A large-scale analysis has shown that a blood test previously found useful in diagnosing or ruling out heart failure in emergency room patients remains effective in patients with chronic kidney disease. The study also demonstrates that the test for a marker called NT-proBNP can identify patients at a higher risk for death, independent of kidney dysfunction. The report from investigators at the Massachusetts General Hospital (MGH) will appear in the January 3, 2006 Journal of the American College of Cardiology and is receiving early online release.
"It is well understood that kidney disease reduces the usefulness of testing for both NT-proBNP and a related biomarker called BNP, and the conventional understanding was that NT-proBNP was the more affected of the two," says James Januzzi Jr., MD, of the MGH Cardiology Division, the paper's senior author. "However, while kidney disease did lead to higher values of NT-proBNP in our study, what really matters is clinical performance; and at optimal cut-points, no matter how hard we looked, we found the relationship between chronic kidney disease and the diagnostic accuracy of NT-proBNP was no different than that of BNP. Our findings thus directly contradict observations based on smaller, less characterized patient populations."
Congestive heart failure, which occurs when an impaired heart muscle cannot pump blood efficiently, is a growing health problem and major cause of cardiac death. The diagnosis of heart failure may be challenging because its symptoms can overlap those of other conditions. Missing a heart failure diagnosis can put patients at high risk of serious problems, including death, but overdiagnosis may lead patients to receive unnecessary treatment.
Published earlier this year, the PRIDE study showed NT-proBNP to be highly sensitive and specific for the diagnosis of acute heart failure in patients with shortness of breath and to strongly predict patient deaths. A major concern about the widespread use of the marker had been previous assertions that kidney disease -- very common in patients with heart failure -- might confound the results of NT-proBNP testing, since levels of the marker were higher among those with reduced renal function.
Some researchers in the field argued that BNP was less affected by chronic kidney disease than was NT-proBNP. "We found no difference in our results when you examine them side-by-side with those for BNP," says Januzzi. "When you consider the data in totality, there just does not seem to be much difference between these two markers with respect to their diagnostic usefulness in patients with kidney disease. While kidney disease modestly reduces the diagnostic accuracy of both markers, when used in the appropriate manner, both tests appear to return identical information."
Besides the diagnostic value of NT-proBNP, the analysis evaluated the prospective value of NT-proBNP testing for predicting death within 60 days. "In fact, NT-proBNP measurement was an even stronger predictor of death in breathless patients with significant renal insufficiency, emphasizing the fact that the marker is likely detecting a true signal of cardiac disease in these patients," said Januzzi, an assistant professor of Medicine at Harvard Medical School. "This is a big step forward in the understanding of the optimal application of NT-proBNP measurement, as it removes one of the biggest obstacles that remained for the marker."
Co-authors of the study include first author Saif Anwaruddin, MD, now a fellow in cardiology at the Cleveland Clinic Foundation; Aaron Baggish, MD, Annabel Chen, MD, and Claudia Chae, MD, MPH, of MGH Cardiology; Donald M. Lloyd-Jones, MD, MsC, Northwestern University; Daniel Krauser, MD, New York Hospital; and Roderick Tung, MD, Cedars-Sinai Hospital, Los Angeles. The study was supported by a grant from Roche Diagnostics, which manufactures the NT-proBNP assay studied.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $500 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.
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