Short- and long-term effect of simvastatin therapy on the heterogeneity of cardiac repolarization in diabetic patients

The interlead variability of QT interval in the 12-lead electrocardiogram, QT dispersion (QTd), has been shown to reflect dispersion of ventricular refractoriness and may provide a measure of arrhythmogenic potential in diabetic patients. QTd and heart rate corrected QTd (QTcd) were also proposed to be accurate predictors of cardiac death in patients with diabetes. In recent years, experimental and clinical evidence demonstrates that statins exert antiarrhythmic properties. Therefore, in the present study, we have examined whether simvastatin treatment has any effect on the QTd and QTcd in patients with diabetes mellitus. Sixty type 2 diabetic patients without known coronary artery disease and low-density lipoprotein cholesterol >100 mg/dl and 30 age and sex-matched non-diabetic controls were included in a prospective study. Out of 60 diabetic patients, 30 were treated with simvastatin 40 mg/day for 1 year and the remaining 30 subjects were served as diabetic controls. No lipid lowering therapy was administered to the diabetic and the non-diabetic controls. QTd and QTcd of treated diabetics and the non-diabetic controls were measured at baseline, 6, 12 weeks and at 1 year. QTd and QTcd of the diabetic controls were obtained at baseline, 6 and 12 weeks. Both QTd and QTcd were significantly greater in patients with the diabetes than in the non-diabetic controls at baseline (52 +/- 13 ms vs. 41 +/- 12 ms, p < 0.001 and 62 +/- 17 ms vs. 42 +/- 11 ms, p < 0.001, respectively). Simvastatin therapy significantly decreased both QTd and QTcd at the end of first year compared to baseline (51 +/- 15 ms vs. 33 +/- 11 ms, p < 0.001 and 60 +/- 18 ms vs. 38 +/- 12 ms, p < 0.001, respectively). No significant change were found in QTd and QTcd in the non-diabetic (p = 0.29 and p = 0.87 by ANOVA, respectively) and in the diabetic controls (p = 0.72 and p = 0.57, by ANOVA, respectively). This study suggests for the first time that simvastatin treatment in diabetic patients with hyperlipidemia is associated with an improvement in the heterogeneity of cardiac repolarization. This may be one of the mechanisms for the reduction in clinical events reported in the survival studies with statins. Further prospective randomized studies are warranted to confirm our findings. (C) 2008 Elsevier Ltd. All rights reserved.