Patel Kiran Haresh Kumar, Li Xinyang, Xu Xiao, Sun Lin, Ardissino Maddalena, Punjabi Prakash P, Purkayastha Sanjay, Peters Nicholas S, Ware James S, Ng Fu Siong
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Imperial College London, London, United Kingdom.
Front Cardiovasc Med. 2022 Jun 29;9:939156. doi: 10.3389/fcvm.2022.939156. eCollection 2022.
Small-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.
Firstly, using the UK Biobank, the association between adiposity and QTc interval was assessed in participants with a resting 12-lead ECG ( = 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 (s) 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.
Adiposity 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.
小规模研究已将肥胖（Ob）和代谢性健康不良与致心律失常性复极异常联系起来。这些现象是否在人群层面上存在，是否受个体遗传因素的调节，以及是否会增加室性心律失常（VA）的风险尚不清楚。
首先，利用英国生物银行，在有静息12导联心电图的参与者（n = 23,683）中评估肥胖与QTc间期之间的关联，并开发了一个多基因风险评分（PRS）来研究遗传因素的任何调节作用。参与者还根据是否存在肥胖（+）或不存在肥胖（-）以及是否存在代谢性不健康（MU+）或不存在代谢性不健康（MU-）被分为四种表型。QTc与体重指数（BMI）、体脂（BF）、腰臀比（WHR）以及臀围和腰围呈正相关。个体的遗传因素对肥胖增加导致的QTc延长效应没有显著的调节作用。与既无肥胖又无代谢紊乱的个体（Ob-MU-）相比，无肥胖但有代谢紊乱的个体（Ob-MU+）和仅有肥胖的个体（Ob+MU-）的QTc间期相对更长，且两者共存（Ob+MU+）对QTc间期有累加效应。其次，对于英国生物银行中的502,536名参与者，利用他们过去病历计算上述四种临床表型发生VA的比值比（OR）。以Ob-MU-为参照，Ob-MU+男性和女性发生VA的OR分别为5.96（95%CI：4.70-7.55）和5.10（95%CI：3.34-7.80）。Ob+MU+男性和女性的OR分别为6.99（95%CI：5.72-8.54）和3.56（95%CI：2.66-4.77）。
肥胖和代谢紊乱对QTc的增加程度相似，且两者共存会产生累加效应。这些效应不受个体遗传因素的调节。与肥胖相比，代谢性健康不良与发生VA的更高OR相关。
