Towards improved risk prediction of incident atrial fibrillation and progression of atrial fibrillation

This general aim of the present thesis was to improve risk prediction of incident AF and progression of atrial fibrillation (AF). First we investigated markers to predict incident AF. In chapter 2 we showed the relation of renal dysfunction with incident AF and the as- sociation with cardiovascular morbidity and mortality by using the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. Our analyses showed that increased albumin excretion and not estimated glomerular filtration rate, as is most often used in clinical practice, was associated with incident AF. In chapter 3 we evaluated metabolic profiling in the relation to incident AF in the Framingham Heart Study. In contrast to previous studies, we observed no relation between small-molecule metabolites in diverse biological systems and incident AF. For prediction of incident AF but even more for progression of AF assessment of the actual severity of structural remodelling is es- sential. In chapter 4 we aimed to improve assessment of the severity of atrial structural remodelling using body surface ECG mapping to measure P wave complexity. We showed that a higher number of peaks in the P-wave and larger P-wave terminal force in lead V1 can differentiate between patients with and without a history of AF, i.e. help to assess severity of atrial remodelling. In the last part of this thesis we assessed the prevalence and predictors of AF progression in different patient populations. In Chapter 5 (Young AF cohort) we investigated young onset AF patients (mean age 49 years). Interestingly, even in this young population risk factors and comorbidities were present in 89% of the patients. AF progression to permanent AF and cardiovascular events occurred in 2% and 2.4% per year, respectively. Cardiovascular events increased after AF progression had occurred. Predictors in this population included PR interval and left ventricular hy- pertrophy. In Chapter 6 (AF-Risk cohort) we included patients (mean age 60 years) with short-lasting AF. AF progression occurred in 13% of patients in this group during 1-year follow-up. An increased left atrial volume, elevated NT-proBNP and lower PAI-1, possibly as sign of inflammation, were associated with AF progression. Also in this study patients with AF progression had a higher event rate during follow-up. Finally, since nowadays there is an increasing awareness that sex is a major determinant of the incidence, etiol- ogy, and clinical presentation of AF, one chapter was about sex differences. Until now, women are not only underrepresented in major AF trials, in addition, data on clinical profile and outcome in young AF patients is limited. Therefore we aimed to investigate the clinical profile, AF progression rate and cardiovascular outcome between sexes in patients with young-onset AF in Chapter 7 (Young AF cohort).