Risk of atrial fibrillation as a function of the electrocardiographic PR interval: Results from the Copenhagen ECG Study

doi:10.1016/j.hrthm.2013.04.012

Heart Rhythm

Volume 10, Issue 9, September 2013, Pages 1249-1256

https://doi.org/10.1016/j.hrthm.2013.04.012 Get rights and content

Background

Prolongation of the PR interval has been associated with an increased risk of incident atrial fibrillation (AF).

Objective

To determine if there was a nonlinear relation between PR interval duration and the risk of AF.

Methods

We included 288,181 individuals, corresponding to one third of the population in the greater region of Copenhagen. These individuals had a digital electrocardiogram (ECG) recorded in a general practitioner’s core facility from 2001 to 2010. Data on drug use, comorbidity, and outcomes were collected from Danish registries.

Results

During a median follow-up period of 5.7 years, 11,087 developed AF. Having a PR interval ≥95th percentile (≥196 ms for women, ≥204 ms for men) was associated with an increased risk of AF as evidenced by a multivariable-adjusted hazard ratio (HR) of 1.18 (95% confidence interval [CI] 1.06–1.30, P = .001) for women and 1.30 (1.17–1.44, P < .001) for men compared with the respective reference groups (PR interval between 40th and 60th percentile). Having a short PR interval <5th percentile (≤121 ms for women, ≤129 ms for men) was also associated with an increased risk of AF for women (HR 1.32, 95% CI 1.12–1.56, P = .001), but this was not significant for men (HR 1.09, 95% CI 0.92–1.29, P = .33).

Conclusion

In this large ECG study, we found an increased risk of AF for longer PR intervals for both women and men. With respect to short PR intervals, we also observed an increased risk of AF for women.

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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PR prolongation as a predictor of atrial fibrillation onset: A state-of-the-art review
2024, Current Problems in Cardiology
First-degree atrioventricular block (1-AVB), characterized by a PR interval exceeding 200 milliseconds, has traditionally been perceived as a benign cardiac condition. Recently, this perception has been challenged by investigations that indicate a potential association between PR prolongation and an elevated risk of atrial fibrillation (AF). To consolidate these findings, we performed a comprehensive review to assess the available evidence indicating a relationship between these two conditions. We searched MEDLINE and EMBASE databases as well as manually searched references of retrieved articles. We selected 18 cohort studies/meta-analyses involving general and special populations. Consistent findings across expansive cohort studies reveal that incremental increases in the PR interval may serve as an independent risk factor for AF. However, our analyses underscore the need for further research into the association between 1-AVB, defined by a specified PR interval cutoff, and the risk of AF.
ECG predictors of AF: A systematic review (predicting AF in ischaemic stroke-PrAFIS)
2024, Clinical Neurology and Neurosurgery
In 25% of patients presenting with embolic stroke, a cause is not determined. Atrial fibrillation (AF) is a commonly identified mechanism of stroke in this population, particularly in older patients. Conventional investigations are used to detect AF, but can we predict AF in this population and generally? We performed a systematic review to identify potential predictors of AF on 12-lead electrocardiogram (ECG).
We conducted a search of EMBASE and Medline databases for prospective and retrospective cohorts, meta-analyses or case-control studies of ECG abnormalities in sinus rhythm predicting subsequent atrial fibrillation. We assessed quality of studies based on the Newcastle-Ottawa scale and data were extracted according to PRISMA guidelines.
We identified 44 studies based on our criteria. ECG patterns that predicted the risk of developing AF included interatrial block, P-wave terminal force lead V1, P-wave dispersion, abnormal P-wave-axis, abnormal P-wave amplitude, prolonged PR interval, left ventricular hypertrophy, QT prolongation, ST-T segment abnormalities and atrial premature beats. Furthermore, we identified that factors such as increased age, high CHADS-VASC, chronic renal disease further increase the positive-predictive value of some of these parameters. Several of these have been successfully incorporated into clinical scoring systems to predict AF.
There are several ECG abnormalities that can predict AF both independently, and with improved predictive value when combined with clinical risk factors, and if incorporated into clinical risk scores. Improved and validated predictive models could streamline selection of patients for cardiac monitoring and initiation of oral anticoagulants.
Incidence and determinants of atrial fibrillation in patients with wild-type transthyretin cardiac amyloidosis
2023, International Journal of Cardiology
Data on the incidence and factors associated with de novo atrial fibrillation (AF) in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is limited. We described the incidence and factors associated with de novo AF in patients diagnosed with ATTRwt-CA to drive tailored arrhythmia screening.
Multicenter, retrospective, observational cohort study performed in six referral centers for CA. All consecutive patients diagnosed with ATTRwt-CA between 2004 and 2020 with >6-month follow up (FU) were enrolled and divided into three groups according to presence of AF: (1)patients with ‘known AF’; (2)patients in ‘sinus rhythm’ and (3)patients developing ‘de novo AF’ during FU. Incidence and factors associated with AF in patients with ATTRwt were the primary outcomes.
Overall, 266 patients were followed for a median of 19 [11−33] months: 148 (56%) with known AF, 84 (31.6%) with sinus rhythm, and 34 (12.8%) with de novo AF. At Fine-Gray competing risk analysis to account for mortality, PR (sub-distribution hazard ratio [SHR] per Δms: 1.008, 95% C.I. 1.001–1.013, p = 0.008), QRS (SHR per Δms: 1.012, 95% C.I. 1.001–1.022, p = 0.046) and left atrial diameter ≥ 50 mm (SHR: 2.815,95% C.I. 1.483–5.342, p = 0.002) were associated with de novo AF. Patients with at least two risk factors (PR ≥ 200 ms, QRS ≥ 120 ms or LAD≥50 mm) had a higher risk of developing de novo AF compared to patients with no risk factors (HR 14.918 95% C.I. 3.242–31.646, p = 0.008).
At the end of the study almost 70% patients had AF. Longer PR and QRS duration and left atrial dilation are associated with arrhythmia onset.
Research progress on predicting atrial fibrillation recurrence after radiofrequency ablation based on electrocardiogram-related parameters
2023, Journal of Electrocardiology
Atrial fibrillation (AF) is the most common arrhythmia. It is associated with increased stroke risks, thromboembolism, and other complications, which are great life and economic burdens for patients. In recent years, with the maturity of percutaneous catheter radiofrequency ablation (RFA) technology, it has become a first-line therapy for AF. However, some patients still experience AF recurrence (AFR) after RFA, which can cause serious consequences. Therefore, it is critical to identify appropriate parameters that are predictive of prognosis and to be able to translate the parameters easily into the clinical setting. Here, we reviewed possible predicting indicators for AFR, focusing on all the electrocardiogram indicators, such as P wave duration, PR interval and so on. It may provide valuable information for guiding clinical works.
Epidemiology and Outcomes Associated with PR Prolongation
2023, Cardiology Clinics
Association between primary care electrocardiogram markers and Alzheimer's disease
2023, Journal of the Neurological Sciences
The association between common electrocardiogram (ECG) markers and Alzheimer's disease has been scarcely investigated, and it is unknown if ECG markers can improve risk prediction. Thus, we aimed to examine the association between common ECG markers and Alzheimer's disease in a large population.
We studied the association between ECG markers and Alzheimer's disease using Cox models with adjustment for age, sex, and comorbidities using a large primary care population of patients aged 60 years or more.
We followed 172,236 subjects for a median of 7.5 years. Increased PR interval (hazard ratio for PR > 188 ms: 0.76 [95% confidence interval: 0.69–0.83, p < 0.001) and increased QTc interval (hazard ratio for QTc = [426;439]: 0.90 [0.83–0.98], p = 0.02) were associated with a decreased rate of Alzheimer's disease. A positive Sokolow-Lyon index >35 mm (1.22 [1.13–1.33], p < 0.001) and increased T-wave amplitude >4.1 mm (1.15 [1.04–1.27]) were associated with an increased rate of Alzheimer's disease. Upon addition of ECG markers to a reference model, 10-year prediction area under the receiver-operator characteristics curve (AUC) improved by 0.39 [0.06–0.67] %-points. The 10-year absolute risk of Alzheimer's disease was 6.5% and 5.2% for an 82-year old female and a male, respectively, with a favorable ECG, and 12% and 9.2%, respectively, with an unfavorable ECG, almost twice as high.
We identified several common ECG markers which were associated with Alzheimer's disease, and which improved risk prediction for Alzheimer's disease.

View all citing articles on Scopus

: 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).

View full text

Risk of atrial fibrillation as a function of the electrocardiographic PR interval: Results from the Copenhagen ECG Study

Background

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Results

Discussion

Conclusion

Lancet

Cardiol Clin

Am J Cardiol

Am J Med

J Clin Epidemiol

Am Heart J

J Clin Epidemiol

Am J Hypertens

Heart Rhythm

Coronary heart disease in seven countries. XVI. The electrocardiogram in prediction of five-year coronary heart disease incidence among men aged forty through fifty-nine

Circulation

Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block

JAMA

Ethnic distribution of ECG predictors of atrial fibrillation and its impact on understanding the ethnic distribution of ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study

Stroke

First-degree atrioventricular block is associated with heart failure and death in persons with stable coronary artery disease: data from the Heart and Soul Study

Eur Heart J

Familial aggregation of atrial fibrillation: a study in Danish twins

Circ Arrhythm Electrophysiol

Several common variants modulate heart rate, PR interval and QRS duration

Nat Genet

Genome-wide association study of PR interval

Nat Genet