Elevated Circulating Adipocyte‐Fatty Acid Binding Protein Levels Predict Incident Cardiovascular Events in a Community‐Based Cohort: A 12‐Year Prospective Study

Abstract

BackgroundObesity is closely associated with various cardiovascular diseases (CVDs). Adipose tissue inflammation and perturbation of adipokine secretion may contribute to the pathogenesis of CVD. This study aimed to evaluate whether the 2 most abundant adipokines, adipocyte‐fatty acid binding protein (A‐FABP) and adiponectin, are independent risk factors predisposing to CVD.Method and ResultsWe investigated prospectively the 12‐year development of CVD in relation to the baseline levels of A‐FABP and adiponectin in a population‐based community cohort comprising 1847 Chinese subjects recruited from the Hong Kong Cardiovascular Risk Factors Prevalence Study 2 (CRISPS 2) cohort without previous CVD. Baseline serum levels of A‐FABP, adiponectin, and C‐reactive protein (CRP), an established biomarker predictive of CVD, were measured. In all, 182 (9.9%) of the 1847 Chinese subjects developed CVD during a median follow‐up of 9.4 years. The CVD group had more traditional risk factors, higher baseline levels of A‐FABP and CRP (both P<0.001), but similar adiponectin levels (P=0.881) compared with the non‐CVD group. In Cox regression analysis including both biomarkers, the adjusted HR for A‐FABP and CRP for subjects above the optimal cutoff values were 1.57 (95% CI, 1.14 to 2.16; P=0.006) and 1.60 (95% CI, 1.12 to 2.27; P=0.01), respectively, after adjustment for traditional risk factors. The category‐free net reclassification index, but not the c‐statistic, showed improvement in predictive performance by the addition of A‐FABP to the traditional risk factor model (P=0.017).ConclusionsCirculating A‐FABP level predicts the development of CVD after adjustment for traditional risk factors in a community‐based cohort. Its clinical use for CVD prediction warrants further validation.

Circulating Fatty Acid-Binding Protein 4 Concentration Predicts the Progression of Carotid Atherosclerosis in a General Population Without Medication

“…The serum FABP4 level has also been reported to predict long-term cardiovascular events. [16][17][18] Reduction of the FABP4 level would be a novel therapeutic strategy for preventing the development of atherosclerosis and reducing the incidence of atherosclerotic cardiovascular disease. However, it is unclear whether FABP4 acts by an intracellular signaling mechanism via unidentified receptors, though it is a potential adipokine, an adipocyte-derived bioactive molecule.…”

Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus

“…Furthermore, elevated serum concentration of FABP4 has been shown to be associated with obesity, insulin resistance, type 2 diabetes mellitus, hypertension, cardiac dysfunction, renal dysfunction, dyslipidemia, atherosclerosis, and cardiovascular events ( 8,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). However, little is known about the modulation of serum FABP4 level by therapeutic drugs including antidiabetic agents except for thiazolidinedione ( 25 ).…”

“…Serum FABP4 level has been reported to predict longterm cardiovascular events (22)(23)(24). Together with accumulating evidence indicating a signifi cant role of FABP4 in insulin resistance and atherosclerosis ( 4-6 ), the decrease in FABP4 level caused by DPP-4 inhibitors might have a preventive effect of cardiovascular events, though this issue has not yet been critically proved by randomized controlled trial studies using DPP-4 inhibitors.…”

Adiponectin gene variants and the risk of coronary heart disease: a 16-year longitudinal study

“…A total of 2012 subjects (915 men and 1097 women) who were without CHD at baseline had remained without CHD at subsequent follow-up visit(s). CHD events were defined based on ICD-9 (402, 404, 410-414, 425-429), which included, among others, acute myocardial infarction (MI), heart failure and angina pectoris as described in our previous study (13). Information on the dates of the CHD events and discharge diagnosis were obtained from the patients and also verified from the hospital authority database or the patients' private practitioners.…”