Effects on heart rate variability of metoprolol supplementary to ongoing ACE-inhibitor treatment in Type I diabetic patients with abnormal albuminuria

Abstract

difference in heart rate between inspiration and expiration; LF, square root of power of the low frequency oscillation; LF power, power of the low frequency oscillation; Mean RR, mean of all normal RR intervals; Mean RR D-N, difference between awake and sleep time in mean RR; RSA, respiratory sinus arrhythmia; SDANN, standard deviation of the mean RR in all 5 min segments in a 24 h period; SDNN, standard deviation of all normal RR intervals; SDNN index, mean of SD's calculated on 5 min of RR intervals during a 24 h period; SE, standard error; sNN6%, number of successive RR interval differences > 6%, standardized to 24 h; sNN50, number of successive RR interval differences > 50 ms, standardized to 24 h; UAE, urine albumin excretion. AbstractAims/hypothesis. Diabetic nephropathy is associated with a high risk of cardiac mortality including sudden death. This is presumably related to an imbalance between sympathetic and parasympathetic tone resulting in a decreased heart rate variability (HRV). In nondiabetic patients a decreased HRV is known to be a strong predictor of cardiovascular death. Studies in non-diabetic patients have shown that β-blockers improve HRV parameters known to reflect parasympathetic function. The aim of our study was to investigate effects of additional β-blocker treatment on: cardiac autonomic function, blood pressure, and urine albumin excretion in ACE-inhibitor treated Type I (insulin-dependent) diabetes mellitus patients with abnormal albuminuria. Methods. We studied the effects of 6 weeks treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in 20 patients participating in a randomised, placebo controlled, double blind, crossover trial. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, Corresponding author: Dr. E. Ebbehøj, Medical Department M (Diabetes and Endocrinology), Aarhus Kommunehospitalet, DK-8000 Aarhus Denmark, E-mail: e.ebbehoj@dadlnet.dk Abbreviations: AMBP, Ambulatory blood pressure; CCVHF, coefficient of component variance for HF; CCVLF, coefficient of component variance for LF; HF, square root of power of the high frequency oscillation; HF power, power of the high frequency oscillation; HRV, heart rate variability; HRV index, geometric index of total variability in a 24 h period; I-E diff, Diabetologia (2002) 45:965-975 DOI 10.1007 Effects on heart rate variability of metoprolol supplementary to ongoing ACE-inhibitor treatment in Type I diabetic patients with abnormal albuminuria 24-h ambulatory blood pressure recording, and 24-h fractionated urine collections. Heart rate variability was assessed by four different methods; ambulatory HRV analysis was carried out by spectral and time domain analysis, and on days of investigation short-term spectral analysis and bed-side tests were carried out. Results. Metoprolol treatment improved in vagal tone assessed by short-term spectral analysis. The 24-h ambulatory HRV analysis showed improvement in some parameters reflecting vagal function. A minor decrease in...

Effects of metoprolol on QT interval and QT dispersion in Type 1 diabetic patients with abnormal albuminuria

“…In experimental and in spontaneous nocturnal hypoglycaemia, prolongation in QTc has been demonstrated [32,33], and pre-treatment with a beta blocker demonstrably prevented abnormal repolarisation during experimental hypoglycaemia [32]. We have previously shown that it is possible to improve heart rate variability parameters by B1-selective beta blockade [19]. This study now shows that it is also possible to reduce the QTc interval by B1-selective beta blockade.…”

“…The supplementary beta blocker treatment caused no change in systolic AMBP (daytime run-in 134±11 mm Hg, daytime placebo 135±12 mm Hg, daytime metoprolol 133± 10 mm Hg, p=NS) but did cause a decrease in daytime diastolic AMBP (daytime run-in 82±9 mm Hg, daytime placebo 83±8 mm Hg, daytime metoprolol 80±8 mm Hg, p=0.04) and an improvement in HRV parameters reflecting parasympathetic modulation (for details, see [19]). …”

“…Data on heart rate variability (HRV), urine albumin excretion (UAE) and ambulatory blood pressure (AMBP) have been published previously [19].…”

Cardiac Autonomic Neuropathy and Early Progressive Renal Decline in Patients with Nonmacroalbuminuric Type 1 Diabetes

“…Autonomic dysfunction also correlates with higher-range normoalbuminuria in patients with type 1 diabetes, suggesting a possible role for SNS activation in the transition from normo-to microalbuminuria (39) and activation of intrarenal RAAS, intraglomerular hypertension, and hyperfiltration in animals and in humans with type 1 diabetes (40)(41)(42). Therapeutic interventions using pharmacologic SNS blockade in type 1 diabetes resulted in lower BP and improved HRV (43). Meanwhile, in streptozotocin-induced diabetic rats, renal hyperfiltration can be prevented with sympathetic renal denervation (40).…”

Acute angiotensin-converting enzyme inhibition evokes bradykinin-induced sympathetic activation in diabetic rats

“…Theoretically, adding a central sympatholytic agent to ACE inhibition therapy could maximize the beneficial effects of ACE inhibition. In this regard, Ebbehoj et al (8) have shown that adding ␤-blocker treatment to concurrent ACE inhibition in patients with Type I diabetes improved autonomic function. Fig.…”