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CLINICAL RESEARCH: BIOMARKER

Thrombus Precursor Protein and Clinical Outcomes in Patients With Acute Coronary Syndromes

Jessica L. Mega, MD, MPH^_*,_*, David A. Morrow, MD, MPH, FACC^_*, James A. de Lemos, MD, FACC, Satishkumar Mohanavelu, MS^_*, Christopher P. Cannon, MD, FACC^_* and Marc S. Sabatine, MD, MPH, FACC^_*

^_* TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts
Division of Cardiology, Department of Medicine, University of Texas, Southwestern Medical Center, Dallas, Texas.

Manuscript received November 21, 2007; revised manuscript received January 8, 2008, accepted January 16, 2008.

^_* Reprint requests and correspondence: Dr. Jessica L. Mega, TIMI Study Group, Brigham and Women's Hospital, 350 Longwood Avenue, 1st Floor, Boston, Massachusetts 02115. (Email: jmega{at}partners.org).

Objectives: We sought to test the prognostic performance of thrombus precursor protein (TpP) in patients presenting with an acute coronary syndrome (ACS).

Background: Because thrombus formation is a critical step in the development of ACS, a measurement of activated coagulation could yield important information. Thrombus precursor protein is a biomarker that is used to measure soluble fibrin polymers, which are the penultimate products in fibrin formation.

Methods: We measured the levels of TpP in 284 healthy volunteers and in 2,349 patients with ACS.

Results: Median TpP concentrations were 3.6 µg/ml (interquartile range 2.6 to 5.5) in the volunteers and 8.9 µg/ml (interquartile range 4.9 to 15.9) in the ACS patients (p < 0.001). Patients with ACS who had elevated TpP were older, more likely to be women, and more likely to have diabetes and pre-existing CAD (p < 0.02 for each). Thrombus precursor protein levels greater than the median were associated with a significantly increased risk for the composite of death, myocardial infarction (MI), or recurrent ischemia leading to rehospitalization or urgent revascularization through 10 months (hazard ratio [HR] 1.45, p < 0.001), as well as death or MI (HR 1.42, p = 0.02). We found that TpP correlated only weakly with cardiac troponin I, B-type natriuretic peptide, and high-sensitivity C-reactive protein (|r| <0.15 for each). After adjusting for clinical characteristics, cardiac troponin I, high-sensitivity C-reactive protein, and B-type natriuretic peptide, we found that patients with TpP levels greater than the median remained at significantly increased risk for the composite outcome (adjusted HR 1.51, p = 0.001) and death or MI (adjusted HR 1.58, p = 0.02).

Conclusions: In patients with ACS, increased levels of TpP are associated with an increased risk of death or ischemic complications. The incorporation of a marker of activated coagulation, such as TpP, with established cardiovascular risk factors may offer valuable complementary insight into risk assessment in ACS.

Abbreviations and Acronyms   ACS = acute coronary syndrome(s)   BNP = B-type natriuretic peptide   CI = confidence interval   HR = hazard ratio   hsCRP = high-sensitivity C-reactive protein   NSTEMI = non–ST-segment elevation myocardial infarction   STEMI = ST-segment elevation myocardial infarction   TnI = cardiac troponin I   TpP = thrombus precursor protein   UA = unstable angina

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