Low Copeptin Levels Effectively Ruled Out MI

ORLANDO — Adding a new serum stress-marker test to the standard cardiac troponin assay allowed researchers to rule out acute MI with nearly 100% accuracy in 756 chest pain patients who presented to the emergency department.

The institution of an acute MI screening protocol that includes the new test for the stress marker copeptin plus the test for cardiac troponin—as well as ECG results and clinical findings—“may obviate the need for prolonged stay in the emergency department and troponin retesting after 6 hours in [about] two-thirds of patients,” a step that could have significant medical and economic benefits, Dr. Tobias Reichlin said at the annual meeting of the American College of Cardiology.

“A holy grail has been a simple blood test that works early on” to rule out or rule in an acute MI, noted Dr. Christopher P. Cannon, a cardiologist at Brigham and Women's Hospital in Boston. The test for copeptin looks “very promising” as part of an early screen, he added.

Copeptin is the C-terminal peptide that's removed from the vasopressin prohormone, and is a surrogate marker for endothelial stress, said Dr. Reichlin, a researcher in the department of biomedicine at the University of Basel (Switzerland). Copeptin is stable ex vivo for several days, and in healthy people exists in the blood at a median concentration of about 4 pmol/L.

The APACE (Advantageous Predictors of Acute Coronary Syndromes Evaluation) study examined the efficacy of using copeptin along with serum levels of cardiac troponin to rule out MI in chest pain patients who were seen in the emergency departments of several centers during April 2006-April 2008. A final adjudicated diagnosis made independently by two cardiologists identified 131 patients (17%) as definitely having an acute MI. About two-thirds of those patients had a non-ST elevation MI, and the rest had an ST elevation MI. The remaining 625 patients included 46% with noncardiac chest pain, 16% with unstable angina, 13% with noncoronary cardiac chest pain, and 9% with chest pain of unknown origin. Their average age was 62 years, and about two-thirds were men.

Copeptin levels were significantly higher among patients who were later confirmed to have ST elevation MIs, and were also significantly elevated in patients with non-ST elevation MIs, compared with patients who had any other type of chest pain.

During the first 4 hours after symptom onset, the copeptin level averaged 32 pmol/L among the MI patients. During the same period, cardiac troponin levels remained low, averaging about 4 mcg/L. More than 10 hours after symptom onset, the average copeptin level in the MI patients fell to about 10 pmol/L, whereas the average troponin level rose to about 30 mcg/L.

An analysis of the diagnostic accuracy of copeptin and troponin levels together by a receiver-operator curve showed that measuring those two analytes could account for 96% of the MI diagnoses.

Using a copeptin-level cut point of 14 pmol/L, combined with a standard troponin cut point, produced a sensitivity for diagnosing MI of 97.7% and a specificity of 76.3%, which resulted in a negative predictive value of 99.4% and a positive predictive value of 46.4% in the 756 patients studied, Dr. Reichlin said. If the analyte criteria had been applied to those patients, about two-thirds could have been quickly discharged from the emergency department with an MI ruled out.

Dr. Reichlin acknowledged that the number of patients studied was too small to allow a definitive conclusion.

The study was investigator initiated and received no commercial funding. Dr. Reichlin said he had no financial interests to report.

Copeptin testing “may obviate the need for prolonged stay in the emergency department.” DR. REICHLIN