Reliability of heart rate in reflecting cardiac sympathetic overdrive in type 2 diabetes mellitus

Abstract

Purpose: Clinical trials have shown that in type 2 diabetes mellitus (T2D) resting office heart rate (HR) values > 70 beats/minute are associated with an increased cardiovascular risk, a worse prognosis and an unfavorable outcome. The present study was aimed at investigating whether the above mentioned treshold HR values reflect a sympathetic overdrive of marked degree.

Methods: In 58 T2D patients (age range: 39-57 years) without signs of autonomic neuropathy and in 52 age-matched healthy controls, we assessed muscle sympathetic nerve activity (MSNA, microneurography) and venous plasma norepinephrine (NE, HPLC), subdividing the study population in different subgroups according to their clinic and 24-h HR values.

Results: In T2D progressively greater clinic and 24-h HR values were accompanied by progressive increases in MSNA and NE. HR cutoff values indicated by clinical trials as associated with an increased cardiovascular risk (> 70 beats/minute) were accompanied by MSNA values significantly higher than those detected in patients with lower HR, this being the case also for NE. In T2D both MSNA and NE were significantly related to clinic (r = 0.93, P < 0.0001 and r = 0.87, P < 0.0001, respectively) and 24-h (r = 0.92, P < 0.0001 and r = 0.84, P < 0.0001, respectively) HR. The MSNA and NE behaviour observed in T2D was not detected in healthy controls.

Conclusions: In T2D clinic HR values allow to detect patients with a greater sympathetic overactivity. Considering the adverse clinical impact of the sympathetic overdrive on prognosis, our data emphasize the need of future studies investigating the potential usefulness of lifestyle and pharmacological interventions exerting sympathomodulatory effects.

Keywords: Cardiovascular risk; Heart rate; Plasma norepinephrine; Sympathetic activity; Sympathetic nerve traffic; Type 2 diabetes.

Fig. 1

Individual and average values (± SEM) of heart rate (HR), muscle sympathetic nerve traffic (MSNA), and venous plasma norepinephrine (NE) in the groups of patients with type 2 diabetes mellitus (T2D) with clinic HR (upper panels) or 24-h HR (lower panels) values below 70 beats/minute, between 70 and 79 beats/minute and ≥ 80 beats/minute. Bs/min indicates bursts frequency over time (minute). *P < 0.01and **P < 0.001 refer to the statistical significance between groups

Fig. 2

Left: Regressing clinic heart rate (HR) on muscle sympathetic nerve traffic (MSNA), expressed as bursts frequency over time (bursts per minute, bs/min, upper panel) and plasma norepinephrine (NE, lower panel) in 58 patients with T2D. Correlation coefficients (r) and P values are shown. Right: Regressing 24-h HR on MSNA, expressed as bursts frequency over time (bursts per minute, upper panel) and venous plasma NE (lower panel) in 58 patients with type 2 diabetes mellitus. Correlation coefficients (r) and P values are shown

Fig. 3

Individual and average values (± SEM) of heart rate (HR), muscle sympathetic nerve traffic (MSNA), and venous plasma norepinephrine (NE) in the groups of healthy subjects with clinic HR (upper panels) or 24-h HR (lower panels) values below 70 beats/minute, between 70 and 79 beats/minute and ≥ 80 beats/minute. Bs/min indicates bursts frequency over time (minute). *P < 0.01 and **P < 0.001 refer to the statistical significance between groups