Risk of atrial fibrillation as a function of the electrocardiographic PR interval: Results from the Copenhagen ECG Study
Introduction
The electrocardiographic PR interval (or PQ interval) reflects the time, measured in milliseconds, required for an electrical impulse to propagate from the atrial myocardium surrounding the sinus node through the atrioventricular (AV) node to the Purkinje fibers. Several factors affecting impulse propagation at these sites might influence PR interval duration, including changes in vagal tone, ischemic heart disease, various medications, genetic variation in genes encoding cardiac ion channels or related proteins, and degenerative conduction diseases.
A prolonged PR interval has been associated with an increased risk of coronary heart disease, heart failure, pacemaker implantation, and death. In addition, a prolonged PR interval confers an increased risk of atrial fibrillation (AF),1, 2, 3, 4 and the PR interval is a component of the Framingham risk score for AF.5
AF is the most common sustained cardiac arrhythmia and is responsible for considerable morbidity and mortality, including an increased risk of stroke, dementia, and heart failure.6
PR interval and AF both appear to have a substantial heritable component.7, 8 Recent genetic studies have revealed a number of genomic loci that are associated with both PR interval duration and AF.9, 10 Interestingly, genetic loci associated with both shortening and prolongation of PR interval confers an increased risk of AF. Thus, in contrast to the current perception that a long PR interval poses a risk of AF, these findings suggest that individuals with a short PR interval might also be at risk. However, to the best of our knowledge, this has not been reported previously.
Therefore, we sought to determine the relation between both short and long PR intervals and the risk of AF. Such knowledge could lead to a better understanding of the pathophysiology underlying AF and potentially could contribute to improvement of current risks scores for AF.
Section snippets
Study population
In the greater region of Copenhagen, Denmark, the vast majority of general practitioners refer their patients to one core facility (Copenhagen General Practitioners’ Laboratory [CGPL]) for clinical tests, such as biochemistry and electrocardiogram (ECG) recordings. The present study population consists of all individuals who had an ECG recorded at CGPL from 2001 to 2010. Individuals were excluded for reasons shown in Figure 1.
Further details on the ECG study population, including a comparison
Results
The greater region of Copenhagen has a current population of 1.18 million citizens. Among them, 326,959 individuals (~28%) had 1 or more ECGs recorded at CGPL during the 10-year period from 2001 to 2010. Of the individuals referred for ECG recording, a total of 288,181 (86%) fulfilled the study inclusion criteria (Figure 1). Selected baseline characteristics of the study population are listed in Table 1.
Discussion
In a large population of primary care patients, we investigated the association between PR interval duration and risk of AF and found a J-shaped relationship (Figure 3).
We previously reported that patients with early-onset AF have longer PR intervals compared with healthy controls.13 In the Framingham Heart Study, it was shown that first-degree AV block (PR interval > 200 ms) was associated with a multivariable-adjusted HR of 2.06 (95% CI 1.36–3.12) for AF compared with individuals without
Conclusion
Investigating a primary care population of more than 280,000 individuals, we found that longer PR intervals conferred an increased risk of AF for both women and men. With respect to short PR intervals, women but not men had a statistical significant increased risk of developing AF.
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This study was supported by the University of Copenhagen, the Danish National Research Foundation, The Danish Council for Independent Research (Grant No 11-107456), The John and Birthe Meyer Foundation, The Foundation of 17-12-1981, The Beckett Foundation, and the Copenhagen Medical Society (DMSK).