A landmark study reveals that decades of elite rowing and genetic predisposition combine to dramatically elevate arrhythmia risk, highlighting why not all heart risks in athletes are created equal.
Study: Atrial fibrillation in former world-class rowers: role of environmental and genetic factors. Image Credit: Ground Picture / Shutterstock
A recent European Heart Journal research paper investigates the extent to which AF occurs due to genetic predisposition and exercise burden.
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 apnoea, advancing age, structural heart disease, alcohol use, and obesity.
In comparison to non-athletes, endurance athletes were 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 of the proposed hypotheses for atrial arrhythmogenesis include inflammation, exercise-induced hemodynamic stretch, and intercurrent illnesses. The study also emphasises that cardiac remodelling, a persistent structural and electrophysiological adaptation from years of elite endurance training, is a key factor in this elevated risk.
A previous study has also 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.
Observational studies have suggested that athletes who have longer careers and perform in highly professional settings are at an elevated risk of developing AF. Hence, elite endurance athletes could be at a high risk of AF, even years after retirement from competition. The authors note that the risk may persist decades after cessation of elite sport, highlighting the long-term consequences of high-level athletic participation.
About the study
The ProAFHeart study has 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. These participants were matched based on ethnicity, gender, and age.
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. Participants in both groups had fewer differences in cardiometabolic disease and similar rates in hypertension, diabetes, and ischaemic heart disease. While none of the athletes were current smokers, approximately 25% were former smokers. In contrast, 4% of the control group were current smokers.
In terms of alcohol consumption, athletes were more prone to drink at either extreme (seldom or frequently), while the participants in the control group were more likely to drink intermittently.
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. In the case of the ECG parameters, a significant difference was found between the groups. For instance, athletes had lower heart rates, longer QRS durations, longer PQ intervals, and longer QT intervals.
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. In comparison to lifelong athletes, AF was found to be more prevalent among retired athletes. Specifically, AF prevalence was significantly higher among retired athletes (27.5%) than lifelong athletes (9.8%), though overall combined (prevalent and incident) rates were not statistically different between these groups. Within-group analysis of the control group revealed that participants with prevalent or incident AF were more likely to be male and advanced-aged. An unadjusted descriptive analysis demonstrated that participants with hypertension, diabetes, ischaemic heart disease, and prior stroke were more likely to develop AF.
Among controls, individuals who drink alcohol daily or almost daily and smoke are more likely to develop AF. However, none of the athletes in this study were current smokers. The current study observed that cardiac structure and electrocardiographic measures were similar in those with and without AF among athletes.
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.
Importantly, assessment of polygenic risk scores (PRS) showed that athletes with a high PRS were nearly four times more likely to have AF than those with a lower PRS. The proportion of individuals with high polygenic risk was similar in both the athlete and control groups, suggesting that polygenic background contributes to AF risk in both populations but does not fully explain the much higher prevalence seen in athletes.
The methods for detecting incident AF differed between groups (annual Holter monitoring and questionnaires for athletes, record linkage for controls), which may have led to underestimation of incident AF in the control group.
Conclusions
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.