QT-interval duration and mortality rate: results from the Third National Health and Nutrition Examination Survey

Abstract

Background: Extreme prolongation or reduction of the QT interval predisposes patients to malignant ventricular arrhythmias and sudden cardiac death, but the association of variations in the QT interval within a reference range with mortality end points in the general population is unclear.

Methods: We included 7828 men and women from the Third National Health and Nutrition Examination Survey. Baseline QT interval was measured via standard 12-lead electrocardiographic readings. Mortality end points were assessed through December 31, 2006 (2291 deaths).

Results: After an average follow-up of 13.7 years, the association between QT interval and mortality end points was U-shaped. The multivariate-adjusted hazard ratios comparing participants at or above the 95th percentile of age-, sex-, race-, and R-R interval-corrected QT interval (≥439 milliseconds) with participants in the middle quintile (401 to <410 milliseconds) were 2.03 (95% confidence interval, 1.46-2.81) for total mortality, 2.55 (1.59-4.09) for mortality due to cardiovascular disease (CVD), 1.63 (0.96-2.75) for mortality due to coronary heart disease, and 1.65 (1.16-2.35) for non-CVD mortality. The corresponding hazard ratios comparing participants with a corrected QT interval below the fifth percentile (<377 milliseconds) with those in the middle quintile were 1.39 (95% confidence interval, 1.02-1.88) for total mortality, 1.35 (0.77-2.36) for CVD mortality, 1.02 (0.44-2.38) for coronary heart disease mortality, and 1.42 (0.97-2.08) for non-CVD mortality. Increased mortality also was observed with less extreme deviations of QT-interval duration. Similar, albeit weaker, associations also were observed with Bazett-corrected QT intervals.

Conclusion: Shortened and prolonged QT-interval durations, even within a reference range, are associated with increased mortality risk in the general population.

Figure 1

Multivariate-adjusted hazard ratios (HRs) for total mortality rate and mortality due to cardiovascular disease (CVD), coronary heart disease (CHD), and non-CVD causes. Mortality end points were associated with age-, sex-, race-, and R-R interval–corrected QT interval (QTrras) and Bazett heart rate–corrected QT interval (QTb). Models were adjusted for age; race or ethnicity (non-Hispanic white, non-Hispanic black, Mexican American, or other); sex; R-R interval (restricted quadratic splines with knots at the 5th, 50th, and 95th percentiles); body mass index (calculated as weight in kilograms divided by height in meters squared); smoking status (current, former, or never); alcohol consumption (<12 or ≥12 drinks in the past year); high school education (<12 years or ≥12 years); annual household income (<$20 000 or ≥$20 000); levels of total and high-density lipoprotein cholesterol, serum potassium, and serum calcium; systolic blood pressure; use of blood pressure–lowering medication; diabetes mellitus; history of myocardial infarction; history of congestive heart failure; use of QT-prolonging medications; and use of β-blockers. Wald test P values for testing the association of QTrras categories with mortality end points were less than .001 for total mortality and CVD mortality, .02 for CHD mortality, and .008 for non-CVD mortality. The corresponding P values for QTb were .08, .24, .49, and .28, respectively. CI indicates confidence interval.

Figure 2

Multivariate-adjusted hazard ratios for total mortality rate and mortality due to cardiovascular disease (CVD), coronary heart disease (CHD), and non-CVD causes. Mortality end points were associated with age-, sex-, race-, and R-R interval–adjusted QT interval (QTrras) and Bazett heart rate–corrected QT interval (QTb) using restricted quadratic splines. The horizontal dotted line indicates a hazard ratio of 1. Adjustment factors are described in Figure 1.

Figure 3

Multivariate-adjusted hazard ratios of total mortality rate and mortality due to cardiovascular disease (CVD), coronary heart disease (CHD), and non-CVD causes. Mortality end points were associated with age-, sex-, race-, and R-R interval–adjusted QT interval (QTrras) using restricted quadratic splines, stratified by sex. The horizontal dotted line indicates a hazard ratio of 1. Adjustment factors are described in Figure 1. P values are for interaction.