Elsevier

Heart Rhythm

Volume 11, Issue 1, January 2014, Pages 93-98
Heart Rhythm

Explaining the inconsistent associations of PR interval with mortality: The role of P-duration contribution to the length of PR interval

https://doi.org/10.1016/j.hrthm.2013.10.003Get rights and content

Background

There is a strong interest in PR interval as a predictor for adverse outcomes. However, inconsistent reports have emerged.

Objective

The purpose of this study was to test the hypothesis that the significance of PR interval as a predictor depends on the level of contribution of P duration to its length, a contribution that varies across populations.

Methods

We tested our hypothesis in 7501 participants from the Third National Health and Nutrition Examination Survey (NHANES III). Participants were divided into two subgroups based on the median P-duration contribution to PR interval (P duration/PR interval * 100). The risk of mortality associated with prolonged (>200 ms) and short (<120 ms) PR interval compared with normal PR interval was examined in all participants and each subgroup.

Results

P-duration contribution to the length of PR interval ranged from 30% to 90% (median 70%). During median follow-up of 13.8 years, 2541 deaths occurred. In a multivariable adjusted model, short but not prolonged PR interval was associated with mortality (hazard ratio [HR], (95% confidence interval [CI]): 1.54 (1.18, 2.00) and 1.02 (0.90, 1.16), respectively). However, in a stratified analysis by P-duration contribution to PR interval, both short and prolonged PR interval were associated with mortality in participants with high P-duration contribution (HR (95% CI):1.46 (1.10, 1.94) and 2.00 (1.34, 2.99), respectively) but not in participants with low P-duration contribution (HR (95% CI):1.53 (0.68, 3.41) and 0.99 (0.87, 1.13), respectively); interaction P = .008.

Conclusion

PR-interval associations with outcomes are dictated by the level of contribution of P duration to its length, a contribution that has a wide range and is expected to vary across populations. These findings could explain the inconsistent reports of PR-interval associations in different studies and call for caution when using PR interval in risk prediction models.

Introduction

There is a strongly emerging interest in using the electrocardiographic (ECG) PR interval as a predictor for adverse outcomes, including atrial fibrillation (AF), stroke, pacemaker implantation, and mortality.1, 2, 3, 4, 5, 6, 7, 8 The regulatory agencies have also become concerned about PR-interval prolongation resulting from cardioactive drugs.9, 10 This renewed interest in PR interval and the idea that it could serve as a simple ECG marker with potential prognostic value have been further emphasized by results from the Genome-Wide Association (GWAS) studies, which showed that the genetic background of PR interval overlaps with that of many cardiovascular diseases.11, 12, 13 In addition, PR interval has been linked to several cardiovascular risk factors.14, 15, 16

Notably, however, inconsistencies in the reported associations of prolonged PR interval with adverse outcomes started to emerge after the results were validated in different populations. In the Framingham Heart Study, prolonged PR interval was associated with an approximately 40% increase in all-cause mortality.7 However, reports from the Third National Health and Nutrition Examination Survey (NHANES-III),8 the Health, Aging, and Body Composition Study (Health ABC),6 and the Finnish Social Insurance Institution's Coronary Heart Disease Study (CHD Study)5 showed no significant associations between prolonged PR interval and all-cause mortality. Similar conflicting results have been reported regarding the usefulness of prolonged PR interval as a predictor for AF. Currently, prolonged PR interval is one of the components of the Framingham AF risk score,2 which was further validated in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES) and the Cardiovascular Health Study (CHS).3 However, prolonged PR interval did not add to the prediction of AF in the Atherosclerosis Risk in Communities (ARIC) study,17 and paradoxically short PR interval was even more predictive of AF than prolonged PR interval in a meta-analysis using data from multiple U.S. and European cohorts.4

At this time, there is no clear explanation for these inconsistencies and paradoxical associations of PR interval. Although racial and gender differences in the distribution of PR interval exist,1, 18, 19 these differences are not reflected as differences in the magnitude of associations of PR interval with outcomes.1, 3, 4, 6, 8, 17 That is to say, PR-interval associations with adverse outcomes were consistent (whether positive or negative) across all subgroups of races/ethnicities and sexes (i.e., no interaction by race/ethnicity or sex). Hence, the conflicting predictive ability of PR interval in different studies cannot be simply explained by differences in the demographic structure of these studies.

In contrast to PR interval, prolonged P duration (which is part of PR interval) has been consistently associated with adverse outcomes,1, 6, 8, 20 yet racial and gender differences in the distribution of P duration have been reported in a similar fashion as PR interval.1, 18 Therefore, we hypothesized that PR-interval associations with adverse outcomes are dependent on the level of contribution of P duration to the overall length of PR interval, a contribution that varies across populations. We tested our hypothesis using data from NHANES III.

Section snippets

Study population

Participant characteristics, ECG methodology, and ascertainment of mortality in the NHANES study have been reported elsewhere.8 Briefly, NHANES is a periodic survey of a representative sample of the civilian noninstitutionalized U.S. population. Its principal aim is to determine estimates of disease prevalence and health status of the U.S. population. The National Center for Health Statistics of the Centers for Disease Control and Prevention institutional review board approved the protocol for

Results

This analysis included 7501 participants (age 59.3 ± 13.3 years, 53% female, 51% nonwhites). Mean PR interval, P duration, and PR segment were 164.5 ± 27.1 ms, 112.4 ± 13.4 ms, and 52.2 ± 22.2 ms, respectively. The contribution of P duration to length of the PR interval ranged from 30% to 90% (median 70%). P/PR ratio was highest (i.e., more contribution of P duration to PR interval) in individuals with short PR interval and trended downward through normal and prolonged PR interval, respectively

Discussion

In this analysis from the NHANES III, we sought to provide an explanation for the emerging inconsistent and paradoxical associations of PR interval with adverse outcome. We hypothesized that PR-interval associations with adverse outcomes are dependent on the level of contribution of P duration to the overall length of PR interval, a contribution that varies across populations. We quantified the contribution of P duration to the length of PR interval using P duration/PR interval ratio * 100 as a

Conclusion

We showed that PR-interval association with mortality is dictated by the level of contribution of P duration to its length, a contribution that has a wide range and hence would vary across populations. This could explain the inconsistent results of the relationship between PR interval and adverse outcomes and calls for caution in using PR interval as a component in risk prediction models. Replicating these results in an independent population and extending the outcome to include AF are

References (25)

  • J.W. Magnani et al.

    Electrocardiographic PR-interval and adverse outcomes in older adults: the Health, Aging, and Body Composition Study

    Circ Arrhythm Electrophysiol

    (2013)
  • S. Cheng et al.

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

    JAMA

    (2009)
  • Cited by (43)

    • Analysis and classification of heart rate using CatBoost feature ranking model

      2021, Biomedical Signal Processing and Control
      Citation Excerpt :

      The selection of training and testing data set was random as manual selection makes the model more error-prone and time-consuming [26]. The training and testing dataset were shuffled to validate the extracted features because the machine learning algorithms depend on the input features and also to check the robustness of the considered machine learning classifiers [27–29]. This work's only hardware requirement is to record the ECG signals using EDAN SE 1010 PC ECG instrument.

    • Prognostic value of Goldberger's electrocardiographic criteria for left ventricular dysfunction

      2021, Journal of Electrocardiology
      Citation Excerpt :

      Therefore, the purpose of this study was to examine the risk of all-cause and cardiovascular mortality associated with Goldberger's triad in the general population using data from the Third National Health and Nutrition Examination (NHANES III) [13]. The design and conduct of NHANES III has been previously reported [14,15]. Briefly, NHANES III is a periodic survey conducted to assess disease prevalence and health status of the United States population.

    • Prevalence of P wave dispersion and interatrial block in patients with systolic heart failure and their relationship with functional status, hospitalization and one year mortality

      2018, Egyptian Heart Journal
      Citation Excerpt :

      However, there are conflicting data and uncertainty in literature regarding the association of prolonged PR interval with morbidity and mortality.3–5 A study conducted on 2541 deaths retrospectively reported that the association between PR interval and mortality was dependent on the level of P-wave duration, not the PR segment (P < 0.008).3 Many other studies concluded that no increased mortality among individuals with prolonged PR interval (>200 ms), whereas it was the contribution of the P-wave duration that was associated with morbidity and mortality.4,5

    View all citing articles on Scopus
    View full text