Increasing adiposity and metabolic dysfunction prolong QTc interval and increase risk of ventricular arrhythmias: results from the UK Biobank

Abstract

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): National Institute for Health Research Background/purpose: Small-scale studies have associated obesity and metabolic ill-health with QTc interval prolongation. Whether these associations are modulated by an underlying genetic predilection and translate into higher risks of ventricular arrhythmias (VA) is unknown. Methods Using the UK Biobank and adjusted multivariate regression analysis, we studied the associations between QTc and clinical measures of adiposity and metabolic ill-health. A polygenic risk score was used to determine whether these associations are modulated by a genetic predilection for QTc prolongation. We compared QTc between four clinical phenotypes defined according to presence (+) or absence (-) of obesity (Ob), and metabolic ill-health (MU). Logistic regression was used to calculate odds ratios (OR) for VA amongst these groups. Results 23,683 individuals (11,563 male, mean age 61.0 + 7.5years) had ECG and clinical data available. QTc prolongs with increasing body mass index (0.76ms/kg/m2, 95%CI: 0.68-0.83ms/kg/m2), body fat (0.45ms/%, 95%CI:0.39-0.50ms/%), hip girth (0.35ms/cm, 95%CI:0.31-0.39ms/cm) and waist girth (0.32ms/cm, 95%CI:0.29-0.35ms/cm); all p < 0.001. Genetically determined repolarisation reserve has no significant modulatory effect on the QTc-prolonging effects of increasing adiposity. Referenced to Ob-MU-, Ob + MU- and Ob-MU+ independently prolong QTc to a comparable extent, and Ob + MU+ has an additive effect on QTc prolongation. With reference to Ob-MU-, OR for VA in Ob-MU+ males and females were 5.96 (95%CI:4.70-7.55) and 5.10 (95%CI:3.34-7.80), respectively. OR for Ob + MU+ were 6.99 (95%CI:5.72-8.54) and 3.56 (95%CI:2.66-4.77) in males and females, respectively, (all p < 0.001, see Table). Conclusion Adiposity and metabolic perturbation prolong QTc to a similar extent, and their co-existence exerts an additive effect. These effects are independent of genetically determined repolarisation reserve. Despite their comparable QTc prolonging effects, metabolic ill-health is associated with higher OR for VA than obesity. VA in obesity and metabolic dysfunctionReference phenotypeOb + MU-Ob-MU+Ob + MU+Ob-MU+male1.10(0.87-1.39)ns5.96 (4.70-7.55)***6.99(5.72-8.54)***female0.87(0.64-1.18)ns5.10(3.34-7.80)***3.56(2.66-4.77)***Ob + MU-male--6.01(4.98-7.26)***female--5.61(4.18-7.52)***Ob + MU+male--1.25(1.05-1.49)*female--1.16(0.80-1.68)nsOb, obese; MU, metabolically unhealthy; +, presence; -, absence; ns, non-significant; *p < 0.05; ***p < 0.001. Abstract Figure. QTc in obesity and metabolic dysfunction