Heart-rate recovery as a clinical marker of cardiovascular autonomic dysfunction in diabetic patients

Abstract

Dear Sir, We read with great interest the recent article by Shinohara et al., published in September 2008, concerning the role of interleukin-6 (IL-6) levels in cardiovascular autonomic dysfunction in patients with type 2 diabetes [1]. The study included 80 patients with type 2 diabetes without organic heart disease who were assigned to a high IL-6 group (>2.5 pg/ml, n=40, age 59±12 years) or a non-high IL-6 group (<2.5 pg/ml, n=40, age 61±12 years). Cardiac autonomic function was assessed by several methods including baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations and I-metaiodobenzylguanidine (MIBG) scintigraphy. The body mass index (BMI), fasting insulin levels, and homeostasis model assessment index values were higher in the high IL-6 group than in the non-high IL-6 group (p<0.01), while early and delayed I-MIBG myocardial uptake values were lower (p<0.01) and the percent washout rate was higher (p<0.05) in the high IL-6 group [1]. Multiple regression analysis revealed that the IL-6 level was independently predicted by the BMI and myocardial uptake of I-MIBG during the delayed phase [1]. Thus, the authors concluded that elevated IL-6 levels are associated with depressed cardiovascular autonomic function and obesity in patients with type 2 diabetes [1]. We refer to our experience investigating the clinical value of heart-rate recovery (HRR) in diabetic patients. The rise in heart rate during exercise is considered to be a direct consequence of sympathetic activation combined with parasympathetic withdrawal, whereas the decline in heart rate immediately after exercise is thought to be a function of reactivation of parasympathetic tone [2]. The reduction in heart rate from its value at peak exercise to the rate 1 min later is generally taken as the HRR [3]. The autonomic nervous system has a profound effect on myocardial pathophysiology, while autonomic neuropathy is a common complication in diabetic patients, particularly in those using insulin [4, 5]. In addition, it has been previously reported that fasting plasma glucose and plasma insulin levels are closely correlated with changes in cardiac autonomic function and impaired HRR [4]. The pathophysiology of abnormal HRR involves the inability to slow the heart immediately after exercise, which has been previously shown to be a marker of decreased vagal activity [2, 3]. Attenuated HRR after exercise testing has been found to be an independent predictor of cardiac and all-cause mortality in patients referred for exercise electrocardiography, while diabetes mellitus is associated with increased mortality from cardiovascular disease [3, 5–7]. Studying 206 diabetic patients, we have found a significant correlation (p<0.001) between HRR and myocardial ischaemia scintigraphic variables (summed stress score and summed difference score) [8]. Moreover, the calculation of HRR value during exercise testing could provide additional information and an incremental value (compared to clinical and exercise testing data) for the detection of myocardial ischaemia [8]. In addition, we have found a significant association between chronotropic variables during exercise testing and HRR [8]. Furthermore, we have recently reported our results of a study evaluating the usefulness of HRR after treadmill testing as a long-term prognostic marker of cardiovascular morbidity and mortalEur J Nucl Med Mol Imaging (2009) 36:320–321 DOI 10.1007/s00259-008-0982-z