Although fatty acid binding protein 4 (FABP4) may increase risk of diabetes and exert negative cardiac inotropy, it is unknown whether plasma concentrations of FABP4 are associated with incidence of sudden cardiac death (SCD). We prospectively analyzed data on 4,560 participants of the Cardiovascular Health Study. FABP4 was measured at baseline using ELISA, and SCD events were adjudicated through review of medical records. We used Cox proportional hazards to estimate effect measures. During a median followup of 11.8 years, 146 SCD cases occurred. In a multivariable model adjusting for demographic, lifestyle, and metabolic factors, relative risk of SCD associated with each higher standard deviation (SD) of plasma FABP4 was 1.15 (95% CI: 0.95–1.38), . In a secondary analysis stratified by prevalent diabetes status, FABP4 was associated with higher risk of SCD in nondiabetic participants, (RR per SD higher FABP4: 1.33 (95% CI: 1.07–1.65), ) but not in diabetic participants (RR per SD higher FABP4: 0.88 (95% CI: 0.62–1.27), ), for diabetes-FABP4 interaction 0.049. In summary, a single measure of plasma FABP4 obtained later in life was not associated with the risk of SCD in older adults overall. Confirmation of our post-hoc results in nondiabetic people in other studies is warranted. 1. Introduction Each year, nearly half a million sudden cardiac deaths (SCDs) occur in the US [1, 2]. Although more than 80% of SCDs occur in patients with coronary heart disease or congestive heart failure, conditions strongly linked to adiposity [3–5], several traditional adiposity-related risk factors such as high cholesterol or high blood pressure are not strongly predictive of SCD. Adiposity [6] and metabolic syndrome [7] have been positively associated with an increased QT dispersion, another risk factor for SCD [8–10]. Furthermore, weight loss may lead to a decrease in QT dispersion [11], suggesting that adiposity may influence the risk of SCD. Adipose tissues produce various adipokines including fatty acid binding protein 4 (FABP4)—also referred to as aP2 or a FABP, a carrier protein that transports fatty acids and other lipophilic substances between extra- and intracellular membranes [12–14] and exerts diverse effects on modulation of inflammation, thrombogenicity, insulin resistance, and other metabolic pathways [15–18]. In isolated rat cardiomyocytes, FABP4 acutely depressed shortening amplitude and intracellular systolic peak Ca(2+) in a dose-response fashion [19]. This suggests that FABP4 may play an important role in cardiac depolarization and possibly cardiac
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