Abstract

Previous experimental studies showed that increasing high-density lipoprotein cholesterol (HDL) cholesterol shortens cardiac ventricular repolarization and the QT interval corrected for heart rate (QTc). However, little is known about the epidemiological relationship between HDL and QTc. The potential antiarrhythmic effect of HDL cholesterol remains a speculative hypothesis. In this cross-sectional population based study in adults living in the Italian-speaking part of Switzerland, we aimed to explore the association between HDL cholesterol and the QTc interval in the general population. A total of 1202 subjects were screened. electrocardiogram (ECG) recordings, measurements of lipid parameters and other laboratory tests were performed. QTc was corrected using Bazett’s (QTcBaz) and Framingham (QTcFram) formulas. HDL was categorized according to percentile distributions: <25th (HDL-1; ≤1.39 mmol/L); 25th–<50th (HDL-2; 1.40–1.69 mmol/L); 50th–<75th (HDL-3; 1.69–1.99 mmol/L); and ≥75th (HDL-4; ≥2.0 mmol/L). After exclusion procedures, data of 1085 subjects were analyzed. Compared with the HDL reference group (HDL-1), HDL-2 and HDL-3 were associated with a reduction of QTcBaz and QTcFram duration in crude (HDL-2, QTcBaz/QTcFram: β-11.306/–10.186, SE 4.625/4.016; p = 0.016/0.012; HDL-3, β-12.347/–12.048, SE 4.875/4.233, p = 0.012/<0.001) and adjusted (HDL-2: β-11.697/–10.908, SE 4.333/4.151, p < 0.001/0.010; HDL-3 β-11.786/–11.002, SE 4.719/4.521, p = 0.014/0.016) linear regression models in women. In adjusted logistic regression models higher HDL, were also associated with lower risk of prolonged QTcBaz/QTcFram (HDL-2: OR 0.16/0.17, CI 0.03–0.83/0.47–0.65; HDL-3: OR 0.10/0.14, CI 0.10–0.64/0.03–0.63) in women. Restricted cubic spline analysis confirmed a non linear association (p < 0.001). The present findings indicate an epidemiological association between HDL cholesterol and QTc duration. To draw firm conclusions, further investigations in other populations and with a prospective cohort design are needed.

Highlights

  • In recent years, an intriguing antiarrhythmic effect of high-density lipoprotein cholesterol (HDL) was postulated

  • The potential antiarrhythmic effect of HDL cholesterol remains a speculative hypothesis. In this cross-sectional population based study in adults living in the Italian-speaking part of Switzerland, we aimed to explore the association between HDL cholesterol and the QT interval corrected for heart rate (QTc) interval in the general population

  • Overall in the logistic regression analyses, where HDL cholesterol was categorized in percentiles, we found that in females, HDL-cholesterol higher percentiles (HDL-2 and HDL-3) were associated with reduced risk of QTcFram and QTc was corrected using Bazett (QTcBaz) prolongation compared with the lowest percentile (HDL-1)

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Summary

Introduction

An intriguing antiarrhythmic effect of high-density lipoprotein cholesterol (HDL) was postulated. Studies in animal models found a direct association between post-infarction plasma. HDL levels and ischemia-reperfusion related ventricular arrhythmias (VA), with high plasma HDL levels exerting a protective role [1,2]. Low HDL cholesterol levels are linked with increased risk of sudden cardiac death [3,4,5], and several reports have postulated a correlation between plasma HDL concentrations and the onset of fatal arrhythmias [6,7]. A previous experimental study revealed that increasing HDL cholesterol shortens cardiac ventricular repolarization in isolated cardiomyocytes and the QT interval corrected for heart rate (QTc) in healthy humans [14] Ventricular tachyarrhythmias often precede cardiovascular death and the prolongation of the ventricular cardiac repolarization time, which often underlies these rhythm disturbances, is one of the predictors of sudden cardiac death [11,12,13].

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