en-Wen Wu, MD. PhD
Deputy Director of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan
Professor, National Yang-Ming University School of Medicine, Faulty of Medicine

Background: The fatty acid binding protein 3 (FABP3) is a cytoplasmic protein which was first isolated from ischemic rat hearts in 1988 and identified as being released from injured myocardium. Previous studies showed positive associations between FABP3 and acute coronary syndrome, acute heart failure (HF), post-cardiac surgery, high blood pressure and pulse pressure, acute kidney injury, acute pulmonary embolism, acute ischemic stroke, acute traumatic brain injury, severe sepsis, thyroid disorder. It has been proposed as a predictor of the perioperative cardiac risk and decline after transcatheter aortic valve replacement was noted. On the contrary, FABP4 is associated with the metabolic syndrome, diabetes mellitus, atherosclerosis, incident heart failure, and the prognosis of coronary artery disease (CAD). However, recent studies have not reported a significant correlation between FABP3 and FABP4 and cardiovascular (CV) mortality in high-risk patients or those with documented CAD after coronary intervention.
Method and Results: The Biosignature Study was a nationwide-multicenter prospective cohort study aimed to identify new biomarkers which could predict the prognosis in stable CAD patients. A detailed description of the methods and procedures has previously been described. The primary cardiovascular (CV) outcome was composite CV events, defined as cardiovascular or cerebrovascular death, myocardial infarction (MI), stroke, angina related-hospitalization, PAOD-related hospitalization and HF. Secondary outcomes included CV or cerebrovascular death, nonfatal MI, nonfatal stroke, and acute HF-related hospitalization.
The cut-off value of FABP3 of 4.143 pg/mL was determined using receiver operating characteristic curves. We found that the high FABP3 group had more than a two-fold higher rate of primary CV outcomes than the low FABP3 group (32.5% vs. 15.8%) and more than 40 times higher all-cause mortality rate of high FABP3 group than low FABP3 group (4.82% vs. 0.12%, both p<0.001) after 24 months of follow-up. The acute HF-related hospitalization rate was also significantly higher in the high FABP3 group (3.51% vs. 0.95%, p<0.005). The results remained significant after adjusting for baseline covariates. FABP3 was an independent predictor for CV outcomes in the patients with CAD, mainly in CV death and acute HF-related hospitalization.
On the other hand, Kaplan-Meier curves showed a significant association between FABP4 levels at baseline and composite CV outcomes during 24 month follow-up (log-rank test, p<0.003). The patients with the highest tertile of baseline FABP4 had an increased risk of composite CV outcomes (hazard ratio (HR) 1.662; 95% confidence interval (CI), 1.2–2.302; p=0.0022), which remained significant after multivariate adjustments for traditional risk factors and hs-CRP (HR 1.596; 95% CI, 1.088–2.342; p=0.0168). In contrast, FABP4 failed to show a significant association with cardiovascular/cerebrovascular death, nonfatal MI, or nonfatal stroke after multivariate adjustments (HR, 1.594; 95% CI, 0.651–3.904, p=0.3073). The study showed that elevated circulating levels of FABP4 were associated with an increased risk of composite CV events in the patients with CAD who received coronary interventions.
Because the exact mechanisms of FABP3 and FABP4 with CAD are not elucidated well, we further establish an in-vitro endothelial cell function assay system to evaluate their effects on the endothelial function, and dissect the complex relationships of biomarker-biomarker, and biomarker-environment interactions in patients with stable CAD. We expect that the translational platform from basic and clinical approaches on arterial endothelial function help understanding the relationships between FABPs on the endothelial function, and their potentials in high-risk population and stable CAD patients.