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The separate and joint effects of prolonged QT interval and heart rate on mortality

  • Nan Hee Kim
    Correspondence
    Corresponding author at: Korea University Ansan Hospital, Gojan 1-dong, Danwon-gu, Gyunggi-do, Ansan 425-707, Republic of Korea. Tel.: +82 31 412 5952; fax: +82 31 412 6770.
    Affiliations
    Endocrinology and Metabolism, Korea University Medical School, Seoul, Republic of Korea
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  • Meda E. Pavkov
    Affiliations
    Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
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  • Robert G. Nelson
    Affiliations
    Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
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  • Robert L. Hanson
    Affiliations
    Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
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  • Peter H. Bennett
    Affiliations
    Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
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  • Jeffrey M. Curtis
    Affiliations
    Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
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  • Maurice L. Sievers
    Affiliations
    Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
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  • William C. Knowler
    Affiliations
    Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
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      Abstract

      Objectives

      Understanding why prolonged Bazett-corrected QT interval (QTc) is a risk factor for mortality is difficult, because QTc is positively correlated with heart rate. To optimally distinguish the effects of QT interval and heart rate on mortality, QT interval and heart rate were modeled separately and jointly in Pima Indians.

      Methods

      The effects of QT and heart rate on all-cause and cause-specific mortality were assessed in the overall study population and according to the presence or absence of diabetes using multivariable time-dependent proportional hazards models.

      Results

      Among 1488 nondiabetic and 990 diabetic subjects ≥25 years old, 81 nondiabetic and 149 diabetic subjects died during a median follow-up of 7.3 years. When included in the same regression model, QT and heart rate each predicted all-cause mortality [hazard ratios per standard deviation (SD) (95% confidence interval) = 1.31 (1.10–1.57) and 1.57 (1.32–1.87) respectively]. In nondiabetic subjects, hazard ratios for all-cause mortality were 1.54 (1.19–1.99) for QT and 1.86 (1.46–2.37) for heart rate. In diabetic subjects, hazard ratios for all-cause mortality were lower, 1.27 (1.00–1.62) for QT and 1.41 (1.12–1.78) for heart rate. In the overall study population, neither QT nor heart rate significantly predicted cardiovascular disease (CVD) mortality [hazard ratios = 1.13 (0.77–1.64) and 1.46 (0.98–2.19)] when adjusted for each other. Heart rate unadjusted for QT, however, predicted CVD mortality [hazard ratio = 1.34 (1.00–1.79)] in a separate model.

      Conclusions

      QT prolongation and high heart rate both predict all-cause mortality in Pima Indians, but heart rate was consistently the stronger predictor of the two.

      Abbreviations:

      ACR (albumin-to-creatinine ratio), ALD (alcoholic liver disease), CVD (cardiovascular disease), FPG (fasting plasma glucose), 2hPG (2h plasma glucose after a 75-g oral glucose load), HDL-C (HDL cholesterol), ICD-9 (International Classification of Disease, Ninth Revision), QT (measured QT interval), QTc (Bazett-corrected QT)

      Keywords

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