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CLINICAL RESEARCH: BIOMARKER

Heart-Type Fatty Acid-Binding Protein Predicts Long-Term Mortality After Acute Coronary Syndrome and Identifies High-Risk Patients Across the Range of Troponin Values

Niamh Kilcullen, MRCPI^_*,2,_*, Karthik Viswanathan, MRCP^_*,3, Rajiv Das, MRCP^_*,2, Christine Morrell^_*, Amanda Farrin, MSc, Julian H. Barth, MD, FRCP, FRCPath^,1, Alistair S. Hall, PhD, FRCP^_*,1 for the EMMACE-2 Investigators

^_* Coronary Artery Disease Clinical Research Network Group, Leeds Institute for Genetic, Health & Therapeutics, Leeds, United Kingdom
Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom
Department of Clinical Biochemistry, General Infirmary at Leeds, Leeds, United Kingdom.

Manuscript received November 6, 2006; revised manuscript received July 23, 2007, accepted August 21, 2007.

^_* Reprint requests and correspondence: Dr. Niamh Kilcullen, C-NET Group, Clinical Cardiology, G Floor Jubilee Building, General Infirmary at Leeds, Leeds, LS1 3EX Yorkshire, United Kingdom. (Email: niamhkilcullen{at}doctors.org.uk).

Objectives: Our aim was to determine if a high-performance assay for heart-type fatty acid-binding protein (H-FABP) has a role in predicting all-cause mortality after acute coronary syndrome (ACS).

Background: Heart-type fatty acid-binding protein is released into the circulation following myocardial ischemia and necrosis and therefore may be of value to physicians when caring for patients admitted to hospital with a clinical diagnosis of ACS.

Methods: This was a prospective observational study with a follow-up of 12 months. The H-FABP was measured 12 to 24 h after onset of symptoms in 1,448 patients admitted to hospital with ACS. The main outcome measure was all-cause mortality 1 year after index hospital admission. Multivariable analyses were conducted using the well validated GRACE (Global Registry of Acute Coronary Events) variables together with troponin I and highly sensitive C-reactive protein (hs-CRP).

Results: After 12 months of follow-up, 296 patients had died. Multivariable analysis demonstrated that H-FABP quartiles were strongly predictive of outcome: Q1 hazard ratio (HR) 1.0; Q2 HR 2.32 (95% confidence interval [CI] 1.25 to 4.30; p = 0.007); Q3 HR 3.17 (95% CI 1.73 to 5.82; p < 0.001); Q4 HR 4.88 (95% CI 2.67 to 8.93; p < 0.001). The crude all-cause 1-year mortality for unstable angina patients with H-FABP <5.8 µg/l was 2.1% compared with 22.9% for patients above this cutoff. The adjusted all-cause mortality HR in this group was 11.35 (95% CI 2.00 to 64.34; p = 0.006).

Conclusions: Heart-type fatty acid-binding protein predicts long-term mortality after ACS and identifies high-risk patients in a manner that is additive to the GRACE clinical risk factors, troponin, and hs-CRP, possibly as a result of identifying the occurrence of myocardial ischemia with or without necrosis.

Abbreviations and Acronyms   ACS = acute coronary syndrome   CV = coefficient of variation   ECG = electrocardiogram   H-FABP = heart-type fatty acid-binding protein   hs-CRP = highly sensitive C-reactive protein   MI = myocardial infarction   TnI = troponin I

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