Worldwide, atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults, associated with substantial morbidity and mortality [1]. Demographic factors (age, male sex, Caucasian ethnicity, lower socioeconomic status), health behaviours (smoking, alcohol, vigorous exercise, physical inactivity, competitive sports), cardiovascular health risk factors (hypertension, hyperlipidaemia, diabetes mellitus, chronic kidney disease, obesity, obstructive sleep apnoea), cardiovascular conditions (heart failure, coronary artery disease), disorders of heart rhythm (PR-prolongation, sick sinus syndrome, Wolff-Parkinson White syndrome), genetic factors (family history of AF, short QT syndrome), inflammation (C-reactive protein, fibrinogen, thyroid dysfunction, autoimmunity), and other factors (air pollution, sepsis) may cause incident AF [1].

Transition from paroxysmal to persistent/permanent AF is often characterized by advancing atrial structural remodelling [3] and associated with adverse cardiovascular events, hospitalizations, and death [1‒6]. Risk factors for AF progression include older age, heart failure, hypertension, chronic kidney disease, chronic pulmonary diseases, diabetes mellitus, previous stroke, and left atrial size, whereas the added predictive value of currently available biomarkers is not well defined [6].

Various biomarkers (troponin, natriuretic peptides, growth differentiation factor-15, von Willebrand factor) were associated with an improved performance of biomarker-based assessment of residual stroke risk among anticoagulated AF patients compared to clinical scores; although sometimes they are correlated with reflecting simply a sick heart or patient [7‒9]. The routine use of biomarker-based risk scores currently would not substantially add to initial stroke prevention treatment decisions in patients already qualifying for treatment based on the CHA2DS2-VASc score (and a limited practicality would be accompanied by increased healthcare costs) [10] but could better refine stroke risk differentiation between patients classified initially as low risk and those with a single non-sex CHA2DS2-VASc risk factor [11].

In their article, P. Wang and colleagues aimed to evaluate the expression of neuropeptide Y (NPY) in the circulating blood of AF patients, offering their insights for further exploration of the molecular mechanisms underlying AF development. Their results evidently showed the following: (1) patients with AF had a significantly higher NPY level; (2) independent risk factors for AF included age and NPY; (3) the level of NPY in patients with AF was positively correlated with BMI, left atrial diameter, and EHRA scores; (4) in peripheral blood, NPY was an independent factor for predicting AF, suggesting that it has potential clinical value as a biomarker to detect the pathogenesis and progression of AF. They concluded that the high expression of circulating NPY promotes the occurrence and development of AF and showed a NPY as a promising molecular biomarker for AF.

According to the literature data, the activation of the autonomic nervous system has been recognised as the central determinant of atrial arrhythmias [13]. NPY is a sympathetic neurotransmitter, the most abundant polypeptide in the heart, primarily in postganglionic sympathetic neurons and has been shown to have multiple effects on the cardiovascular system [13]. The mechanism by which NPY promotes AF may be that NPY increases peripheral vascular resistance, cardiac afterload, and myocardial oxygen consumption, causing increased myocardial ischaemia and thus exacerbating pathological changes in cardiac structures in patients with AF. NPY also acts on cardiomyocyte Y1 receptors to promote intracellular calcium transients and calcium sparks, inducing potential action changes [13]. Finally, NPY can promote cardiomyocyte fibrosis and contribute to arrhythmias by affecting cardiomyocyte action potentials.

In this study, the values of NPY and its mRNA increase with the severity of AF, i.e., patients with long-standing FA and severe EHRA scores (i.e., symptoms) have higher NPY values than subjects with paroxysmal FA. From this standpoint, when peripheral blood NPY increases, authors concluded we should be highly vigilant against the occurrence of AF and should improve the identification of AF complications. For patients with long-standing persistent AF, the high load of AF and increased sympathetic nerve activity may upregulate NPY expression. Therefore, it may further promote the formation of atrial fibrosis due to cardiac remodelling and cause the phenomenon of “atrial fibrillation induced atrial fibrillation (AF begets AF).” Timely blocking the occurrence of this process will prevent the irreversible development of AF and the transformation from paroxysmal AF to long-standing persistent AF. The best cut-off value of NPY for predicting AF between SR and AF group was 76.03 pg/mL, with a sensitivity of 82.22% and a specificity of 88.89% (shown in Fig. 1a). The best cut-off value for predicting long-standing persistent AF is 95.25 pg/mL, with a sensitivity of 83.33% and a specificity of 61.54% (shown in Fig. 1b) as both were shown by P. Wang and colleagues in their article.

Fig. 1.

a, b Predictive value of plasma NPY levels for AF. a In the AF and SR groups, the ROC curve of the predictive effect of peripheral blood NPY level on AF. b In paroxysmal AF and long-standing persistent AF, the ROC curve of the effect of peripheral blood NPY level on the prediction of long-standing persistent AF. AF, atrial fibrillation; AUC, area under the receiver operating characteristic curve; NPY, neuropeptide Y; ROC, receiver operating characteristic; SR, Sinus rhythm.

Fig. 1.

a, b Predictive value of plasma NPY levels for AF. a In the AF and SR groups, the ROC curve of the predictive effect of peripheral blood NPY level on AF. b In paroxysmal AF and long-standing persistent AF, the ROC curve of the effect of peripheral blood NPY level on the prediction of long-standing persistent AF. AF, atrial fibrillation; AUC, area under the receiver operating characteristic curve; NPY, neuropeptide Y; ROC, receiver operating characteristic; SR, Sinus rhythm.

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In conclusion, as a comprehensive marker of sympathetic nerve activity and inflammatory activity, NPY has obvious advantages in responding to AF activity compared with other biomarkers and changes in plasma NPY levels can predict the degree of progression of AF and thus the treatment success and overall outcomes.

The authors have no conflicts of interest to declare.

No external funding was received.

Marko Mornar Jelavic, Ovidiu Țica, Hrvoje Pintaric, and Otilia Țica drafted, reviewed, and revised the manuscript.

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