Skip to main content

The association of the QT interval with atrial fibrillation and stroke: the Multi-Ethnic Study of Atherosclerosis

Abstract

Background

Prolongation of the QT interval is associated with an increased risk of atrial fibri llation (AF) and stroke.

Objectives

The purpose of this analysis was to determine if AF explains the association between prolonged QT and stroke.

Methods

A total of 6305 participants (mean age 62 ± 10 years; 54 % women; 38 % whites; 27 % blacks; 23 % Hispanics; 12 % Chinese–Americans) from the Multi-Ethnic Study of Atherosclerosis (MESA) were included in this analysis. A linear scale was used to compute heart rate-adjusted QT (QTa). Prolonged QTa was defined as ≥460 ms in women and ≥450 ms in men. Incident AF cases were identified using hospital discharge records and Medicare claims data. Vascular neurologists adjudicated stroke events by medical record review. Cox regression was used to examine the association between prolonged QTa and stroke with and without AF.

Results

A total of 216 (3.4 %) of study participants had prolonged QTa. Over a median follow-up of 8.5 years, 280 (4.4 %) participants developed AF and 128 (2.0 %) participants developed stroke. In a multivariable Cox regression analysis adjusted for socio-demographics, cardiovascular risk factors, and potential confounders, prolonged QTa was associated with an increased risk of AF (HR = 1.7, 95 % CI 1.1, 2.6) and stroke (HR = 2.3, 95 % CI 1.3, 4.1). When AF was included as a time-dependent covariate, the association between prolonged QTa and stroke was not substantively altered (HR = 2.4, 95 % CI 1.3, 4.3).

Conclusion

The increased risk of stroke in those with prolonged QT potentially is not explained by documented AF. Further research is needed to determine if subclinical AF explains the association between the QT interval and stroke.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. Mandyam MC, Soliman EZ, Alonso A, Dewland TA, Heckbert SR, Vittinghoff E, Cummings SR, Ellinor PT, Chaitman BR, Stocke K, Applegate WB, Arking DE, Butler J, Loehr LR, Magnani JW, Murphy RA, Satterfield S, Newman AB, Marcus GM (2013) The QT interval and risk of incident atrial fibrillation. Heart Rhythm 10(10):1562–1568

    PubMed Central  Article  PubMed  Google Scholar 

  2. Nielsen JB, Graff C, Pietersen A, Lind B, Struijk JJ, Olesen MS, Haunso S, Gerds TA, Svendsen JH, Kober L, Holst AG (2013) J-shaped association between QTc interval duration and the risk of atrial fibrillation: results from the Copenhagen ECG study. J Am Coll Cardiol 61(25):2557–2564

    Article  PubMed  Google Scholar 

  3. Soliman EZ, Howard G, Cushman M, Kissela B, Kleindorfer D, Le A, Judd S, McClure LA, Howard VJ (2012) Prolongation of QTc and risk of stroke: the REGARDS (REasons for Geographic and Racial Differences in Stroke) study. J Am Coll Cardiol 59(16):1460–1467

    PubMed Central  Article  PubMed  Google Scholar 

  4. Cardoso CR, Salles GF, Deccache W (2003) QTc interval prolongation is a predictor of future strokes in patients with type 2 diabetes mellitus. Stroke 34(9):2187–2194

    Article  PubMed  Google Scholar 

  5. Maebuchi D, Arima H, Doi Y, Ninomiya T, Yonemoto K, Tanizaki Y, Kubo M, Hata J, Matsumura K, Iida M, Kiyohara Y (2010) QT interval prolongation and the risks of stroke and coronary heart disease in a general Japanese population: the Hisayama study. Hypertens Res 33(9):916–921

    Article  PubMed  Google Scholar 

  6. Johnson JN, Tester DJ, Perry J, Salisbury BA, Reed CR, Ackerman MJ (2008) Prevalence of early-onset atrial fibrillation in congenital long QT syndrome. Heart Rhythm 5(5):704–709

    PubMed Central  Article  PubMed  Google Scholar 

  7. Wolf PA, Abbott RD, Kannel WB (1991) Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 22(8):983–988

    Article  CAS  PubMed  Google Scholar 

  8. Soliman EZ, Howard G, Meschia JF, Cushman M, Muntner P, Pullicino PM, McClure LA, Judd S, Howard VJ (2011) Self-reported atrial fibrillation and risk of stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Stroke 42(10):2950–2953

    PubMed Central  Article  PubMed  Google Scholar 

  9. Wolf PA, Mitchell JB, Baker CS, Kannel WB, D’Agostino RB (1998) Impact of atrial fibrillation on mortality, stroke, and medical costs. Arch Intern Med 158(3):229–234

    Article  CAS  PubMed  Google Scholar 

  10. Bild DE, Bluemke DA, Burke GL, Detrano R, Diez Roux AV, Folsom AR, Greenland P, Jacob DR Jr, Kronmal R, Liu K, Nelson JC, O’Leary D, Saad MF, Shea S, Szklo M, Tracy RP (2002) Multi-ethnic study of atherosclerosis: objectives and design. Am J Epidemiol 156(9):871–881

    Article  PubMed  Google Scholar 

  11. Devereux RB, Casale PN, Eisenberg RR, Miller DH, Kligfield P (1984) Electrocardiographic detection of left ventricular hypertrophy using echocardiographic determination of left ventricular mass as the reference standard. Comparison of standard criteria, computer diagnosis and physician interpretation. J Am Coll Cardiol 3(1):82–87

    Article  CAS  PubMed  Google Scholar 

  12. Rautaharju PM, Surawicz B, Gettes LS, Bailey JJ, Childers R, Deal BJ, Gorgels A, Hancock EW, Josephson M, Kligfield P, Kors JA, Macfarlane P, Mason JW, Mirvis DM, Okin P, Pahlm O, van Herpen G, Wagner GS, Wellens H, American Heart Association E, Arrhythmias Committee CoCC, American College of Cardiology F, Heart Rhythm Society (2009) AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part IV: the ST segment, T and U waves, and the QT interval: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol 53(11):982–991

    Article  PubMed  Google Scholar 

  13. Soliman EZ, Shah AJ, Boerkircher A, Li Y, Rautaharju PM (2014) Inter-relationship between electrocardiographic left ventricular hypertrophy and QT prolongation as predictors of increased risk of mortality in the general population. Circ Arrhythm Electrophysiol 7(3):400–406

    PubMed Central  Article  PubMed  Google Scholar 

  14. Gray RJ, Tsiatis AA (1989) A linear rank test for use when the main interest is in differences in cure rates. Biometrics 45(3):899–904

    Article  CAS  PubMed  Google Scholar 

  15. Jun HJ, Austin SB, Wylie SA, Corliss HL, Jackson B, Spiegelman D, Pazaris MJ, Wright RJ (2010) The mediating effect of childhood abuse in sexual orientation disparities in tobacco and alcohol use during adolescence: results from the Nurses’ Health Study II. Cancer Causes Control 21(11):1817–1828

    PubMed Central  Article  PubMed  Google Scholar 

  16. Lin DY, Fleming TR, De Gruttola V (1997) Estimating the proportion of treatment effect explained by a surrogate marker. Stat Med 16(13):1515–1527

    Article  CAS  PubMed  Google Scholar 

  17. Marrie RA, Dawson NV, Garland A (2009) Quantile regression and restricted cubic splines are useful for exploring relationships between continuous variables. J Clin Epidemiol 62(5):511–517

    Article  PubMed  Google Scholar 

  18. Gladstone DJ, Spring M, Dorian P, Panzov V, Thorpe KE, Hall J, Vaid H, O’Donnell M, Laupacis A, Cote R, Sharma M, Blakely JA, Shuaib A, Hachinski V, Coutts SB, Sahlas DJ, Teal P, Yip S, Spence JD, Buck B, Verreault S, Casaubon LK, Penn A, Selchen D, Jin A, Howse D, Mehdiratta M, Boyle K, Aviv R, Kapral MK, Mamdani M, EMBRACE Investigators and Coordinators (2014) Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med 370(26):2467–2477

    Article  CAS  PubMed  Google Scholar 

  19. Grond M, Jauss M, Hamann G, Stark E, Veltkamp R, Nabavi D, Horn M, Weimar C, Kohrmann M, Wachter R, Rosin L, Kirchhof P (2013) Improved detection of silent atrial fibrillation using 72-hour Holter ECG in patients with ischemic stroke: a prospective multicenter cohort study. Stroke 44(12):3357–3364

    Article  PubMed  Google Scholar 

  20. Cole SR, Hernan MA (2002) Fallibility in estimating direct effects. Int J Epidemiol 31(1):163–165

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute and by grants UL1-RR-024156 and UL1-RR-025005 from NCRR.

Conflict of interest

Dr. Nazarian is a consultant and principal investigator for research funding awarded to Johns Hopkins University from Biosense Webster Inc.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wesley T. O’Neal.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

O’Neal, W.T., Efird, J.T., Kamel, H. et al. The association of the QT interval with atrial fibrillation and stroke: the Multi-Ethnic Study of Atherosclerosis. Clin Res Cardiol 104, 743–750 (2015). https://doi.org/10.1007/s00392-015-0838-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-015-0838-z

Keywords

  • Atrial fibrillation
  • Stroke
  • Long QT