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The Role of Inflammation in the Pathophysiology of Artrial Fibrillation

Kristoffer Mads Aaris Henningsen

Summary 

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Increasing evidence has suggested that inflammation might play a role in the pathophysiology of AF and inflammation has been associated with AF in cross-sectional studies. 

The aim of this PhD thesis was to investigate the role of inflammation in the pathophysiology of AF. We studied the association between AF and levels of inflammatory markers in peripheral blood and between AF and single nucleotide polymorphisms (SNPs) in inflammatory genes. 

In the first part we investigated the association between levels of inflammatory markers in peripheral blood and AF in two different cohorts. We measured the commonly used inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) and Interleukin-6 (IL- 6), but also the emerging new inflammatory marker YKL-40. The first cohort consisted of patients with persistent AF treated with electrical cardioversion (CV). We found that baseline IL-6 was an independent predictor of recurrent AF after electrical CV. We also found that patients with AF had significantly elevated levels of YKL-40, but YKL-40 was not a significant predictor of successful CV to sinus rhythm (SR). The second cohort consisted of patients with AF treated with radio-frequency catheter ablation (RFA). We found that the patients who remained in SR after the procedure had significantly lower values of both IL-6 and hs-CRP at baseline before ablation. Furthermore, the baseline level of IL-6 prior to ablation was an independent predictor of recurrent AF.

 In the second part we investigated the association between SNPs in inflammatory genes and AF. We investigated 7 promoter SNPs in commonly investigated inflammatory genes and 10 SNPs in the Chitinase-3-like-1 (CHI3L1) gene coding for YKL-40. We compared a cohort of young patients with lone AF and a cohort of elderly AF patients to a control group of healthy volunteers. We found that a promoter SNP (–131C G) in CHI3L1 (rs4950928) was associated with a significantly increased risk of AF (OR 1.69; 95%CI 1.1-2.5) in young patients. We were not able to show any association between SNPs in the 7 investigated inflammatory genes in any of the cohorts.

 In conclusion, we find that the levels of inflammatory markers in peripheral blood are associated to both AF and to the recurrence rate of AF after electrical CV and RFA. Furthermore, we find an association between a SNP in the CHI3L1 gene and lone AF in young patients.