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Comparative Study
. 2012 Apr 17;59(16):1460-7.
doi: 10.1016/j.jacc.2012.01.025.

Prolongation of QTc and risk of stroke: The REGARDS (REasons for Geographic and Racial Differences in Stroke) study

Elsayed Z Soliman  1 , George Howard, Mary Cushman, Brett Kissela, Dawn Kleindorfer, Anh Le, Suzanne Judd, Leslie A McClure, Virginia J Howard
Affiliations
Comparative Study

Prolongation of QTc and risk of stroke: The REGARDS (REasons for Geographic and Racial Differences in Stroke) study

Elsayed Z Soliman et al. J Am Coll Cardiol. .

Abstract

Objectives: The purpose of this study was to examine the association between prolongation of QT interval corrected for heart rate (QTc) with incident stroke.

Background: Unlike cardiovascular morbidity and mortality, little is known about the relationship between QTc and risk of stroke.

Methods: A total of 27,411 participants age 45 years and older without previous stroke from the REGARDS (REasons for Geographic and Racial Differences in Stroke) study were included in this analysis. QTc was calculated using Framingham formula (QTc(Fram)). Stroke cases were identified and adjudicated during up to 8.2 years of follow-up (median, 5.1 years).

Results: The risk of incident stroke in study participants with prolonged QTc(Fram) was almost 3 times the risk in those with normal QTc(Fram) (hazard ratio [HR] [95% confidence interval (CI)]: 2.88 [2.12 to 3.92], p < 0.0001). After adjustment for demographics (age, race, and sex), traditional stroke risk factors (antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, and previous cardiovascular disease), warfarin use, aspirin use, QRS duration and use of QTc-prolonging drugs, the risk of stroke remained significantly high (HR [95% CI]: 1.67 [1.16 to 2.41], p = 0.0061) and was consistent across several subgroups of REGARDS study participants. Similar results were obtained when the risk of stroke was estimated per 1-SD increase in QTc(Fram), (HR [95% CI]: 1.12 [1.03 to 1.21], p = 0.0053 in multivariable-adjusted model) and when other QTc correction formulas including those of Hodge, Bazett, and Fridericia were used.

Conclusions: QTc prolongation is associated with a significantly increased risk of incident stroke independent of traditional stroke risk factors. Examining the risk of stroke associated with QTc-prolonging drugs may be warranted.

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Figures

Figure 1
Figure 1
Kaplan Meir curves for incident stroke in REGARDS participants with and without prolonged QTcFram. *The horizontal axis shows follow-up time in years, and the vertical axis the proportion of the population stroke-free for those without (red line) and with (blue line) prolonged QTc.
Figure 2
Figure 2
Prolongation of QTcFram and risk of incident stroke within subgroups of REGARDS study participants *Hazard ratios are adjusted for demographics (age, race, sex), traditional stroke risk factors (antihypertensive medication use, systolic blood pressure, smoking status, diabetes, left ventricular hypertrophy, atrial fibrillation, prior cardiovascular disease), warfarin use, QRS duration and use of QT-prolonging drugs †LVH, left ventricular hypertrophy; Atrial Fib, atrial fibrillation; CVD, prior cardiovascular disease ‡ Black circles in the graph represent the HR and lines represent the 95% CI § No significant interaction between the categories within each subgroups were observed.
See this image and copyright information in PMC

References

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