Author + information
- †Lankenau Institute for Medical Research, Wynnewood, Pennsylvania
- ‡Jefferson Medical College, Philadelphia, Pennsylvania
- ↵∗Reprint requests and correspondence:
Dr. Peter R. Kowey, Lankenau Medical Center, 100 East Lancaster Avenue, Medical Office Building East, Suite 356, Wynnewood, Pennsylvania 19096.
The world is full of obvious things, which nobody by any chance ever observes.
— Sherlock Holmes (1)
It is fair to say that atrial fibrillation (AF) has reached epidemic proportions. With an aging population and improved survival with concomitant conditions, the prevalence of AF is predicted to increase dramatically in the next several decades (2), with profound implications for patients’ health, quality of life, and the global economy. It is therefore important to monitor the epidemiology of this disease, to identify novel and reversible risk factors and track the impact of AF treatments at a population level.
In this issue of the Journal, Vermond et al. (3) present a large (n = 8,256), prospective cohort study evaluating the incidence, risk factors, and complications of AF in a contemporary population of patients, 28 to 75 years old, ostensibly free of AF at baseline. The average length of follow up was 9.7 ± 2.3 years. The study had the advantage of a captured population with excellent follow-up and confirmable rhythm diagnosis. The most important finding of this study is that the incidence rate of AF (3.3/1,000 patient-years) was comparable to previous epidemiological data, despite a relatively young study population (mean age: 49 ± 13 years) with albuminuria. Earlier analyses of AF incidence density over time indicated that it remained stable between the mid-1990s to the mid-2000s, but that AF prevalence has continued to rise (4). What are the most important contributors to this important epidemiological development?
In their contemporary patient population, Vermond et al. (3) identified obesity as a significant risk factor for incident AF, with a 45% increased risk for every 5 kg/m2 increase in body mass index. They propose that obesity is likely a prominent factor contributing to the significant incidence of AF. A recent study by Nystrom et al. (5) corroborated this finding but added that being overweight (body mass index: 25.0 to 29.9 kg/m2), rather than obese, was a significant risk factor only when it was part of the metabolic syndrome. Animal studies suggest that obesity directly contributes to the AF substrate by altering atrial electrical and structural remodeling (6).
Obesity also could increase the risk of AF by its association with risk factors that are not traditionally included in epidemiological studies. Pericardial fat has been identified as a risk factor for the increased prevalence and severity of AF (4), perhaps because it is metabolically active and produces inflammatory cytokines (4). Similarly, patients with obstructive sleep apnea (OSA) have roughly a 4-fold increased risk of developing AF (4). It is not yet clear whether OSA is a causal risk factor or part of a larger risk profile, but the finding that continuous positive pressure ventilation reduces the recurrence rates of AF in these patients suggests a possible pathogenic role (7). Unfortunately, data on OSA or pericardial fat were not available in the study by Vermond et al. (3) and are not commonly reported in the literature.
There is a ray of hope in the midst of the obesity and AF epidemics. Studies have demonstrated that physician-led weight loss programs can significantly reduce the number of AF episodes, as well as the symptom burden and severity in obese patients with AF (8,9). Such studies indicate that the medical community will likely need to take a much more active role in facilitating risk factor modification to slow the rising incidence of AF globally.
Vermond et al. (3) showed that despite recent advances in the treatment of AF and cardiovascular disease, AF remains strongly associated with adverse cardiovascular outcomes and mortality. Stroke, cardiovascular disease, and heart failure remained the most significant complications of AF in this study.
A prevailing theory to explain why mortality and complication rates of AF have remained static over time is that we are not intervening early enough in the course of the disease. This may partly explain why large trials such as AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) (10) demonstrated no significant difference in mortality benefit between rate and rhythm control strategies in AF (11). In addition, the antiarrhythmic drugs currently available for AF have limited efficacy and considerable side effects. Ongoing large-scale trials such as the CABANA (Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation) trial (NCT00911508) will provide information on whether catheter ablation is a better therapeutic choice than antiarrhythmic drugs. The EAST (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) will also elucidate whether earlier rhythm control strategies improve AF outcomes (NCT01288352).
We also suspect that we have not nudged the needle with regard to outcomes because we treat AF as a homogenous disease when in fact it has a diverse pathogenesis. Until we have better insight into operative mechanisms in individual patients, it is unlikely that any of the treatments we devise will alter the inevitable outcome of this complex disease.
Another factor contributing to the static trends of AF-related mortality and complications is compliance. This includes patients adhering to treatment regimens and physicians following recommended evidence-based practice guidelines. It is a factor rarely mentioned in the current literature. The World Health Organization (12) reported that medication adherence in developed countries is only 50%, and this percentage is presumed to be worse in developing countries. The World Health Organization emphasized the importance of improving patient adherence and claimed that this factor is likely to have a greater impact on population health than any advance in alternative or improved treatments (12). Unfortunately, no data are available on the treatment regimens or patient compliance levels in the study by Vermond et al. (3). Using data from large registries is an effective way of monitoring treatment trends over time and has the advantage of being more widely applicable to the general population. Traditional observational studies such as that of Vermond et al. (3) are limited by the restricted population in a single center. In addition, the method of AF detection in this study was inadequate. Periodic sampling of electrocardiograms grossly underestimates the burden of AF compared with long-term monitoring (13).
In conclusion, we congratulate the authors on producing a robust epidemiological study confirming the incidence, risk factors, and complications of AF in a selected, young, and contemporary population of patients. Their findings once again highlight the importance of identifying novel and reversible risk factors for AF, so that we can increase our efforts to prevent this disease. Moreover, the continued risk of AF-associated mortality and cardiovascular complications demonstrated in this study emphasizes the need to optimize evidence-based treatment guidelines and to encourage physicians to implement these guidelines where appropriate. We must not lose sight of the fact that despite our best efforts to modify reversible risk factors, AF will continue to emerge in older adults as a result of aging-induced fibrosis. Nevertheless, initiatives to improve patient adherence to long-term prevention and treatment regimens may help to ease the significant societal burden of AF.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Kowey serves on the steering committee for the CABANA trial. Dr. Robinson has reported that she has no relationships relevant to the contents of this paper to disclose.
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