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

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.This study was supported by projects (PI16/01282 and PI18/01584) integrated in the Plan Estatal de I+D+I 2016–2019 and cofounded by ISCIII-Subdirección General de Evaluación y Fomento de la Investigación del Fondo Europeo de Desarrollo Regional (FEDER). J.N.L.-C. and M.R.-M. were a recipient of a Sociedade Galega de Cardioloxía (SOGACAR) research grant. D.d.G.-C. was a recipient of a Juan de la Cierva-Incorporación grant from the Ministry of Science Innovation and Universities (IJCI-2016-29393). CIBER Cardiovascular (CB16/11/00403 to V.Ll.-C. and D.d.G.-C.) is a project from Carlos III Health Institute.Peer reviewe

Rol de sCD40L en la predicción de súper-respuesta a la terapia de resincronización cardiaca

Background. The aim of this paper is to analyze the role of the biomarkers Interleukin 6, Tumoral Necrosis Factor α, sCD40L, high sensitive Troponin T, high sensitive C-Reactive Protein and Galectin-3 in predicting super response (SR) to Cardiac Resynchronization Therapy (CRT), as they have not been studied in this field before. Methods. Clinical, electrocardiographic and echocardiographic data was obtained preimplant and after one year. SR was defined as reduction in LVESV ≥ 30% at one year follow-up. Blood samples were extracted preimplant. Multivariate logistic regression and ROC curves were performed. Results. 50 patients were included, 23 (46%) were SR. Characteristics related to SR were: female (35 vs. 11%, p=0.04), suffering from less ischemic cardiomyopathy (13 vs. 63%, p<0.0001) and lateral (0 vs. 18%, p=0.03), inferior (4 vs. 33%, p=0.01) and posterior infarction (0 vs. 22%, p=0.01); absence of mitral regurgitation (47% vs. 22%, p=0.04), wider QRS width (157.7±22.9 vs. 140.8±19.2ms, p=0.01), higher concentrations of sCD40L (6.9±5.1 vs. 4.4±3.3 ng/mL, p=0.02), and left ventricular lead more frequent in lateral medial position (69 vs. 26%, p=0.002). QRS width, lateral medial position of the lead and absence of mitral regurgitation were independent predictors of SR. sCD40L showed a moderate direct correlation with SR (r=0.39, p=0.02) and with the reduction of LVESV (r=0.44, p=0.02). Conclusion. sCD40L correlates significantly with SR to CRT. QRS width, absence of mitral regurgitation and lateral medial position of the lead are independent predictors of SR in this cohort.Fundamento. Analizar los biomarcadores Interleuquina 6, factor de necrosis tumoral α, sCD40L, troponina T hipersensible, proteína C-reactiva hipersensible y galectina-3 en la predicción de súper-respuesta (SR) a la terapia de resincronización cardiaca (TRC), ya que no han sido valorados con anterioridad. Material y métodos. Se recopilaron datos clínicos, electrocardiográficos y ecocardiográficos preimplante y al año. Se definió SR como disminución del VTSVI ≥ 30% al año de seguimiento. Las muestras sanguíneas fueron extraídas preimplante. Se realizó regresión logística multivariante y curvas ROC. Resultados. Se incluyeron 50 pacientes, 23 (46%) fueron SR.Las características relacionadas con la SR fueron: ser mujer (35 vs. 11%, p=0,04), sufrir menos cardiopatía isquémica (13 vs. 63%, p<0,0001) e infarto lateral (0 vs. 18%, p=0,03), inferior (4 vs. 33%, p=0,01) y posterior (0 vs. 22%, p=0,01); ausencia de insuficiencia mitral (47% vs. 22%, p=0,04), mayor anchura del QRS (157,7±22,9 vs. 140,8±19,2 ms, p=0,01), mayor concentración de sCD40L (6,9±5,1 vs. 4,4±3,3 ng/mL, p=0,02), y electrodo ventricular izquierdo más frecuentemente en posición lateral media (69 vs. 26%, p=0,002). El QRS, la posición lateral media del electrodo y la ausencia de insuficiencia mitral fueron predictores independientes de SR. sCD40L mostró una correlación moderada directa con SR (r=0,39, p=0,02) y con la disminución del VTSVI (r=0,44, p=0,02). Conclusiones. sCD40L se correlaciona significativamente con SR a la TRC. El QRS, la ausencia de insuficiencia mitral y la posición lateral media del electrodo son predictores independientes de SR en esta cohorte

Consort flow chart representing selection of patients included.

Consort flow chart representing selection of patients included.</p

Baseline clinical and echocardiographic characteristics of the study population.

Baseline clinical and echocardiographic characteristics of the study population.</p

Incidence of atrial fibrillation recurrence and lineal correlation in the 3 groups: Normal weight, overweight, obesity.

Incidence of atrial fibrillation recurrence and lineal correlation in the 3 groups: Normal weight, overweight, obesity.</p

Representation of odds ratio and 95% confidence interval of those variables included in the logistic regression.

Representation of odds ratio and 95% confidence interval of those variables included in the logistic regression.</p