Insulin Resistance is Associated with Longitudinal Changes of Cardiac Repolarization Heterogeneity in Apparently Healthy Subjects

Introduction: Increased heterogeneity in ventricular repolarization is a risk factor of sudden cardiac death, but its natural history is unclear. Here we examined whether insulin resistance is associated with longitudinal change in ventricular repolarization heterogeneity in apparently healthy subjects. Methods: The study subjects were participants in health checkups in cohort 1 and cohort 2, which were followed up for 6 years and 5 years, respectively. Subjects with diabetes, cardiovascular disease, or renal disease at baseline were excluded from the analyses. As indices of insulin resistance, the homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride to HDL-cholesterol ratio (TG/HDL-C) were used in cohort 1 and cohort 2, respectively. Heterogeneity in ventricular repolarization was assessed by heart rate-corrected Tpeak-Tend interval in V5 (cTpTe), QT interval, and QT dispersion. In regression analyses, parameters with a skewed distribution were normalized by logarithmic transformation or by Box-Cox transformation. Results: In longitudinal analyses, Box-Cox-transformed cTpTe at the end of follow-up was weakly correlated with log HOMA-IR at baseline in cohort 1 (n=153, r=- 0.207, 95% CI - 0.354to- 0.050, p=0.010) and with log TG/HDL-C at baseline in cohort 2 (n=738, r=- 0.098, 95% CI - 0.169to- 0.026, p=0.008). Multiple regression analysis showed that indices of insulin resistance, but not glycosylated hemoglobin (HbA1c) or plasma glucose, at baseline were significant explanatory variables for cTpTe at the end of follow-up. Neither QT interval nor QT dispersion was correlated with metabolic parameters. Conclusion: Insulin resistance may be involved in the longitudinal increase of ventricular repolarization heterogeneity in apparently healthy subjects.