Elsevier

Journal of Electrocardiology

Volume 41, Issue 6, November–December 2008, Pages 704-710
Journal of Electrocardiology

Length of the QT interval: determinants and prognostic implications in a population-based prospective study of older men

https://doi.org/10.1016/j.jelectrocard.2008.01.010Get rights and content

Abstract

Objective

We examined potential determinants and prognostic value of the corrected QT interval (QTc).

Design

A total of 4252 British men aged 60 to 79 years had a resting 12-lead electrocardiogram. Potential determinants of the QTc were assessed using multivariable regression. Men were followed up for 7 years.

Results

A 1 standard deviation increase in QTc (26 milliseconds) was associated with increased all-cause mortality (hazard ratio, 1.13; 95% confidence interval, 1.05-1.22). Longer QTc was associated with increasing age, preexisting coronary heart disease, and a range of drugs. Shorter QTc was present in diabetics and smokers. Corrected QT interval was related inversely with serum potassium and calcium and positively with serum urate, sodium, and systolic blood pressure. The relation of QTc to all-cause mortality was independent of adjustment for these factors.

Conclusions

Age, preexisting coronary heart disease, certain medications and biochemical factors, and diabetes are independently associated with QTc. Corrected QT interval is an independent predictor of all-cause mortality.

Introduction

The QT interval corrected for heart rate (QTc) measures the time from the start of ventricular depolarization to the completion of repolarization. In the clinical context, longer QTc intervals are implicated in the generation of ventricular arrhythmias such as torsades de pointes, which can degenerate to fatal ventricular fibrillation. Long QT syndrome has been conceptualized as 2 groups: inherited and acquired. Our understanding of the inherited type has developed considerably, but relatively less is known about acquired QTc lengthening.1 A number of population-based cohort studies have investigated the prognostic importance of long QTc in adults with varying results.2, 3, 4, 5, 6, 7, 8 Many have shown a tendency toward increased mortality with longer QTc intervals, particularly above a cutoff value of 440 milliseconds.2, 6, 7, 9 It is likely that in an older population, much of this QTc lengthening is acquired, but little is known about the determinants of QTc in the general population.

There are many factors that may lengthen the QTc. Biochemical abnormalities including hypokalemia, hypomagnesemia, and hypocalcemia are implicated.10 Although there are large studies to show hypokalemia might lengthen the QTc,11, 12 there is much less information on hypomagnesemia and hypocalcemia. Drugs, including some antiarrhythmic medications and noncardiac drugs ranging from psychiatric medications to certain antibiotics, may lengthen the QTc interval.13 Intracranial injury has been implicated in QTc lengthening, and there has been some interest in the development of long QTc in people with liver cirrhosis and patient's with end-stage renal disease.14, 11, 15

There is little evidence on the importance of such determinants of the QTc in the general population and how they affect its prognostic value. We have therefore explored the determinants of lengthening QTc interval at the population level in a cohort of older men. Potential determinants examined include a range of biochemical factors, medications, as well as established cardiovascular risk factors including diabetes, cigarette smoking, and hypertension. Phenomena that lengthen the QRS complex inevitably lead to a longer QTc, so to look at the effect of QTc purely, these have been excluded. We have also examined the prognostic value of QTc interval and used multivariable survival analyses to adjust for these determinants to ascertain if the QTc interval is an independent predictor of prognosis.

Section snippets

Study population

The British Regional Heart Study is a prospective cohort study investigating cardiovascular risk. Between 1978 and 1980, 7735 men aged 40 to 59 years were selected from 24 medium-sized British towns using age-sex registers from one general practice in each town. Between 1998 and 2000, all the surviving men were recalled for a 20-year reexamination, and 4252 men attended (77% response rate). The examination included physical measurements, resting 12-lead electrocardiograms (ECGs) and blood

Results

Follow-up data were available on the entire cohort. Corrected QT interval data were available for 4231 of the 4252 men, of whom 295 were excluded for having abnormalities prolonging the QRS interval, as defined in the methods. A further 361 participants did not have complete biochemical data, leaving complete data for analysis on 3596 participants. All the variables in Table 1, Table 2 were used as adjustors in the multivariable regression and multivariable proportional hazards regression. The

Discussion

This study shows that a long QTc is an independent prognostic indicator of all-cause mortality and establishes determinants of the QTc at a population level. It suggests previously undocumented associations, particularly with serum urate concentrations, and casts doubt on others such as with hypomagnesaemia.

When ECGs were performed on this cohort at the beginning of this study 20 years before the data analyzed here, less than 1% of the cohort had a long QTc.25 This suggests that most of the QTc

Acknowledgments

Biochemical analyses were carried out in the Department of Chemical Pathology, Royal Free Hospital (Dr M. Thomas).

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  • Cited by (0)

    The British Regional Heart Study is supported by the British Heart Foundation and receives support from the Department of Health. S.M.A. Sohaib was funded through the North Central Thames Foundation School Academic Foundation Programme at University College London.

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