Hans Reiser1, Roland Klingenberg1, Danielle Hof1, Seraina Cooksley-Decasper1, Nina Fuchs1, Alexander Akhmedov1, Stefan Zoller1, Pedro Marques-Vidal1, Helena Marti Soler1, Dik Heg1, Ulf Landmesser1, Nicolas Rodondi1, Francois Mach1, Stephan Windecker1, Peter Vollenweider1, Christian M Matter1, Thomas F Lüscher1, Arnold von Eckardstein2, Joanna Gawinecka1. 1. From the Institute of Clinical Chemistry (H.R., D.H., S.C.-D., A.v.E., J.G.), Department of Cardiology, University Heart Center (R.K., N.F., A.A., U.L., C.M.M.), University Hospital Zurich, Zurich, Switzerland; Competence Center for Systems Physiology and Metabolic Diseases (CC-SPMD), Zurich, Switzerland (H.R., A.v.E.); Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland (S.C.-D., U.L., C.M.M., T.F.L., A.v.E.); Bioinformatics, Genetic Diversity Center, Federal Institute of Technology (ETH), Zurich, Switzerland (S.Z.); Department of Internal Medicine (P.M.-V., P.V.), Institute of Social and Preventive Medicine, Department of Community Medicine and Public Health (H.M.S.), University of Lausanne, Lausanne, Switzerland; Institute of Social and Preventive Medicine, and Clinical Trials Unit, Department of Clinical Research (D.H.), Department of General Internal Medicine (N.R.), Department of Cardiology, Swiss Cardiovascular Center Bern (S.W.), University Hospital Bern, Bern, Switzerland; and Department of Cardiology, University Hospital Geneva, Geneva, Switzerland (F.M.). 2. From the Institute of Clinical Chemistry (H.R., D.H., S.C.-D., A.v.E., J.G.), Department of Cardiology, University Heart Center (R.K., N.F., A.A., U.L., C.M.M.), University Hospital Zurich, Zurich, Switzerland; Competence Center for Systems Physiology and Metabolic Diseases (CC-SPMD), Zurich, Switzerland (H.R., A.v.E.); Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland (S.C.-D., U.L., C.M.M., T.F.L., A.v.E.); Bioinformatics, Genetic Diversity Center, Federal Institute of Technology (ETH), Zurich, Switzerland (S.Z.); Department of Internal Medicine (P.M.-V., P.V.), Institute of Social and Preventive Medicine, Department of Community Medicine and Public Health (H.M.S.), University of Lausanne, Lausanne, Switzerland; Institute of Social and Preventive Medicine, and Clinical Trials Unit, Department of Clinical Research (D.H.), Department of General Internal Medicine (N.R.), Department of Cardiology, Swiss Cardiovascular Center Bern (S.W.), University Hospital Bern, Bern, Switzerland; and Department of Cardiology, University Hospital Geneva, Geneva, Switzerland (F.M.). arnold.voneckardstein@usz.ch.
Abstract
OBJECTIVE: Blood-borne biomarkers reflecting atherosclerotic plaque burden have great potential to improve clinical management of atherosclerotic coronary artery disease and acute coronary syndrome (ACS). APPROACH AND RESULTS: Using data integration from gene expression profiling of coronary thrombi versus peripheral blood mononuclear cells and proteomic analysis of atherosclerotic plaque-derived secretomes versus healthy tissue secretomes, we identified fatty acid-binding protein 4 (FABP4) as a biomarker candidate for coronary artery disease. Its diagnostic and prognostic performance was validated in 3 different clinical settings: (1) in a cross-sectional cohort of patients with stable coronary artery disease, ACS, and healthy individuals (n=820), (2) in a nested case-control cohort of patients with ACS with 30-day follow-up (n=200), and (3) in a population-based nested case-control cohort of asymptomatic individuals with 5-year follow-up (n=414). Circulating FABP4 was marginally higher in patients with ST-segment-elevation myocardial infarction (24.9 ng/mL) compared with controls (23.4 ng/mL; P=0.01). However, elevated FABP4 was associated with adverse secondary cerebrovascular or cardiovascular events during 30-day follow-up after index ACS, independent of age, sex, renal function, and body mass index (odds ratio, 1.7; 95% confidence interval, 1.1-2.5; P=0.02). Circulating FABP4 predicted adverse events with similar prognostic performance as the GRACE in-hospital risk score or N-terminal pro-brain natriuretic peptide. Finally, no significant difference between baseline FABP4 was found in asymptomatic individuals with or without coronary events during 5-year follow-up. CONCLUSIONS: Circulating FABP4 may prove useful as a prognostic biomarker in risk stratification of patients with ACS.
OBJECTIVE: Blood-borne biomarkers reflecting atherosclerotic plaque burden have great potential to improve clinical management of atherosclerotic coronary artery disease and acute coronary syndrome (ACS). APPROACH AND RESULTS: Using data integration from gene expression profiling of coronary thrombi versus peripheral blood mononuclear cells and proteomic analysis of atherosclerotic plaque-derived secretomes versus healthy tissue secretomes, we identified fatty acid-binding protein 4 (FABP4) as a biomarker candidate for coronary artery disease. Its diagnostic and prognostic performance was validated in 3 different clinical settings: (1) in a cross-sectional cohort of patients with stable coronary artery disease, ACS, and healthy individuals (n=820), (2) in a nested case-control cohort of patients with ACS with 30-day follow-up (n=200), and (3) in a population-based nested case-control cohort of asymptomatic individuals with 5-year follow-up (n=414). Circulating FABP4 was marginally higher in patients with ST-segment-elevation myocardial infarction (24.9 ng/mL) compared with controls (23.4 ng/mL; P=0.01). However, elevated FABP4 was associated with adverse secondary cerebrovascular or cardiovascular events during 30-day follow-up after index ACS, independent of age, sex, renal function, and body mass index (odds ratio, 1.7; 95% confidence interval, 1.1-2.5; P=0.02). Circulating FABP4 predicted adverse events with similar prognostic performance as the GRACE in-hospital risk score or N-terminal pro-brain natriuretic peptide. Finally, no significant difference between baseline FABP4 was found in asymptomatic individuals with or without coronary events during 5-year follow-up. CONCLUSIONS: Circulating FABP4 may prove useful as a prognostic biomarker in risk stratification of patients with ACS.
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