Nonalcoholic Fatty Liver Disease Is Associated With QT Prolongation in the General Population

Abstract

BackgroundNonalcoholic fatty liver disease (NAFLD) is independently associated with QT prolongation among patients with diabetes. It has not yet been determined whether this association remains valid in the general population. We designed an observational study to explore this association.Methods and ResultsWe conducted a cross-sectional analysis of 31 116 consecutive participants in our health management program. Heart rate–corrected QT (QTc) interval was derived from 12-lead electrocardiography and by Bazett’s formula. NAFLD was diagnosed by abdominal ultrasonography and classified as none, mild, moderate, or severe, according to the ultrasonographic criteria. A multivariable linear regression model was fitted for the association between QTc interval and potential predictors (including demographic, anthropometric, biochemical factors, and comorbidities). Multivariable logistic regression analyses were fitted to assess the association between the severity of NAFLD and QTc prolongation, with the adjustment of significant predictors derived from multivariable linear regression. The mean QTc interval was 421.3 ms (SD 45.4 ms). In the multivariable linear regression analyses, mild, moderate, and severe NAFLD were associated with increases of 2.55, 6.59, and 12.13 ms, respectively, in QTc interval compared with no NAFLD (all P<0.001). In the multivariable logistic regression analyses, mild, moderate, and severe NAFLD were associated with an increased risk for QTc prolongation, with odds ratios of 1.11 (95% CI: 1.01 to 1.21, P<0.05), 1.61 (95% CI: 1.36 to 1.9, P<0.001), and 1.31 (95% CI: 1.16 to 2.24, P<0.01), respectively, in women, and 1.11 (95% CI: 1.01 to 1.21, P<0.05), 1.39 (95% CI: 1.22 to 1.59, P<0.001), and 1.87 (95% CI: 1.16 to 2.24, P<0.001), respectively, in men, after adjusting for predictors known to be associated with the QTc interval. The association remained significant among subgroups with or without diabetes.ConclusionsThe severity of NAFLD was associated with a higher risk for QTc prolongation in the general population with and without diabetes.

Nonalcoholic Fatty Liver Disease Is Associated With Ventricular Arrhythmias in Patients With Type 2 Diabetes Referred for Clinically Indicated 24-Hour Holter Monitoring

“…However, it is important to emphasize that the association between NAFLD and ventricular arrhythmias remained significant in our study even after adjusting for many cardiometabolic risk factors, LV ejection fraction, preexisting IHD, and comorbid conditions. This finding corroborates previous observations reporting a strong association between NAFLD and an increased risk of QTc interval prolongation, which is a powerful risk factor for ventricular arrhythmias (8,9). In particular, we recently demonstrated that NAFLD was associated with an increased QTc interval among patients with type 2 diabetes without known liver diseases, and this association remained significant after adjusting for age, sex, hypertension, diabetes-related variables, LV hypertrophy, and comorbid conditions (8).…”

“…In particular, we recently demonstrated that NAFLD was associated with an increased QTc interval among patients with type 2 diabetes without known liver diseases, and this association remained significant after adjusting for age, sex, hypertension, diabetes-related variables, LV hypertrophy, and comorbid conditions (8). Similarly, Hung et al (9) reported that the ultrasonographic severity of NAFLD was associated with a higher risk for QTc interval prolongation in a large populationbased study, independently of age, sex, hypertension, diabetes, total cholesterol, eGFR, BMI, LV hypertrophy, history of IHD, or hypokalemia.…”

“…Preliminary evidence has suggested that NAFLD is associated with an increased prevalence of heart rate-corrected QT interval prolongation (i.e., an established risk factor for ventricular arrhythmias), independent of many cardiometabolic risk factors, both in patients with and without diabetes (8,9).…”

Pathogenesis of Insulin Resistance and Atherogenic Dyslipidemia in Nonalcoholic Fatty Liver Disease

“…This increased epicardial adipose tissue is associated with sympathovagal imbalances that can predispose to cardiac arrhythmias, such as first degree heart block prolongation and atrial fibrillation. [106][107][108][109][110][111] A prospective cohort study following diabetic patients for 10 years showed that patients with NAFLD developed atrial fibrillation more often than the controls. 112 These findings suggest a potential role for screening and surveillance of atherogenic dyslipidemia in patients with NAFLD.…”

Nonalcoholic Fatty Liver Disease (NAFLD) and Risk of Cardiac Arrhythmias: A New Aspect of the Liver-heart Axis

“…In a recent study, Hung et al 27 investigated whether the association between NAFLD and QTc interval prolongation also exists in the general adult population. In that study, the investigators reported that the severity of NAFLD was associated with a higher risk of QTc interval prolongation, even after adjustment for several cardiometabolic risk factors and other important comorbidities 27. Notably, such association was found to be present in all subgroups of patients analyzed, including patients with T2DM 27…”