University of Oulu

Arttu Holkeri, Antti Eranti, M. Anette Haukilahti, Tuomas Kerola, Tuomas V. Kenttä, Kai Noponen, Tapio Seppänen, Harri Rissanen, Markku Heliövaara, Paul Knekt, M. Juhani Junttila, Heikki V. Huikuri, Aapo L. Aro, Prevalence and Prognostic Significance of Negative U-waves in a 12-lead electrocardiogram in the General Population, The American Journal of Cardiology, Volume 123, Issue 2, 2019, Pages 267-273, ISSN 0002-9149,

Prevalence and prognostic significance of negative U-waves in a 12-lead electrocardiogram in the general population

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Author: Holkeri, Arttu1; Eranti, Antti2; Haukilahti, M. Anette3;
Organizations: 1Division of Cardiology, Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland
2Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland
3Research Unit of Internal Medicine, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland
4Center for Machine Vision and Signal Analysis, University of Oulu, Oulu, Finland
5National Institute for Health and Welfare, Helsinki, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.3 MB)
Persistent link:
Language: English
Published: Elsevier, 2019
Publish Date: 2019-10-19


Negative U-waves are a relatively rare finding in an electrocardiogram (ECG), but are often associated with cardiac disease. The prognostic significance of negative U-waves in the general population is unknown. We evaluated 12-lead ECGs of 6,518 adults (45% male, mean age 50.9 ± 13.8 years) for the presence of U-waves, and followed the subjects for 24.5 ± 10.3 years. Primary end points were all-cause mortality, cardiac mortality, and sudden cardiac death; secondary end point was hospitalization due to cardiac causes. Negative U-waves (amplitude ≥0.05 mV) were present in 231 subjects (3.5%), minor negative (amplitude <0.05 mV) or discordant U-waves in 1,004 subjects (15.4%), normal positive U-waves in 3,950 (60.6%) subjects, and no U-waves were observed in 603 subjects (9.3%). In 730 subjects (11.2%), U-waves were unassessable. When adjusted for age and gender, negative U-waves were associated with all end points (p <0.01). In an analysis adjusted for multiple demographic and clinical factors, in men, negative U-waves were associated with increased risk of all-cause mortality (hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.26 to 2.03; p <0.001), cardiac mortality (HR 1.74; 95% CI 1.26 to 2.39; p = 0.001), and cardiac hospitalization (HR 1.67; 95% CI 1.27 to 2.18; p <0.001), but not with sudden cardiac death, whereas women did not show a significant association to any of the end points (p >0.30). In conclusion, negative U-waves are associated with adverse events in the general population. In men, this association is independent of cardiovascular risk factors.

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Series: The American journal of cardiology
ISSN: 0002-9149
ISSN-E: 1879-1913
ISSN-L: 0002-9149
Volume: 123
Issue: 2
Pages: 267 - 273
DOI: 10.1016/j.amjcard.2018.10.010
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: We thank the National Institute for Health and Welfare for their important contribution.
Copyright information: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license