Atenolol's Inferior Ability to Reduce Central vs Peripheral Blood Pressure Can Be Explained by the Combination of Its Heart Rate-Dependent and Heart Rate-Independent Effects.

OBJECTIVE: Whether the inferior ability of atenolol to reduce central (aortic) compared to peripheral (brachial) blood pressure (BP) is related to its heart rate (HR)-dependent or -independent effects, or their combination, remains unclear. To provide further mechanistic insight into this topic, we studied the acute effects of atenolol versus nebivolol and ivabradine on systolic blood pressure amplification (SBPA; peripheral systolic BP minus central systolic BP) in a model of sick sinus syndrome patients with a permanent dual-chamber cardiac pacemaker in a nonrandomized single-blind single-group clinical trial. METHODS: We determined hemodynamic indices noninvasively (Sphygmocor XCEL) before and at least 3 h after administration of oral atenolol 50 or 100 mg, nebivolol 5 mg, or ivabradine 5 or 7.5 mg during atrial pacing at a low (40 bpm), middle (60 bpm), and high (90 bpm) HR level in 25 participants (mean age 65.5 years, 12 men). RESULTS: At the low HR level, i.e., when the drugs could exert their HR-dependent and HR-independent effects on central BP, only atenolol produced a significant decrease in SBPA (mean change 0.74 ± 1.58 mmHg (95% CI, 0.09-1.40; P = 0.028)), indicating inferior central vs peripheral systolic BP change. However, we observed no significant change in SBPA with atenolol at the middle and high HR levels, i.e., when HR-dependent mechanisms had been eliminated by pacing. CONCLUSION: The findings of our trial with a mechanistic approach to the topic imply that the inferior ability of atenolol to reduce central vs peripheral BP can be explained by the combination of its heart rate-dependent and -independent effects. This trial is registered with NCT03245996.

Heart rate reduction decreases central blood pressure in sick sinus syndrome patients with a permanent cardiac pacemaker.

Increased resting heart rate (HR) contributes to higher cardiovascular mortality and morbidity in the healthy as well as in people with cardiovascular diseases, possibly due to elevated blood pressure (BP) among other mechanisms. Data on the relationship between HR and central (aortic) BP remains controversial, however, and concerning ß-blockers, it has been proposed that pharmacological HR lowering is associated with augmentation of central BP. We aimed to study the role of pharmacologically unaffected HR on central BP indices in sick sinus syndrome patients with a permanent cardiac pacemaker in the HR range from 40 to 90 bpm. We included 27 subjects (mean age 65.8 ± 9.5 years, 12 men) with a dual-chamber pacemaker implanted due to sick sinus syndrome. We determined central hemodynamic indices noninvasively during an atrial pacing mode at low (40 bpm), middle (60 bpm), and high (90 bpm) HR levels with an oscillometric cuff-based device (Sphygmocor XCEL). There was no difference in central systolic BP at the middle versus the high HR level (mean 121.2 ± 13.0 and 121.2 ± 12.1 mmHg, respectively, P = 0.9), but at the low HR level, it was significantly lower than at the middle HR level (mean 117.2 ± 13.1 and 121.2 ± 13.0 mmHg, P < 0.01). Our acute study provides evidence to suggest that at a HR of <60 bpm, sick sinus syndrome patients may have a lower central BP than at a higher HR, despite the proposed augmenting effects of low HR on central BP.

Increasing incidence of childhood-onset type 1 diabetes mellitus among Estonian children in 1999-2006. Time trend analysis 1983-2006.

BACKGROUND: The incidence of childhood-onset type 1 diabetes mellitus (T1DM) among Estonian children under 15 years of age was 10.1 per 100,000 per year in 1983-1990 and 12.2 per 100,000 per year in 1991-1998 with the highest incidence in age-group 10.0-14.9 years in both periods. From 1983 to 1998, the incidence increased most rapidly in age-group 0-4.9 years. OBJECTIVE: To determine the incidence of T1DM among Estonian children in 1999-2006 and to compare the results with the data from 1983 to 1998. SUBJECTS AND METHODS: In 1999-2006, population-based incidence data were collected from two centers where all children with T1DM are seen after the diagnosis. Data for earlier periods were obtained from previously published data. Subjects were divided into three age-groups: 0-4.9 years, 5.0-9.9 years and 10.0-14.9 years. RESULTS: Between 1999 and 2006, 310 new cases of T1DM were diagnosed in Estonian children aged 0-14.9 years. The age-standardized incidence rate for that period was 17.2 [95% confidence interval (CI) 13.1-21.2]. The incidence was the highest, 21.2 (95% CI 17.7-25.3) in age-group 5.0-9.9 years. Over the time period 1983-2006, the incidence of childhood-onset T1DM in Estonian children under 15 years of age increased annually by an average 3.3% with the most rapid annual increase-9.3%-occurring in the youngest age-group. CONCLUSIONS: The incidence of childhood-onset T1DM in Estonia continues to rise and the age of onset of the disease becomes younger.