QT Interval and Long-Term Mortality Risk in the Framingham Heart Study

Authors

  • Peter A. Noseworthy M.D.,

    1. Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA
    2. The Program in Medical and Population Genetics, Broad Institute, Cambridge, MA
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  • Gina M. Peloso Ph.D.,

    1. Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA
    2. The National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA
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  • Shih-Jen Hwang Ph.D.,

    1. The National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA
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  • Martin G. Larson S.D.,

    1. The National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA
    2. The Department of Mathematics and Statistics, Boston University, Boston, MA
    3. The Department of Biostatistics, Boston University School of Public Health, Boston, MA
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  • Daniel Levy M.D.,

    1. The National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA
    2. The Center for Population Studies, National Heart, Lung and Blood Institute, Bethesda, MD
    3. The Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD
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  • Christopher J. O’Donnell M.D., M.P.H.,

    1. The National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA
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  • Christopher Newton-Cheh M.D., M.P.H.

    1. Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA
    2. The Program in Medical and Population Genetics, Broad Institute, Cambridge, MA
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  • This work was supported by the Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology (P.A.N.), the NIH/NHLBI (HL080025, HL098283 C.N.-C.), the Doris Duke Charitable Foundation (C.N.-C.), and the Burroughs Wellcome Fund (C.N.-C.). The FHS was supported by the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine (Contract No. N01-HC-25195).

  • The authors report no relationships with industry relevant to this work. Dr. Newton-Cheh is on a Merck scientific advisory board.

Christopher Newton-Cheh, M.D., M.P.H., Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge St, CPZN 5.242, Boston, MA 02114. Fax: 617-726-4105; E-mail: cnewtoncheh@chgr.mgh.harvard.edu

Abstract

Background: The association between QT interval and mortality has been demonstrated in large, prospective population-based studies, but the strength of the association varies considerably based on the method of heart rate correction. We examined the QT-mortality relationship in the Framingham Heart Study (FHS).

Methods: Participants in the first (original cohort, n = 2,365) and second generation (offspring cohort, n = 4,530) cohorts were included in this study with a mean follow up of 27.5 years. QT interval measurements were obtained manually using a reproducible digital caliper technique.

Results: Using Cox proportional hazards regression adjusting for age and sex, a 20 millisecond increase in QTc (using Bazett's correction; QT/RR1/2 interval) was associated with a modest increase in risk of all-cause mortality (HR 1.14, 95% CI 1.10–1.18, P < 0.0001), coronary heart disease (CHD) mortality (HR 1.15, 95% CI 1.05–1.26, P = 0.003), and sudden cardiac death (SCD, HR 1.19, 95% CI 1.03–1.37, P = 0.02). However, adjustment for heart rate using RR interval in linear regression attenuated this association. The association of QT interval with all-cause mortality persisted after adjustment for cardiovascular risk factors, but associations with CHD mortality and SCD were no longer significant.

Conclusion: In FHS, there is evidence of a graded relation between QTc and all-cause mortality, CHD death, and SCD; however, this association is attenuated by adjustment for RR interval. These data confirm that using Bazett's heart rate correction, QTc, overestimates the association with mortality. An association with all-cause mortality persists despite a more complete adjustment for heart rate and known cardiovascular risk factors.

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