SNOWMASS, COLO. — N-terminal pro–brain natriuretic peptide has a largely untapped potential for routine use in the office-based assessment of long-term risk in patients with chronic stable coronary artery disease.
Most physicians are familiar with NT-proBNP mainly as an in-hospital test for risk stratification and targeting therapy in the setting of acute coronary syndrome, but several years ago Danish investigators showed in a large longitudinal study that the cardiac biomarker is also an independent marker of mortality over the next dozen years in patients with stable CAD, Dr. Patrick T. O'Gara noted at a conference sponsored by the American College of Cardiology.
Indeed, NT-proBNP provided prognostic information above and beyond that imparted by the standard cardiovascular risk factors. For example, patients with a baseline NT-proBNP in excess of 455 pg/mL, placing them in the highest quartile, had an adjusted 2.4-fold greater risk of all-cause mortality during a median 9 years follow-up than those in the lowest quartile (a value less than 64 pg/mL).
A fourth-quartile NT-proBNP obtained in the physician's office was a stronger prognostic marker of all-cause mortality than diabetes, which conferred a 1.7-fold increased risk; cigarette smoking, with a 1.6-fold increase; or suspected heart failure, with a 1.8-fold elevated risk. Thus, the Danish findings broaden NT-proBNP's spectrum of clinical usefulness as a prognostic marker from the acute settings of the emergency department and coronary care unit to a population of intermediate-risk outpatients with stable chronic CAD, observed Dr. O'Gara of Brigham and Women's Hospital, Boston.
The study, conducted at the University of Copenhagen, involved 1,034 patients referred for coronary angiography because of signs or symptoms of CAD. During a maximum of 12 years and median of 9 years of follow-up, 288 patients died.
The mechanism underlying the association between NT-proBNP and long-term mortality risk in patients with stable CAD remains unclear. The association was independent of left ventricular ejection fraction and LV end-diastolic pressure, although it is possible that high levels of the biomarker reflect subtle LV remodeling detectable only by MRI or other high-definition imaging methods not employed in this study.
Another hypothesis advanced by the Danish investigators is that myocardial ischemia directly promotes NT-proBNP release (N. Engl. J. Med. 2005;352:666-75).
The Danish study was supported by the Danish Pharmacists Foundation. Dr. O'Gara indicated that he has no relevant financial interests.