ELS BIOMARCADORS SANGUINIS COM A EINES PER A LA PREVENCIÓ DEL ICTUS ASSOCIAT A LA FIBRIL·LACIÓ AURICULAR

Abstract

Stroke is one of the main causes of death and disability worldwide. Atrial fibrillation (AF) is a common cardiac arrhythmia with a prevalence of 1-4% in the general population. It increases the risk of ischemic stroke by 5 and may also be one of the underlying causes of many cryptogenic strokes/ESUS. In the presence of this arrhythmia, anticoagulant therapy may reduce the risk of stroke. However, AF is often asymptomatic and paroxysmal, difficulting its detection. In addition, AF has also been postulated as a cause of silent brain infarts (SBI), even in AF considered of low embolic risk according to the CHADS2 and CHA2DS2VASc clinical scores. Detection of SBI could be considered an initial manifestation of cerebrovascular disease, requiring the implementation of prevention strategies in these patients. Blood biomarkers could be useful tools in the diagnosis and management of AF thanks to their “biological memory”. In addition, biomarkers can give us information about the pathophysiology of AF and its relationship to cerebrovascular pathology. Although multiple candidate molecules have been proposed in this context, none of them are currently used in clinical practice. This Doctoral Thesis aims to identify blood biomarkers of AF and describe its application in contexts of primary and secondary stroke prevention. For this purpose, we used blood samples from patients included in three cohorts representing different clinical indications, such as the diagnosis of AF in asymptomatic populations and cryptogenic strokes, or the detection of SBI in patients with AF. Therefore, the studies of this thesis have evaluated the use of biomarkers already described in the literature in these clinical indications. As a result, we have shown that the biomarkers studied were not able to detect cases of paroxysmal AF alone in asymptomatic patients, reducing their potential as population-based screening tools. However, its combination with rapid AF detection devices such as MyDiagnostick or WatchBP should be explored. In contrast, in secondary prevention, both BNP and NT-proBNP were predictors of AF detected during the first month after a cryptogenic stroke, with BNP showing slightly better results. In both cases, in terms of the detection of AF, natriuretic peptides were the candidates showing the best results. Its combination with biomarkers from other pathways such as Ang-2, marker of endothelial damage, could increase its diagnostic capacity. On the other hand, Ang-2 along with BMP-10 and FGF-23 showed higher levels in patients with low-risk AF and SBI in comparison to patients without SBI. Finally, we conducted discovery biomarker studies using a proteomic platform based on the technology of DNA aptamers in order to identify new biomarkers that could complement those already described. These studies have allowed us to identify and explore proteins and pathways that could be relevant in the pathophysiology of AF. Of these, DPP7 should be further explored as a possible biomarker of stroke etiology. In addition, we have proposed a new approach to discover new biomarkers and pathways in this context, taking into account the concept of atrial cardiomyopathy and using echocardiographic parameters. Overall, the results of this thesis contribute to an applied view of the use of blood biomarkers in the management of AF. In the future, some of these markers could be implemented in clinical practice in order to improve stroke prevention strategies

Date of Award	1 Apr 2022
Original language	Catalan
Supervisor	Juan Bernardo Montaner Villalonga (Director) & Alejandro Bustamante Rangel (Director)