Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank

Figures

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  FIGURE 1. Increasing adiposity is associated with increased QTc interval, after adjusting for sociodemographic, co-morbidity, and lifestyle factors. The change in QTc per unit and per standard deviation (SD) increment of in adiposity [quantified by BMI, body mass index (kg/m2); BF, body fat (%); WHR, waist:hip ratio (unit); HG, hip girth (cm); and WG, waist girth (cm)] are shown for the pooled cohort (A) and stratified by sex (B,C). Model 1 adjusted for sociodemographic factors; model 2 adjusted for lifestyle and comorbidities. All results presented reached significance p < 0.001. Results for QTc change per unit increment in WHR is provided in the main text.

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  FIGURE 2. Polygenic risk score (PRS) for genetically determined QT interval does not modulate the association between increasing adiposity and QTc interval. The change in QTc per unit (A) and per standard deviation (SD) (B) increment in adiposity [quantified by BMI, body mass index (kg/m2); BF, body fat (%); WHR, waist:hip ratio (unit); HG, hip girth (cm); WG, waist girth (cm)] are shown stratified by sex. Model 3 is adjusted for PRS in addition to sociodemographic and lifestyle factors and comorbidities as in model 2 (Figure 1). All results presented for model 3 in (A,B) reached significance p < 0.001. (C) There was no significant interaction between PRS and the adiposity:QTc relationships (P-interaction, PRS with adiposity:QTc) in either sex, suggesting genetics do not modulate the relationship between adiposity and QTc.

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  FIGURE 3. The QTc interval prolongs comparably with increasing adiposity in men and women stratified by PRS. The change in the QTc per unit and per SD increment of adiposity [quantified by BMI, body mass index (kg/m2); HG, hip girth (cm); WG, waist girth (cm); WHR, waist; hip ratio (unit)] is shown stratified according to low (<25%), intermediate (25–75%), and high (>75%) PRS, representing high, intermediate, and low repolarisation reserve, respectively for men (A) and women (B). All associations between QTc and adiposity measures reached statistical significance with p < 0.001.

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  FIGURE 4. Obesity and metabolic perturbation are independently associated with longer QTc interval and their effects are additive when they co-exist. Differences in the QTc interval (ΔQTc) referenced to the non-obese metabolically healthy (Ob-MU-) group for each clinical phenotype, in pooled (A) and sex-stratified (B,C) analysis. The p-values for the interactions between PRS and phenotype:QTc are shown in the in-set table (D) Ob, obese; MU, metabolically unhealthy; +, presence; –, absence; CI, confidence interval; PRS, polygenic risk score.