Association of early repolarization pattern on ECG with risk of cardiac and all-cause mortality: a population-based prospective cohort study (MONICA/KORA)

Abstract

Background: Early repolarization pattern (ERP) on electrocardiogram was associated with idiopathic ventricular fibrillation and sudden cardiac arrest in a case-control study and with cardiovascular mortality in a Finnish community-based sample. We sought to determine ERP prevalence and its association with cardiac and all-cause mortality in a large, prospective, population-based case-cohort study (Monitoring of Cardiovascular Diseases and Conditions [MONICA]/KORA [Cooperative Health Research in the Region of Augsburg]) comprised of individuals of Central-European descent.

Methods and findings: Electrocardiograms of 1,945 participants aged 35-74 y, representing a source population of 6,213 individuals, were analyzed applying a case-cohort design. Mean follow-up was 18.9 y. Cause of death was ascertained by the 9th revision of the International Classification of Disease (ICD-9) codes as documented in death certificates. ERP-attributable effects on mortality were determined by a weighted Cox proportional hazard model adjusted for covariables. Prevalence of ERP was 13.1% in our study. ERP was associated with cardiac and all-cause mortality, most pronounced in those of younger age and male sex; a clear ERP-age interaction was detected (p = 0.005). Age-stratified analyses showed hazard ratios (HRs) for cardiac mortality of 1.96 (95% confidence interval [CI] 1.05-3.68, p = 0.035) for both sexes and 2.65 (95% CI 1.21-5.83, p = 0.015) for men between 35-54 y. An inferior localization of ERP further increased ERP-attributable cardiac mortality to HRs of 3.15 (95% CI 1.58-6.28, p = 0.001) for both sexes and to 4.27 (95% CI 1.90-9.61, p<0.001) for men between 35-54 y. HRs for all-cause mortality were weaker but reached significance.

Conclusions: We found a high prevalence of ERP in our population-based cohort of middle-aged individuals. ERP was associated with about a 2- to 4-fold increased risk of cardiac mortality in individuals between 35 and 54 y. An inferior localization of ERP was associated with a particularly increased risk. Please see later in the article for the Editors' Summary.

Figure 1. Representative examples of ERP from our study population.

(A) shows a slurring morphology, whereas a notching morphology predominates in (B) and (C). Arrows point to leads where ERP can be identified most clearly.

Figure 2. ERP effects on cardiac mortality.

(A) HRs and CIs for ERP in any localization. (B) HRs and CIs for the analysis restricted to ERP in an inferior localization. In both (A) and (B), the symbols illustrate the effect size as derived from an age-stratified analysis in younger (35–54 y), middle-aged (55–64 y), and older (65–74 y) participants. Comparing (A) and (B), the ERP-attributable effect is more pronounced if localized in inferior leads. The lower panels show Kaplan-Meier curves for cardiac mortality depending on the presence of ERP and sex in the subgroup of younger individuals (35–54 y). (C) Kaplan-Meier curves for ERP in any localization. (D) Kaplan-Meier curves for ERP in an inferior localization. Men with ERP show the highest cumulative hazard. The effect of ERP on cardiac mortality is stronger in men and outweighs the sex-attributable effect. ERP-attributable effects tend to start earlier in men than in women. Again, effects are stronger, restricting the analysis to an inferior localization of ERP. p-Values in (C and D) were derived by a weighted Cox proportional hazards model. The numbers of individuals at risk are listed below each Kaplan-Meier plot.