Sex-related differences of fatty acid-binding protein 4 and leptin levels in atrial fibrillation

Abstract

Aims Adiposity plays a key role in the pathogenesis of atrial fibrillation (AF). Our aim was to study the sex differences in adipokines levels according to AF burden. Methods and results Two independent cohorts of patients were studied: (i) consecutive patients with AF undergoing catheter ablation (n = 217) and (ii) a control group (n = 105). (i) Adipokines, oxidative stress, indirect autonomic markers, and leucocytes mRNA levels were analysed; (ii) correlation between biomarkers was explored with heatmaps and Kendall correlation coefficients; and (iii) logistic regression and random forest model were used to determine predictors of AF recurrence after ablation. Our results showed that: (i) fatty acid-binding protein 4 (FABP4) and leptin levels were higher in women than in men in both cohorts (P < 0.01). In women, FABP4 levels were higher on AF cohort (20 ± 14 control, 29 ± 18 paroxysmal AF and 31 ± 17 ng/mL persistent AF; P < 0.01). In men, leptin levels were lower on AF cohort (22 ± 15 control, 13 ± 16 paroxysmal AF and 13 ± 11 ng/mL persistent AF; P < 0.01). (ii) In female with paroxysmal AF, there was a lower acetylcholinesterase and higher carbonic anhydrase levels with respect to men (P < 0.05). (iii) Adipokines have an important role on discriminate AF recurrence after ablation. In persistent AF, FABP4 was the best predictor of recurrence after ablation (1.067, 95% confidence interval 1–1.14; P = 0.046). Conclusion The major finding of the present study is the sex-based differences of FABP4 and leptin levels according to AF burden. These adipokines are associated with oxidative stress, inflammatory and autonomic indirect markers, indicating that they may play a role in AF perpetuation.

The Role of Fatty Acid-Binding Protein 4 in the Characterization of Atrial Fibrillation and the Prediction of Outcomes after Catheter Ablation

“…Although the exact mechanisms remain elusive, clinical investigations have indicated sexual dimorphism in AF. Consistent with this rationale, in our previous study we have found an association between higher levels of FABP-4 in women with AF compared to men [ 8 ]. Recently, Ruben R. De With et al have shown that FABP4 levels were higher in women than in men with paroxysmal AF [ 22 ].…”

“…Leptin, an anorexic hormone released by adipocytes, regulates the pathogenesis of atrial fibrosis evoked by angiotensin II. Both adipokines are co-regulated during the inflammatory process of adipose tissue [ 7 ], and, interestingly, the plasma levels of both proteins differ between men and women depending on AF burden [ 8 ]. At present, conflicting evidence exists regarding the utility of biomarkers in detecting atrial cardiomyopathy as well as their role in predicting arrhythmia recurrence after AF ablation.…”

Different circulating biomarkers in women and men with paroxysmal atrial fibrillation: results from the AF-RISK and RACE V studies

“… 13 López-Canoa et al . 14 have shown an association between higher levels of FABP-4 in women with AF in comparison to men, as well as recurrence of AF after ablation in both sexes. In contrast to what we found, Magnussen et al .…”

Targeting Fatty Acid-Binding Protein 4 Improves Pathologic Features of Aortic Stenosis

“…The information on the sex-differences in FABP4 expression is limited to circulating FABP4 levels. Results from the clinical studies showed an increased FABP4 plasma level in the female gender in several pathological conditions such as coronary atherosclerosis [ 19 ] or atrial fibrillation [ 18 ]. Conversely, in patients with stable angina and chronic kidney disease, male sex was associated with higher plasma FABP4 levels [ 20 ].…”

“…Sex-differences in FABP4 expression is still a matter of debate. Women with atrial fibrillation [ 18 ] or coronary atherosclerosis [ 19 ] present higher plasma FABP4 levels, whereas women with stable angina and chronic kidney disease exhibit reduced plasma FABP4 [ 20 ].…”