Nov. 12, 2002 DALLAS, Nov.12 – A rapid and inexpensive blood test that measures levels of a hormone predicted the long-term health of patients with heart attack and chest pain, according to a study published in today's rapid access issue of Circulation: Journal of the American Heart Association.
This hormone – B-type natriuretic peptide (BNP) – is elevated when the heart is damaged. A fragment of this hormone called the N-terminal fragment (N-BNP), can provide a clearer picture of a patient's likelihood of survival, more so than with current prognostic methods.
"In patients with acute coronary syndromes, N-BNP measurements taken early after admission identified patients at increased risk of early and late death," says senior author Kenneth Caidahl, M.D., Ph.D., a professor in the department of clinical physiology at the Sahlgrenska University Hospital in Göteborg, Sweden. "This relationship remained significant after adjusting for conventional risk markers. The most important finding was that N-BNP also predicted mortality among patients without clinical signs of left ventricular failure."
High levels of BNP are secreted by heart tissue when the heart is overloaded with pressure and its volume is expanded. By acting as a diuretic, the hormone helps return conditions to normal. In the last few years, testing in emergency departments for elevated levels of BNP has become a quick and accurate way to diagnose heart failure, allowing for earlier and better treatment. More recently, measuring the hormone has been shown to be a reliable way to predict future heart health in patients with heart attack or chest pain (angina). Newer studies show that N-BNP may provide prognostic information superior to BNP alone.
The prognosis of patients with heart attack or angina (also called acute coronary syndromes, or ACS) varies widely, and clinical, electrocardiographic and biochemical markers are used to identify high-risk patients who need aggressive intervention with a catheter procedure or surgery.
Caidahl and colleagues sought to clarify the role of N-BNP measurement in assessing ACS. They looked at 609 patients with ACS admitted to the coronary care unit of the Sahlgrenska University Hospital from September 1995 to February 2000. Death from all causes was the primary outcome measured, starting from the time of inclusion in the study to Sept. 15, 2001. Based on hospital records and personal interviews, the patients were classified as having or not having a medical history of heart attack, chest pain, congestive heart failure, diabetes and hypertension. Patients had N-BNP levels measured approximately three days after hospital admission, an echocardiographic study within five days of hospital admission, and left ventricular ejection fraction (LVEF) measured.
The study population consisted of 204 patients with ST-elevation heart attack, 220 with non-ST segment elevation heart attack, and 185 with unstable angina. After 51 months, with follow-up ranging from 19–72 months, 86 patients (14 percent) had died. Median N-BNP levels were significantly lower in long-term survivors than in patients dying (442 vs. 1306 pmol/L). In a statistical analysis, adjusting for patient age, heart failure status, and LVEF, N-BNP remained significantly associated with dying. Those in the highest group had twice the risk as those in the lowest group.
"N-BNP and BNP appear to be stronger predictors of short- and long-term mortality than conventional biochemical risk markers, including troponins, in acute coronary syndromes," says Caidahl. "This novel blood test is an important tool for risk stratification in acute coronary syndromes and may be measured routinely in this large and important patient group in the future. A method for rapid measurement of N-BNP has recently become commercially available."
In a related editorial, James A. de Lemos, M.D., of the University of Texas Southwestern Medical School in Dallas, and David A. Morrow, M.D., M.P.H., of Brigham and Women's Hospital in Boston, emphasize the importance of this study because it went further than similar studies by directly addressing limitations of previous analyses. They write that previous studies were "substudies within randomized controlled trials and may have enrolled highly selected patients…" and "…did not include routine measurement of LVEF." Conversely, the authors also caution that "clinical investigation of BNP in general, and in particular its application in ACS, is still in its infancy." They note that the optimal timing of measurement is not yet clear, threshold values would be useful, and direct comparisons of BNP and N-BNP are needed.
Even so, the editorial authors say that the study "answers several critical questions and contributes to a consistent emerging message: in patients with ACS, BNP adds important prognostic information to clinical and laboratory variables…." They add that the "magnitude of risk relationship associated with BNP appears to be greater than that associated with most currently available markers. Clearly BNP is telling us something that we did not previously know about factors associated with risk in patients with ACS."
Co-authors are Torbjørn Omland, M.D., Ph.D.; Anita Persson, M.Sc.; Leong Ng, M.D., Ph.D.; Russel O'Brien, M.D.; Thomas Karlsson, M.Sc.; Johan Herlitz, M.D., Ph.D.; and Marianne Hartford, M.D., Ph.D.
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