In a population-based cohort study of middle-aged people in Central Europe, Stefan Kääb and colleagues find an association between electrocardiographic early repolarization pattern and mortality risk.
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.
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
Cardiovascular diseases—disorders that affect the heart and the circulation—are the leading cause of death in the developed world. About half of cardiovascular deaths occur when the heart suddenly stops pumping (sudden cardiac arrest). The muscular walls of the four heart chambers contract in a set pattern to pump blood around the body. The heart's internal electrical system controls the rate and rhythm of these contractions and, if this system goes wrong, an abnormal heart beat or “arrhythmia” develops. Some arrhythmias—in particular, ventricular fibrillation in which the walls of the two lower heart chambers quiver or “fibrillate” instead of pumping—can cause sudden cardiac arrest and immediate loss of consciousness. Death follows within minutes in 95% of cases but immediate cardiopulmonary resuscitation (CPR; chest compression to pump the heart and inflation of the lungs by mouth-to-mouth resuscitation) can keep a person alive until a defibrillator can be used to restore the normal heart beat. People who survive sudden cardiac arrest can be given anti-arrhythmia drugs or have a pacemaker implanted to stabilize their heart beat.
Why Was This Study Done?
The beating heart generates tiny electric waves that can be detected by electrodes on the skin. The pattern of these waves (an electrocardiogram or ECG) provides information about the heart's health. One wave pattern that is often seen on ECGs is the “early repolarization pattern” (ERP), which some studies suggest is associated with an increased risk of cardiac death. Here, the researchers investigate the prevalence of ERP (the proportion of a population with ERP) and its association with death from heart-related problems (cardiac mortality) and from any cause (all-cause mortality) in the MONICA/KORA prospective, population-based case-cohort study. The MONICA Project (MONitoring of Trends and Determinants in CArdiovascular Disease) has studied cardiovascular disease in 10 million people in 21 countries; KORA denotes the study done in the Augsburg region of Germany. In a prospective study, specific baseline characteristics of the study's participants are determined and the participants are followed to see who experiences a predefined outcome. A case-cohort study investigates a randomly selected subcohort (subgroup) of the original participants of a study and any participants who experience the predefined outcome instead of all the participants.
What Did the Researchers Do and Find?
The researchers selected 1945 MONIKA/KORA participants aged 35–74 years from a source population of about 6,000 people using a case-cohort study design. They analyzed the ECGs (recorded in 1984–1985 or 1989–1990) of this subcohort and ascertained the cause of death for those participants who died during the 18.9 year average follow-up. The overall prevalence of ERP in the study was 13.1%, report the researchers, and ERP was associated with cardiac mortality, particularly among younger and male participants. Specifically, among men and women aged 35–54 years, having ERP was associated with a nearly doubled risk of cardiac death. Among men aged 35–54 years, having ERP was associated with an increase in the risk of cardiac death by 2.65-fold. An ERP localized to the bottom of the heart (inferior localization) was associated with an increased risk of cardiac death among both sexes by more than 3-fold and among men by more than 4-fold in this age group. Finally, ERP was also significantly associated with an increased risk of all-cause mortality but less strongly than with cardiac mortality.
What Do These Findings Mean?
These findings suggest that the prevalence of ERP among the middle-aged people in the MONICA/KORA study is high (and somewhat higher than previously reported). They also show a clear association between ERP and the risk of cardiac death among 35–54-year-old people, particularly among men, but because of the study design, these findings do not show that ERP actually causes cardiac death; it could simply be a susceptibility marker. The researchers note that the increased risk of cardiac death associated with ERP is of a similar size to that associated with some other ECG abnormalities. However, although it might be worth paying special attention to young people with an inferior localization of ERP, finding ERP in a person without symptoms and without a family history of sudden cardiac death should not lead to further investigations or any preventative therapy, they suggest, because the absolute risk of cardiac arrest in such people is very low.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000314.
The US National Heart Lung and Blood Institute provides information on cardiovascular conditions, including sudden cardiac arrest and on arrhythmias
The American Heart Association also information on sudden cardiac death and on arrhythmias
The German Cardiac Society (Deutsche Gesellschaft fr Kardiologie) and the German Heart Foundation (Deutsche Herzstiftung) provide further information (in German) on cardiovascular conditions
The Heart Rhythm Foundation provides information on all aspects of heart arrhythmia
The Fondation Leducq Alliance Against Sudden Cardiac Death provides information on sudden cardiac arrest
MedlinePlus provides links to other resources about cardiac arrest and arrhythmias (in English and Spanish)
The MedlinePlus Encyclopedia has a page on electrocardiograms (in English and Spanish)
The Nobel Foundation provides an interactive electrocardiogram game
More information about the MONICA project and the KORA Study or is available