A landmark study has revealed that decades of elite rowing, combined with genetic predisposition, significantly elevate the risk of atrial fibrillation (AF), underscoring that not all heart risks in athletes are created equal. This research, published in the European Heart Journal, investigates the extent to which AF occurs due to genetic predisposition and exercise burden.
The study, titled “Atrial Fibrillation in Former World-Class Rowers: Role of Environmental and Genetic Factors,” highlights the complex interplay between intense physical activity and genetic factors in the development of AF among athletes. This finding is crucial as it challenges the conventional understanding of heart health in athletes.
Atrial Fibrillation in Athletes
AF is a type of heart rhythm problem that increases the risk of stroke and heart failure. Several studies have identified risk factors associated with AF, including hypertension, obstructive sleep apnea, advancing age, structural heart disease, alcohol use, and obesity. In contrast to non-athletes, endurance athletes are found to be at a higher risk of developing AF.
Although several mechanisms have been proposed to explain why athletes are susceptible to AF, the precise cause remains elusive. Some hypotheses for atrial arrhythmogenesis include inflammation, exercise-induced hemodynamic stretch, and intercurrent illnesses. The study also emphasizes that cardiac remodeling, a persistent structural and electrophysiological adaptation from years of elite endurance training, is a key factor in this elevated risk.
A previous study has hypothesized that athletic training may activate genes leading to AF development. For instance, truncating variants in the TTN gene were found to be associated with an early onset of AF. AF heritability explains why many younger individuals with no other risk factors develop the condition. More research is required to understand the precise genetic predisposition that regulates the incidence of AF in younger athletes.
About the Study
The ProAFHeart study focused on estimating AF prevalence in elite retired rowers and investigated whether this increase is linked to genetic predisposition. Former elite rowers who competed at a national, world championship, or Olympic level between 1960 and 1992 were recruited. These participants, aged between 45 and 80 years, were identified from Australian Rowing History. A matched control group at a ratio of 1:100 was extracted from the UK Biobank.
Participants with AF were identified from the UK Biobank based on the date of cardiac magnetic resonance imaging (CMR) and electrocardiogram (ECG). All participants provided information about exercise regimes during the years of international competitive rowing and after retirement via a questionnaire. Participants who continued to exercise vigorously after their rowing career were referred to as Lifelong Athletes.
Genetic analysis was performed using peripheral blood samples. Based on the American College of Medical Genetics and Genomics (ACMG), variants were classified as pathogenic, likely pathogenic (LP), variants of uncertain significance (VUS), likely benign, and benign. In addition, a polygenic risk score for AF (AF-PRS) was calculated, quantifying each individual’s background genetic susceptibility to AF.
Study Findings
A total of 121 former elite rowers, with a mean age of 62 years, were recruited and followed for a median of 4.4 years. The study cohort comprised 74% males and 23 former Olympians, all of whom were of White ethnicity. Compared to the control group, retired athletes performed more exercise, were leaner, taller, had greater bone mineral density, and had marginally lower systolic and diastolic blood pressures.
While none of the athletes were current smokers, approximately 25% were former smokers. In contrast, 4% of the control group were current smokers.
The current study observed that, compared to the control group, strokes were three times more prevalent among athletes. However, absolute numbers were low, with 4 of 121 athletes and 128 of 11,495 controls affected. Additionally, the cardiac volumes of the athletes, as measured by CMR, were significantly larger than those of the control group participants. However, no difference in left ventricular ejection fraction was observed in both groups.
AF prevalence was higher among former elite athletes than control subjects. The incidence of AF over a four-year follow-up period was also greater in the study group compared to the control group. Survival analysis revealed that athletes without a history of AF at baseline were 2.8 times more likely to develop incident AF.
The authors performed sensitivity analyses to account for possible selection bias, confirming that the excess prevalence of AF in athletes persisted even under conservative assumptions.
Sequencing of 24 cardiomyopathy genes indicated the presence of 2.7% pathogenic variants. Three athletes carried likely pathogenic variants in cardiomyopathy genes. Only the athlete with a JUP (plakoglobin) variant had AF; the two athletes with PKP2 (plakophilin-2) and DSP (desmoplakin) variants did not have AF. The overall yield of rare, disease-causing variants was low, and there was no difference in frequency between those with and without AF.
Conclusions and Future Directions
The current study demonstrated that former athletes undergo cardiac remodeling that persists decades after retirement, which may increase the prevalence and incidence rates of AF. In contrast to identifying variants linked to inherited cardiomyopathies, background genetic variation could be more relevant to predicting AF risks. Future studies involving a more diverse and inclusive athletic population, particularly among women, are warranted.
The findings suggest that polygenic risk scores may be useful in the future for risk stratification and screening policies among athletes. As the understanding of genetic predispositions and their interaction with intense physical activity evolves, it could lead to more tailored health monitoring and preventive strategies for athletes.
