Lars Wallentin, MD, PhD*
* Department of Medical Sciences, Cardiology, Cardiothoracic Center, University Hospital, Uppsala, Sweden
Department of Medical Sciences, Clinical Chemistry, Cardiothoracic Center, University Hospital, Uppsala, Sweden
Department of Medical Sciences, Clinical Physiology, Cardiothoracic Center, University Hospital, Uppsala, Sweden
Uppsala Clinical Research Institute, University Hospital, Uppsala, Sweden
Manuscript received April 1, 2003;
revised manuscript received June 8, 2003,
accepted July 29, 2003.
* Reprint requests and correspondence: Dr. Tomas Jernberg, Department of Cardiology, Cardiothoracic Center, University Hospital, 751 85 Uppsala, Sweden.
tomas.jernberg{at}medsci.uu.se
OBJECTIVES: 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.
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Abbreviations and Acronyms
| | BNP | = brain natriuretic peptide | | cTnT | = cardiac troponin T | | FRISC | = FRagmin and fast revascularization during InStability in Coronary artery disease | | IL-6 | = interleukin-6 | | LVEF | = left ventricular ejection fraction | | MI | = myocardial infarction | | NT-proBNP | = N-terminal pro-brain natriuretic peptide | | OR | = odds ratio | | RR | = risk ratio | | UCAD | = unstable coronary artery disease |
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