Objective:
Prolongation of corrected QT interval (QTc) is associated with increased morbidity and mortality, but the association between the number of QT interval prolonging medications (QTPMs) versus selected non-pharmacologic risk factors on the magnitude of QTc lengthening is unknown. We examined these associations in a longitudinal study of a population-based cohort.
Methods:
We included 15,792 ARIC participants with a resting, standard 12-lead electrocardiogram and ≥ 1 measure of QTc over up to four triennial examinations between 1987 and 1998 (54,638 person-visits). Participants with QRS > 120 ms were excluded (n=2,333). To optimize clinical applicability, QTc was calculated using Bazett’s equation. At each visit, we identified participants using ≥ 1 AzCERT-classified QTPMs, age > 65 years, females, and those with left ventricular hypertrophy (LVH), or QTc > 500 ms at the prior visit. We used linear regression for 36,513 person-visit observations from visits 2-4 to examine QTc lengthening associations. Visit indicators were controlled for time, and standard errors were corrected for repeat observations per person.
Results:
Use of any QTPM increased from 9% to 17% between visits 1 and 4 and occurred more frequently among females and participants with LVH. Among person-visit observations from Visit 2-4, 70% (n=25,513) had at least one risk factor including age > 65 years (25%), female sex (56%), LVH (8%) and QTc>500 ms (1%). In patients receiving no QTPM, female sex was associated with the greatest QTc lengthening at 13 ms [95% CI 12-13] followed by LVH at 7 ms [6-9], QTc > 500 ms at 7 [4-10], and age > 65 at 2 ms [1-3]. Mean QTc increased with increasing number of QTPMs and risk factors (Table). The greatest QTc lengthening occurred in participants using ≥ 2 medications with ≥ 1 risk factor.
Conclusions:
Risk factors, particularly female sex, contribute more to QTc lengthening than QTPMs.
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