Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank
BackgroundSmall-scale studies have linked obesity (Ob) and metabolic ill-health with proarrhythmic repolarisation abnormalities. Whether these are observed at a population scale, modulated by individuals’ genetics, and confer higher risks of ventricular arrhythmias (VA) are not known.Methods and Res...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.939156/full |
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| author | Kiran Haresh Kumar Patel Xinyang Li Xiao Xu Lin Sun Maddalena Ardissino Prakash P. Punjabi Sanjay Purkayastha Nicholas S. Peters James S. Ware Fu Siong Ng |
| author_facet | Kiran Haresh Kumar Patel Xinyang Li Xiao Xu Lin Sun Maddalena Ardissino Prakash P. Punjabi Sanjay Purkayastha Nicholas S. Peters James S. Ware Fu Siong Ng |
| author_sort | Kiran Haresh Kumar Patel |
| collection | DOAJ |
| description | BackgroundSmall-scale studies have linked obesity (Ob) and metabolic ill-health with proarrhythmic repolarisation abnormalities. Whether these are observed at a population scale, modulated by individuals’ genetics, and confer higher risks of ventricular arrhythmias (VA) are not known.Methods and ResultsFirstly, using the UK Biobank, the association between adiposity and QTc interval was assessed in participants with a resting 12-lead ECG (n = 23,683), and a polygenic risk score (PRS) was developed to investigate any modulatory effect of genetics. Participants were also categorised into four phenotypes according to the presence (+) or absence (–) of Ob, and if they were metabolically unhealthy (MU+) or not (MU-). QTc was positively associated with body mass index (BMI), body fat (BF), waist:hip ratio (WHR), and hip and waist girths. Individuals’ genetics had no significant modulatory effect on QTc-prolonging effects of increasing adiposity. QTc interval was comparably longer in those with metabolic perturbation without obesity (Ob-MU+) and obesity alone (Ob+MU-) compared with individuals with neither (Ob-MU-), and their co-existence (Ob+MU+) had an additive effect on QTc interval. Secondly, for 502,536 participants in the UK Biobank, odds ratios (ORs) for VA were computed for the four clinical phenotypes above using their past medical records. Referenced to Ob-MU-, ORs for VA in Ob-MU+ men and women were 5.96 (95% CI: 4.70–7.55) and 5.10 (95% CI: 3.34–7.80), respectively. ORs for Ob+MU+ were 6.99 (95% CI: 5.72–8.54) and 3.56 (95% CI: 2.66–4.77) in men and women, respectively.ConclusionAdiposity and metabolic perturbation increase QTc to a similar degree, and their co-existence exerts an additive effect. These effects are not modulated by individuals’ genetics. Metabolic ill-health is associated with a higher OR for VA than obesity. |
| first_indexed | 2024-12-12T17:15:05Z |
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| id | doaj.art-8596b433b8b4479bbd23d38357b5136c |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-12T17:15:05Z |
| publishDate | 2022-06-01 |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-8596b433b8b4479bbd23d38357b5136c2022-12-22T00:17:49ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-06-01910.3389/fcvm.2022.939156939156Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK BiobankKiran Haresh Kumar Patel0Xinyang Li1Xiao Xu2Lin Sun3Maddalena Ardissino4Prakash P. Punjabi5Sanjay Purkayastha6Nicholas S. Peters7James S. Ware8Fu Siong Ng9National Heart and Lung Institute, Imperial College London, London, United KingdomNational Heart and Lung Institute, Imperial College London, London, United KingdomNational Heart and Lung Institute, Imperial College London, London, United KingdomNational Heart and Lung Institute, Imperial College London, London, United KingdomNational Heart and Lung Institute, Imperial College London, London, United KingdomImperial College London, London, United KingdomImperial College London, London, United KingdomNational Heart and Lung Institute, Imperial College London, London, United KingdomNational Heart and Lung Institute, Imperial College London, London, United KingdomNational Heart and Lung Institute, Imperial College London, London, United KingdomBackgroundSmall-scale studies have linked obesity (Ob) and metabolic ill-health with proarrhythmic repolarisation abnormalities. Whether these are observed at a population scale, modulated by individuals’ genetics, and confer higher risks of ventricular arrhythmias (VA) are not known.Methods and ResultsFirstly, using the UK Biobank, the association between adiposity and QTc interval was assessed in participants with a resting 12-lead ECG (n = 23,683), and a polygenic risk score (PRS) was developed to investigate any modulatory effect of genetics. Participants were also categorised into four phenotypes according to the presence (+) or absence (–) of Ob, and if they were metabolically unhealthy (MU+) or not (MU-). QTc was positively associated with body mass index (BMI), body fat (BF), waist:hip ratio (WHR), and hip and waist girths. Individuals’ genetics had no significant modulatory effect on QTc-prolonging effects of increasing adiposity. QTc interval was comparably longer in those with metabolic perturbation without obesity (Ob-MU+) and obesity alone (Ob+MU-) compared with individuals with neither (Ob-MU-), and their co-existence (Ob+MU+) had an additive effect on QTc interval. Secondly, for 502,536 participants in the UK Biobank, odds ratios (ORs) for VA were computed for the four clinical phenotypes above using their past medical records. Referenced to Ob-MU-, ORs for VA in Ob-MU+ men and women were 5.96 (95% CI: 4.70–7.55) and 5.10 (95% CI: 3.34–7.80), respectively. ORs for Ob+MU+ were 6.99 (95% CI: 5.72–8.54) and 3.56 (95% CI: 2.66–4.77) in men and women, respectively.ConclusionAdiposity and metabolic perturbation increase QTc to a similar degree, and their co-existence exerts an additive effect. These effects are not modulated by individuals’ genetics. Metabolic ill-health is associated with a higher OR for VA than obesity.https://www.frontiersin.org/articles/10.3389/fcvm.2022.939156/fullobesitymetabolic syndromeQTc intervalventricular arrhythmiapolygenic risk score |
| spellingShingle | Kiran Haresh Kumar Patel Xinyang Li Xiao Xu Lin Sun Maddalena Ardissino Prakash P. Punjabi Sanjay Purkayastha Nicholas S. Peters James S. Ware Fu Siong Ng Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank Frontiers in Cardiovascular Medicine obesity metabolic syndrome QTc interval ventricular arrhythmia polygenic risk score |
| title | Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank |
| title_full | Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank |
| title_fullStr | Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank |
| title_full_unstemmed | Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank |
| title_short | Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank |
| title_sort | increasing adiposity is associated with qtc interval prolongation and increased ventricular arrhythmic risk in the context of metabolic dysfunction results from the uk biobank |
| topic | obesity metabolic syndrome QTc interval ventricular arrhythmia polygenic risk score |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.939156/full |
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