Epicardial Fat Volume and the Risk of Atrial Fibrillation in the General Population Free of Cardiovascular Disease

During the past years, several clinical studies demonstrated associations of the amount of epicardial fat (i.e., adipose tissue surrounding the myocardium) with the burden of atrial fibrillation (AF) and outcomes after AF ablation. However, as was recently pointed out in major reviews on epicardial fat and AF, prospective data with long follow-up periods in individuals free of cardiovascular disease remains scarce. These insights are crucial to improve our understanding of the potentially causal role of epicardial fat in the development of AF as the results from healthy populations are less susceptible to confounding by coexisting cardiovascular disease, such as coronary disease and heart failure.
We used data from 1,990 participants from the Dutch prospective population-based Rotterdam Study cohort who underwent nonenhanced multidetector computed tomography and were free of cardiovascular disease. We quantified epicardial fat volume on the computed tomography examinations using previously published methods. Participants were thoroughly followed-up for AF until 2014, using 3 methods that have been described in detail previously. Briefly, these included repeated electrocardiograms in the study setting, continuous monitoring of general practitioners records, and standardized evaluation of the national medical registry of all hospital discharge diagnoses. The Rotterdam Study has been approved by the Medical Ethics Committee of the Erasmus Medical Center according to the “Population Screening Act: Rotterdam Study,” executed by the Ministry of Health, Welfare, and Sports of the Netherlands. All participants provided written informed consent. The mean age of the study participants was 68.8 years, and 54.9% of the participants were women.The median epicardial fat volume was 100 ml. During 15,794 person-years of follow-up, 142 participants developed AF. Larger amounts of epicardial fat were associated with an increased risk of AF. Additional adjustment for coronary calcification and left atrial diameter slightly attenuated this association. Persons in the upper quartile had a 2-fold increased risk of AF compared with those in the lowest quartile. Correlations between epicardial fat volume and markers of adiposity were moderate. Despite adjustment for all 4 markers of adiposity, epicardial fat volume remained independently associated with risk of AF. There was no significant effect modification by traditional cardiovascular risk factors.
In summary, we found an association of epicardial fat with AF in individuals free of cardiovascular disease that was independent of traditional cardiovascular risk factors, coronary atherosclerosis, left atrial size, and various measures of adiposity. Therefore, it is unlikely that our findings are explained by preexisting overt or subclinical heart disease or by systemic effects of adipose tissue.
Strengths of this study include the populationbased setting, the longitudinal assessment of AF, and the use of standardized computed tomography-based procedures to quantify epicardial fat. Potential limitations include the possibility of underdiagnosis of asymptomatic AF despite the rigorous AF casefinding strategy. Nonetheless, this would most likely bias our results toward the null. Moreover, the vast majority of participants are older white individuals, potentially limiting generalizability of our findings to other populations.
Potential mechanisms underlying the relation between epicardial fat and AF include direct fatty infiltration into the myocardium or secretion of factors with inflammatory and fibrotic properties by epicardial fat, both facilitating arrhythmogenesis. Yet, further elucidation of these specific pathophysiological pathways is required to translate this into potential therapeutic interventions.
From a clinical standpoint, it is noteworthy that the amount of epicardial fat can be derived from any electrocardiogram-triggered, nonenhanced cardiac computed tomography examination. Information on epicardial fat volume can be easily obtained with dedicated software and thereby provide valuable insight into the patients’ risk of developing AF without additional testing.