Effects of Liraglutide on Heart Rate and Heart Rate Variability: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

OBJECTIVE: Reduced heart rate variability (HRV) and increased heart rate (HR) have been associated with cardiovascular mortality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) increase HR, and studies have suggested that they may reduce HRV. We examined the effect of the GLP-1 RA liraglutide on HRV and diurnal variation of HR in overweight patients with newly diagnosed type 2 diabetes (T2D) and stable coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: Liraglutide or placebo was administrated to a backbone therapy of metformin in this double-blind, placebo-controlled 12 + 12-week crossover study. SD of beat-to-beat (NN) intervals (SDNN) was assessed by 24-h Holter monitoring as a measure of HRV. Diurnal HR variation and sympathovagal balance analyzed by root mean square of successive differences (RMSSD) in NN intervals and high-frequency (HF) and low-frequency (LF) power were assessed. RESULTS: Compared with placebo, liraglutide decreased SDNN in 27 subjects (-33.9 ms; P < 0.001, paired analysis); decreased RMSSD (-0.3 log-ms; P = 0.025); and increased the mean HR (8.1 beats/min; P = 0.003), daytime HR (5.7; P = 0.083), and nighttime HR (6.3; P = 0.026). In a multivariable regression analysis, the decrease in SDNN remained significant after adjustment for metabolic and HR changes. Liraglutide reduced HF power (-0.7 log-ms2; P = 0.026) without any change in LF/HF ratio. CONCLUSIONS: In overweight patients with CAD and newly diagnosed T2D, liraglutide increased HR and reduced HRV despite significant weight loss and improvement in metabolic parameters. The increase in nightly HR in conjunction with a decrease in parameters of parasympathetic activity suggests that liraglutide may affect sympathovagal balance.

Atrial ectopy and N-terminal pro-B-type natriuretic peptide as predictors of atrial fibrillation: a population-based cohort study.

AIMS: The risk of incident atrial fibrillation (AF) can be estimated by clinical parameters in the Framingham AF risk model. Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and increased rate of premature atrial contractions (PACs) have been shown to be associated with AF, but the additive value of both of these biomarkers in the Framingham AF risk model has not been fully examined. METHODS AND RESULTS: A total of 646 subjects from the Copenhagen Holter Study (mean age 64.4 ± 6.8 years, 41.6% women) with no history of prior AF, stroke or cardiovascular disease were followed for the diagnosis of incident AF or death (median follow-up time 14.4 years). Median NT-proBNP was 6.7 pmol/L (IQR: 3.6-13.5), median PAC count was 1.4 beats/h (IQR: 0.6-4.5), 71 (11.0%) subjects developed AF, and 244 (37.8%) died. Multiple Cox regression including Framingham AF risk score, log-transformed NT-proBNP, and log-transformed PAC showed a significant increase in AF hazard risk [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.14-1.85, P = 0.002; HR 1.23, 95% CI 1.09-1.39, P = 0.001]. The addition of PAC to the Framingham AF risk model significantly improved the time-dependent area under the receiver operating characteristic curve (AUC 65.6 vs. 72.6; P = 0.008), while the addition of NT-proBNP did not. CONCLUSION: Atrial fibrillation risk discrimination was significantly improved by the addition of PAC to the Framingham AF risk model, but not by the addition of NT-proBNP.