Circulating FABP4 Is a Prognostic Biomarker in Patients With Acute Coronary Syndrome but Not in Asymptomatic Individuals

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.

Plasma Levels of Fatty Acid–Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality Among Men With Type 2 Diabetes

“…12,13 Another study found that circulating FABP4 predicted the risk of adverse cerebrovascular or cardiovascular events in patients with acute coronary syndrome but not in asymptomatic individuals. 27 The underlying mechanisms linking FABP4 with cardiometabolic conditions are illustrated in animal studies. In obese mice, the use of a small molecular inhibitor of FABP4 or targeted deletion of FABP4 could protect against the development of insulin resistance and lipid dysregulation.…”

Role of the fatty acid-binding protein 4 in heart failure and cardiovascular disease

“…In humans, FABP4 has been related to subclinical coronary atherosclerosis in type 2 diabetes mellitus subjects (Bagheri et al 2010), and circulating FABP4 levels are also associated with increased carotid intima-media thickness, ischaemic stroke, coronary atherosclerotic burden and the number of stenotic coronary arteries , Rhee et al 2009, Miyoshi et al 2010, Bao et al 2011, Doi et al 2011, Holm et al 2011, Tso et al 2011, Huang et al 2013. Recently, FABP4 has been proposed as a prognostic biomarker in patients with acute coronary syndrome (Reiser et al 2015). In addition, FABP4 is an important predictor of cardiovascular outcomes in patients with either coronary heart disease or acute ischaemic stroke (Holm et al 2011, von Eynatten et al 2012.…”

Association of A‐FABP gene polymorphism and mRNA expression with intramuscular fat content (IMF) in Baicheng‐You chicken

“…Functions of the fatty acid-binding protein (FABP) gene family have been connected with the uptake, transportation and metabolism of intracellular free fatty acids (Migdał et al, 2018). Polymorphisms of the A-FABP gene are found to be prognostic biomarkers in patients with acute coronary syndrome (Reiser et al, 2015) and type 2 diabetes mellitus (Alqahtani et al, 2016). They are usually researched as candidate genes that affect the deposition of intramuscular fat in pigs (Zhang et al, 2013), cattle (Jurie et al, 2007), chickens (Zhou et al, 2018), ducks (Saez et al, 2009), goats (Wang, Geng, Ji, & Chang, 2012) and sheep (Wang et al, 2014).…”