BERN, SWITZERLAND. Natriuretic peptides are cardiac hormones with diuretic, natriuretic, and vasodilatory properties. Atrial natriuretic peptide (ANP) and its N-terminal prohormone are produced in the atria, whereas brain natriuretic peptide (BNP) is produced in the ventricles. Both hormones are produced in response to stretching of the walls of the heart. The stretching normally comes about through pressure caused by higher than normal fluid (blood) volume; however, in the case of atrial fibrillation (AF), the peptides are released due to the violent contractions of the walls of the atria and ventricles during an episode rather than due to volume overload. ANP is stored as a prohormone within secretory granules in the right and left atria and is secreted as an N-terminal fragment, N-terminal pro-trial natriuretic peptide (pro-ANP). Pro-ANP levels are elevated in patients with paroxysmal AF and predict the risk for recurrent episodes of AF.

A group of researchers at the University of Bern now suggests that training for and running marathons substantially increase the release of ANP and is associated with atrial enlargement and an increased risk of AF. Their study included 56 men participating in the 2010 Grand Prix of Bern, a 10-mile (16 km) race. The runners were divided into three groups:

• Group A – 22 men who had never run a marathon
• Group B – 16 men who had run 1 to 4 marathons
• Group C – 18 men who had run 5 or more marathons

The average age of the men was 42 years (range of 35 to 49 years), with men in group C tending to be older (average age of 45 years) than men in groups A and B (average age of 40 years). Men in group C had also been in training for long-distance running for a considerably longer period (18.9 years on average) than had men in group A (10.3 years) and group B (13.7 years). None of the participants had cardiovascular disease, hypertension or AF. Not surprisingly, the men in groups B and C had considerably lower average resting heart rates (51 bpm) than those in group A (61 bpm). Both the left and right atria were significantly enlarged in groups B and C with men in group B having an average left atrial volume index of 30 ml/m2 and those in group C having a volume index of 34 ml/m2 as compared to an average of 25 ml/m2 in group A. Defining left atrial enlargement as a volume index greater than 29 ml/m2, 77.8% of group C and 62.5% of group B had enlargement as compared to only 22.7% in group A.

It is also noteworthy that men in group C had substantially more ectopics (PACs and PVCs) on pre-race 24-hour Holter monitoring than did those in group A. Finally, it was observed that the veteran marathon runners in group C had significantly higher blood levels of pro-ANP at baseline than did runners in groups A and B. Pro-ANP increased significantly in every group when measured immediately following the race with group C levels being the highest. In a multiple linear regression model, average weekly endurance training hours and marathon participation contributed independently to left atrial enlargement. Interestingly, pro-ANP levels at baseline and after the race correlated only with right atrial volume, indicating the importance of volume overload of the right atrium during strenuous activities.

The researchers speculate that repetitive episodes of atrial stretching, as measured by increased pro-ANP excretion, is associated with atrial remodelling (enlargement) which, in turn, may cause atrial arrhythmias. They refer to a study involving middle-aged endurance athletes with lifetime training exposure in excess of 4500 hours. In this group, atrial enlargement was observed in 83%, and the prevalence of paroxysmal AF was 9%.
Wilhelm, M, et al. Comparison of pro-atrial natriuretic peptide and atrial remodelling in marathon versus non-marathon runners. American Journal of Cardiology, Vol. 109, No. 7, April 1, 2012, pp. 1060-65

Editor's comment: It is well established that considerable amounts of ANP are released during an AF episode (accounting for the increased frequency of urination often experienced). Thus, it is not too giant a leap of faith to suggest that the repeated stretching of arterial walls experienced during an AF episode, just like marathon running, leads to atrial enlargement and perpetuation of AF – "AF begets AF".