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Published in: Clinical Research in Cardiology 9/2015

01-09-2015 | Original Paper

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

Authors: Wesley T. O’Neal, Jimmy T. Efird, Hooman Kamel, Saman Nazarian, Alvaro Alonso, Susan R. Heckbert, W. T. Longstreth Jr., Elsayed Z. Soliman

Published in: Clinical Research in Cardiology | Issue 9/2015

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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.
Literature
1.
go back to reference 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):1562–1568PubMedCentralCrossRefPubMed 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):1562–1568PubMedCentralCrossRefPubMed
2.
go back to reference 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):2557–2564CrossRefPubMed 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):2557–2564CrossRefPubMed
3.
go back to reference 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):1460–1467PubMedCentralCrossRefPubMed 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):1460–1467PubMedCentralCrossRefPubMed
4.
go back to reference 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):2187–2194CrossRefPubMed 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):2187–2194CrossRefPubMed
5.
go back to reference 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):916–921CrossRefPubMed 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):916–921CrossRefPubMed
6.
go back to reference 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):704–709PubMedCentralCrossRefPubMed 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):704–709PubMedCentralCrossRefPubMed
7.
go back to reference Wolf PA, Abbott RD, Kannel WB (1991) Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 22(8):983–988CrossRefPubMed Wolf PA, Abbott RD, Kannel WB (1991) Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 22(8):983–988CrossRefPubMed
8.
go back to reference 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):2950–2953PubMedCentralCrossRefPubMed 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):2950–2953PubMedCentralCrossRefPubMed
9.
go back to reference 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):229–234CrossRefPubMed 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):229–234CrossRefPubMed
10.
go back to reference 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):871–881CrossRefPubMed 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):871–881CrossRefPubMed
11.
go back to reference 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):82–87CrossRefPubMed 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):82–87CrossRefPubMed
12.
go back to reference 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):982–991CrossRefPubMed 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):982–991CrossRefPubMed
13.
go back to reference 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):400–406PubMedCentralCrossRefPubMed 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):400–406PubMedCentralCrossRefPubMed
14.
go back to reference Gray RJ, Tsiatis AA (1989) A linear rank test for use when the main interest is in differences in cure rates. Biometrics 45(3):899–904CrossRefPubMed Gray RJ, Tsiatis AA (1989) A linear rank test for use when the main interest is in differences in cure rates. Biometrics 45(3):899–904CrossRefPubMed
15.
go back to reference 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):1817–1828PubMedCentralCrossRefPubMed 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):1817–1828PubMedCentralCrossRefPubMed
16.
go back to reference Lin DY, Fleming TR, De Gruttola V (1997) Estimating the proportion of treatment effect explained by a surrogate marker. Stat Med 16(13):1515–1527CrossRefPubMed Lin DY, Fleming TR, De Gruttola V (1997) Estimating the proportion of treatment effect explained by a surrogate marker. Stat Med 16(13):1515–1527CrossRefPubMed
17.
go back to reference 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):511–517CrossRefPubMed 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):511–517CrossRefPubMed
18.
go back to reference 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):2467–2477CrossRefPubMed 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):2467–2477CrossRefPubMed
19.
go back to reference 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):3357–3364CrossRefPubMed 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):3357–3364CrossRefPubMed
20.
go back to reference Cole SR, Hernan MA (2002) Fallibility in estimating direct effects. Int J Epidemiol 31(1):163–165CrossRefPubMed Cole SR, Hernan MA (2002) Fallibility in estimating direct effects. Int J Epidemiol 31(1):163–165CrossRefPubMed
Metadata
Title
The association of the QT interval with atrial fibrillation and stroke: the Multi-Ethnic Study of Atherosclerosis
Authors
Wesley T. O’Neal
Jimmy T. Efird
Hooman Kamel
Saman Nazarian
Alvaro Alonso
Susan R. Heckbert
W. T. Longstreth Jr.
Elsayed Z. Soliman
Publication date
01-09-2015
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology / Issue 9/2015
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-015-0838-z

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