The Prognostic
Value of B-Type Natriuretic
Peptide in Patients with Acute Coronary Syndromes
James A. de Lemos, M.D., David A. Morrow, M.D., M.P.H., Jane
H. Bentley, B.Sc., Torbjorn Omland, M.D., Ph.D., M.P.H., Marc S. Sabatine, M.D.,
Carolyn H. McCabe, B.S., Christian Hall, M.D., Ph.D., Christopher P. Cannon,
M.D., and Eugene Braunwald, M.D.
| Volume 345:1014-1021 |  |
October 4, 2001 | |
Number 14 |
|---|
ABSTRACTBackground Brain (B-type) natriuretic peptide is a neurohormone synthesized predominantly in ventricular myocardium. Although the circulating level of this neurohormone has been shown to provide independent prognostic information in patients with transmural myocardial infarction, few data are available forpatients with acute coronary syndromes in the absence of ST-segment elevation.
Methods We measured B-type natriuretic peptide in plasma specimensobtained a mean ( ±SD) of 40±20 hours after the onset of ischemic symptoms in 2525 patients from the Orbofiban in Patients with Unstable Coronary Syndromes–Thrombolysis in Myocardial Infarction 16 study.
Results The base-line level of B-type natriuretic peptide was correlated with the risk of death, heart failure, and myocardial infarction at 30 days and 10 months. The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of base-line B-type natriuretic peptide levels (P<0.001). This association remained significant in subgroups of patients who had myocardial infarction with ST-segment elevation (P=0.02), patients who had myocardial infarction without ST-segment elevation (P<0.001), and patients who had unstable angina (P<0.001). After adjustment for independent predictors of the long-term risk of death, the odds ratios for death at 10 months in the second, third, and fourth quartiles of B-type natriuretic peptide were 3.8 (95 percent confidence interval, 1.1 to 13.3), 4.0 (95 percent confidence interval, 1.2 to 13.7), and 5.8 (95 percent confidence interval, 1.7 to 19.7). The level of B-type natriuretic peptide was also associated with the risk of new or recurrent myocardial infarction (P=0.01) and new or worsening heart failure (P<0.001) at 10 months.
Conclusions A single measurement of B-type natriuretic peptide, obtained
in the first few days after the onset of ischemic symptoms, provides
predictive information for use in risk stratification across the
spectrum of acute coronary syndromes. Cardiac neurohormonal activation
may be a unifying feature among patients at high risk for death after
acute coronary syndromes.
Antoni Bayes-Genis, M.D., Cheryl A. Conover, Ph.D., Michael T. Overgaard, Ph.D., Kent R. Bailey, Ph.D., Michael Christiansen, M.D., David R. Holmes, Jr., M.D., Renu Virmani, M.D., Claus Oxvig, Ph.D., and Robert S. Schwartz, M.D.
| Volume 345:1022-1029 |
|
October 4, 2001 |
|
Number 14 |
|---|
ABSTRACT
Background Circulating markers
indicating the instability of atherosclerotic plaques could have
diagnostic value in unstable angina or acute myocardial infarction.
We evaluated pregnancy-associated plasma protein A (PAPP-A), a
potentially proatherosclerotic metalloproteinase, as a marker of
acute coronary syndromes.
Methods We examined the level of expression of PAPP-A in eight culprit unstable coronary plaques and four stable plaques from eight patients who had died suddenly of cardiac causes. We also measured circulating levels of PAPP-A, C-reactive protein, and insulin-like growth factor I (IGF-I) in 17 patients with acute myocardial infarction, 20 with unstable angina, 19 with stable angina, and 13 controls without atherosclerosis.
Results PAPP-A was abundantly expressed in plaque cells and extracellular matrix of ruptured and eroded unstable plaques, but not in stable plaques. Circulating PAPP-A levels were significantly higher in patients with unstable angina or acute myocardial infarction than in patients with stable angina and controls (P<0.001). A PAPP-A threshold value of 10 mIU per liter identified patients who had acute coronary syndromes with a sensitivity of 89.2 percent and a specificity of 81.3 percent. PAPP-A levels correlated with levels of C-reactive protein and free IGF-I, but not with markers of myocardial injury (troponin I and the MB isoform of creatine kinase).
Conclusions PAPP-A is present in unstable plaques, and circulatinglevels are elevated in acute coronary syndromes; these increased levels may reflect the instability of atherosclerotic plaques. PAPP-A is a new candidate marker of unstable angina and acute myocardial infarction.