Relationships between reduced heart rate variability and pre-clinical cardiovascular disease in patients with type 2 diabetes

Aims Reduced heart rate variability (HRV), an early sign of diabetic cardiovascular autonomic neuropathy (CAN), is associated with worse cardiovascular outcomes. The objective was to evaluate relationships between HRV parameters and three pre-clinical cardiovascular disease markers (left ventricular hypertrophy [LVH], aortic stiffness and carotid atherosclerosis) in type 2 diabetes. Methods In a cross-sectional study, 313 patients with type 2 diabetes performed 24-h Holter monitoring, carotid ultrasonography (intima-media thickness and plaques measurements), aortic pulse wave velocity measurement and echocardiography (left ventricular mass index [LVMI] measurement). Time-domain HRV parameters were the standard deviation of all normal RR intervals (SDNN), the standard deviation of the averaged normal RR intervals for all 5 min segments (SDANN), the root mean square of differences between adjacent R-R intervals (rMSSD), and the percentage of adjacent R-R intervals that varied by >50 ms (pNN50). Multivariate linear and logistic regressions assessed associations between HRV parameters and the three markers of pre-clinical cardiovascular disease. Results Patients with reduced HRV had longer diabetes duration, greater prevalences of microvascular complications, lower physical fitness, and higher heart rate, glycated hemoglobin, albuminuria and LVMI than patients with normal HRV. On multivariate regressions, after adjustments for several confounders, reduced SDNN and SDANN were independently associated with LVH and aortic stiffness. No HRV parameter was associated with carotid atherosclerosis. Conclusions Two reduced HRV parameters, SDNN and SDANN, which reflect cardiovascular autonomic imbalance, were associated with LVH and aortic stiffness, markers of pre-clinical cardiovascular disease. These findings may offer insights into physiopathological mechanisms linking CAN to worse cardiovascular prognosis.