Relation of total bilirubin and QT interval prolongation (from the Third National Health and Nutrition Examination Survey)

Abstract Objective The association of bilirubin with cardiovascular disease (CVD) is controversial. We sought to explore the association of total bilirubin (TB) levels with QT interval in a multiracial cohort. Methods A total of 6,627 participants (59.0 ± 13.3 years; 52.6% women, 49.7% Non‐Hispanic Whites) without CVD from the Third National Health and Nutrition Examination Survey were included in this analysis. QT was automatically measured from digital 12‐lead electrocardiogram in a central reading center. A multivariable logistic regression model was used to examine the cross‐sectional association between tertiles of TB and prolonged QT interval (≥450 ms in men and ≥460 ms in women). Results The prevalence of prolonged QT was higher among those with higher levels of TB (prolonged QT prevalence was 4.7%, 6.8%, and 7.0% across TB lower (0–0.4 mg/dl), middle (0.5–1.6 mg/dl), and higher (0.70–4.30 mg/dl) tertiles, respectively). In a model adjusted for potential confounders, participants within the highest TB tertile had significantly greater odds of the prolonged QT interval (Odds ratios [95% confidence interval] 1.53 [1.16–2.02]) compared to those with bilirubin levels in the first tertile. Each 0.29 mg/dl increase in TB levels was associated with a 12% ( p ‐value <.0001) increase in the prevalence of prolonged QT interval. This association was stronger in men than in women (interaction p ‐value = .04). Conclusion Elevated bilirubin levels are associated with a prolonged QT interval. This finding extends our current knowledge on the relationship between serum bilirubin and CVD by demonstrating a link between higher TB and abnormal cardiac repolarization.