Pathophysiological role of fatty acid‐binding protein 4 in Asian patients with heart failure and preserved ejection fraction

Abstract

Aims Systemic metabolic impairment is the key pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). Fatty acid-binding protein 4 (FABP4) is highly expressed in adipocytes and secreted in response to lipolytic signals. We hypothesized that circulating FABP4 levels would be elevated in patients with HFpEF, would correlate with cardiac structural and functional abnormalities, and could predict clinical outcomes. Methods and results Serum FABP4 measurements and echocardiography were performed in patients with HFpEF (n = 92) and those with coronary artery disease free of HF (n = 20). Patients were prospectively followed-up for a composite endpoint of all-cause mortality or HF hospitalization. Compared with patients with coronary artery disease, those with HFpEF had higher FABP4 levels [12.5 (9.1-21.0) vs. 43.5 (24.6-77.4) ng/mL, P < 0.0001]. FABP4 levels were associated with cardiac remodelling (left ventricular mass index: r = 0.29, P = 0.002; left atrial volume index: r = 0.40, P < 0.0001), left ventricular systolic and diastolic dysfunction (global longitudinal strain: r = À0.24, P = 0.01; E/e′ ratio: r = 0.29, P = 0.002; and N-terminal pro-B-type natriuretic peptide: r = 0.62, P < 0.0001), and right ventricular dysfunction (tricuspid annular plane systolic excursion: r = À0.43, P < 0.0001). During a median follow-up of 9.1 months, there were 28 primary endpoints in the HFpEF cohort. Event-free survival was significantly decreased in patients with FABP4 levels ≥43.5 ng/mL than in those with FABP4 levels <43.5 ng/mL (P = 0.003). Conclusions Serum FABP4 levels were increased in HFpEF and were associated with cardiac remodelling and dysfunction, and poor outcomes. Thus, FABP4 could be a potential biomarker in the complex pathophysiology of HFpEF.

Association of free fatty acid binding protein with central aortic stiffness, myocardial dysfunction and preserved ejection fraction heart failure

“…To our best knowledge, our study is the first to explore insights into the pathogenesis of HFpEF from increased central arterial stiffness related to higher adipocyte free fatty acid-binding protein level in a population manifesting cardiometabolic abnormality. Our present work further extended the findings and can be supplemental to prior study in that elevated a-FABP can play an independent role in central arterial stiffness in HFpEF development of ethnic Asians beyond the effect of myocardial suppression 19 . We further explored the prognostic utilization of HF using a-FABP when incorporated in a risk prediction model with central aortic indices measures.…”

“…As mentioned above, metabolic syndrome is closely associated with the development of arterial stiffness, HF, and cardiovascular deaths 2 , 3 . Interestingly, higher circulating levels of members of the fatty acid-binding protein (FABP) family have been shown to be tightly associated with aging and several metabolic phenotypes in the general population 18 , 19 . Higher cardiometabolic risks (i.e., obesity, arterial HTN, dyslipidemias, and DM) may all contribute to microvascular pathology or endothelial dysfunction, which is the central pathogenesis of HFpEF, through pro-inflammatory signaling 36 – 39 .…”

“…Furthermore, both clinical and experimental studies reported that a-FABP is widely involved in cardiovascular diseases, adverse cardiac remodeling and HF development 16 – 18 . As a-FABP has shown to modulate adverse cardiac metabolism in subjects manifesting CM disorders, higher a-FABP has been reported to contribute to HFpEF through suppressed myocardial function 16 – 19 . Nevertheless, it remains unknown that whether a-FABP may directly and adversely affect central arterial stiffness in subjects manifesting increased CM risk, a presumed key regulator in the pathogenesis of HFpEF 1 , 9 .…”

Features of Changes in the Structural and Functional State of the Myocardium in Patients with Acute Myocardial Infarction Depending on Body Mass Index Considering FABP4 and CTRP3 Levels

“…Von Jeinsen B et al [15] have determined a positive correlation between the content of FABP4 and cardiac troponin T and reported the low LVMMI, slightly reduced LVEDD and an inverse correlation between the LVMMI, LVEDD and FABP4 levels in patients with coronary heart disease. Harada T et al [5] have indicated increased LVMMI and determined a direct relationship between FABP4 and LVMMI levels, LA volume index, LV stiffness. In our study, FABP4 content was associated with an increase in myocardial mass and dilation of the heart cavities due to increased EDV, ESV, ESD, LVMMI1 and, thus, contributed to the deterioration of the structural and functional state of the myocardium in patients with AMI and obesity.…”

Right atrial pressure represents cumulative cardiac burden in heart failure with preserved ejection fraction

“…In this retrospective observational study, we evaluated the association between echocardiographic markers of RAP and clinical outcomes in stable patients with HFpEF. Some participant data from this study have been previously published, 16,18,21,22 but not as it relates to the prognostic value of eRAP. We identified patients who were admitted to either Gunma University Hospital in Maebashi, Japan, between January 2014 and June 2019 or Hokkaido University Hospital in Sapporo, Japan, between January 2014 and December 2018.…”