The effect of exercise training on vascular endothelial function and cardiac autonomic control in patients with coronary artery disease and diabetes

Abstract

Cardiac autonomic neuropathy (CAN) is a significant complication encountered in diabetic patients. Chapter 1 introduces CAN and its potential risk factors. For example, previous data identified that age, diabetes duration, and glycemic control all are associated with CAN. Furthermore, coronary artery disease (CAD), another diabetic complication, and CAN have a bidirectional relationship; occurrence of one condition may predict the other. In Chapter 4, we explored the prevalence of CAN in a cohort of diabetic patients with CAD. Using a battery of clinical autonomic function tests to assess 52 patients, CAN was diagnosed in 30 patients. Those with CAN had a higher resting diastolic blood pressure (77 ± 11 mmHg vs. 68 ± 18 mmHg, p=0.04), but were otherwise not significantly different in terms of sex, age, diabetes duration, medication use, fasting blood glucose, or HbA1c. Binary logistic regression analysis showed that resting diastolic blood pressure was a significant predictor of CAN in this cohort of patients (OR 1.152, 95% CI 1.018-1.304, p=0.025), after adjusting for sex, age, diabetes duration, HbA1c, medications, resting heart rate, and resting systolic blood pressure. Chapter 2 introduces the concept of high-intensity interval training (HIT) – an aerobic exercise training method that is becoming increasingly studied in exercise rehabilitation of cardiac patients. However, its effects on vascular endothelial function and cardiovascular autonomic function are still not yet fully elucidated. Therefore, in Chapter 5, an RCT was conducted in diabetic patients who had CAD. These patients were randomized to three study arms – HIT, MCT, CTRL – and underwent eight weeks of high-intensity interval training, eight weeks of moderate intensity continuous aerobic exercise, or no supervised exercise for eight weeks, respectively. 38 patients were included (HIT n=14; MCT n=11; CTRL n=13). Vascular endothelial function, measured by flow-mediated dilation (FMD), significantly improved in the exercised groups (HIT: 6.32 ± 4.20% vs. 11.61 ± 5.03%, p=0.003; MCT: 8.01 ± 4.32% vs. 12.63 ± 4.56%, p=0.018), although there were no inter-group differences (all p>0.05). There were no differences in CAN score sum, heart rate variability (HRV) and heart rate recovery (HRR) within groups between baseline and after intervention, and between groups in terms of change in these parameters. However, change in FMD was negatively correlated with change in CAN score (Pearson’s r=-0.438, p<0.01). In conclusion, CAN was not uncommon in this cohort of Chinese diabetic patients with CAD, although its occurrence was not significantly associated with or predicted by traditional CAN risk factors. In terms of management of these patients, exercise training is an important intervention. Though significant changes in cardiac autonomic function were not seen, exercise training is able to ameliorate vascular endothelial dysfunction in diabetic patients with CAD. High-intensity interval training may be pursued as an alternate aerobic exercise training modality in cardiac rehabilitation, as the two exercise modalities confer similar effects on vascular endothelial function, cardiac autonomic function, and clinical parameters.