Effect of beta-blocker therapy on heart rate response in patients with hypertension and newly diagnosed untreated obstructive sleep apnea syndrome

Abstract

Background: Beta1-receptor antagonists (BBs) are commonly administered in the treatment of cardiovascular disease (CVD). The reported benefits of BB use in CVD patients with concomitant obstructive sleep apnea (OSA) may be limited by their impact on apnea-induced bradycardias. Therefore the aim of the study was to test the influence of BBs on periapneic heart rate (HR) fluctuations in hypertensive patients with newly-detected and untreated OSA.

Methods: We studied 88 hypertensive patients (56 on BBs and 32 BB naive) with newly-diagnosed moderate-to-severe OSA who were free of major pulmonary comorbidities and did not require antiarrhythmic therapy. ECGs recorded during sleep were investigated for heart rate (HR) responses to apneas allowing to compare extreme HR accelerations and decelerations between the groups.

Results: Average sleep-time HR was comparable in BB-naive (BB-) and BB-treated (BB+) patients. Direct comparisons showed that HR decelerations were also similar in the two subgroups (53.8±9.6 vs. 54.4±7.8 bpm; P=0.78, for BB- and BB+, respectively) however, BBs blunted the OSA-induced HR accelerations (82.3±12.2 vs. 74.3±10.0; P=0.003). After adjusting for baseline HR and magnitude of desaturations, HR decelerations were more evident in BB-naive group whereas tachycardic responses remained blunted in the BB+ group. The incidence of ectopies and conduction abnormalities were comparable across two groups.

Conclusions: Beta-blockers do not potentiate apnea-induced HR decelerations, attenuate apnea-induced increases in heart rate and do not influence incidence of ectopies and conduction abnormalities in patients with hypertension and moderate-to-severe, untreated OSA.

Keywords: Beta-blockers; Bradycardia; Heart rate control; Obstructive sleep apnea; Tachycardia.

Figure 1

Study flow-chart.

Figure 2. Example of recurrent cyclic variations of the heart rate and apnea-related bradyarrhythmias

Figure depicts reoccurring heart rate accelerations, decelerations, and bradyarrhythmias associated with sleep apneic episodes. The tracings represent following signals (from top to bottom): nasal airflow (pressure cannula), thorax and abdomen movements (inductive belts), ECG, heart rate, and SpO2 (pulse oximetry). The extreme decelerations were calculated as averaged three longest RR intervals while sinus rhythm occurring in apnea-corresponding ECG tracing (red rectangle window), and the HR sinus accelerations were calculated as averaged three shortest RR-intervals while patient attempted rescue breathing (blue rectangle window). The bradyarrhythmias resulting from the atrioventricular blocks were assessed separately (here: AVB 2^nd degree 2:1).

Figure 3

Comparison of periapneic maximal increases (left panel), and minimal decreases (right panel) of the heart rates with relation to ongoing beta-blocker treatment. Unpaired t-tests.

Figure 4. Comparison of cyclic variations of heart rate and relationships to the dosage of beta-blocker therapy and the presence of coronary artery disease. One-way ANOVA, P=0.001

Boxes represent mean values, and whiskers standard errors of the mean. BBs = beta-blockers; BBs100% - full registered BBs dosage; BBs50% - half registered dosage according to Summaries of Products Characteristics. CAD - coronary artery disease. P-values refer to post-hoc Dunnett's tests against BBs-naive group (reference group).

Figure 5. Apnea-related ectopies, and conduction abnormalities occurrence in patients with and without beta-blocker treatment

Panels represents the comparison of the prevalence of (left) ectopies resulting in acceleration of the HR, and (right) conduction abnormalities causing RR interval prolongation >2000ms or decelerated non-sinus rhythm.