G Nyberg

EFFECT ON MORTALITY OF METOPROLOL IN ACUTE MYOCARDIAL INFARCTION: A Double-blind Randomised Trial

The effect of metoprolol on mortality was compared with that of placebo in a double blind randomised trial in patients with definite or suspected acute myocardial infarction. Treatment with metoprolol or placebo started as soon as possible after the patients arrival in hospital and was continued for 90 days. Metoprolol was given as a 15 mg intravenous dose followed by oral administration of 100 mg twice daily. 1395 patients (697 on placebo and 698 on metoprolol) were included in the trial. Definite acute myocardial infarction developed in 809 and probable infarction in 162. Patients were allocated to various risk groups and within each group patients were randomly assigned to treatment with metoprolol or placebo. There were 62 deaths in the placebo group (8.9%) and 40 deaths in the metoprolol group (5.7%), a reduction of 36% (p less than 0.03). Mortality rates are given according to the treatment group to which the patients were initially randomly allocated.

Effect of metoprolol on indirect signs of the size and severity of acute myocardial infarction

In a double-blind randomized trial, 1,395 patients with suspected acute myocardial infarction (MI) were investigated to evaluate the possibility of limiting indirect signs of the size and severity of acute MI with the beta 1-selective adrenoceptor antagonist metoprolol. Metoprolol (15 mg) was given intravenously and followed by oral administration for 3 months (200 mg daily). Placebo was given in the same way. The size of the MI was estimated by heat-stable lactate dehydrogenase (LD[EC 1.1.1.27]) analyses and precordial electrocardiographic mapping. Lower maximal enzyme activities compared with placebo were seen in the metoprolol group (11.1 +/- 0.5 mukat X liter-1) when the patient was treated within 12 hours of the onset of pain (13.3 +/- 0.6 mukat X liter-1; n = 936; p = 0.009). When treatment was started later than 12 hours, no difference was found between the 2 groups. Enzyme analyses were performed in all but 20 patients (n = 1,375). Precordial mapping with 24 chest electrodes was performed in patients with anterior wall MI. The final total R-wave amplitude was higher and the final total Q-wave amplitude lower in the metoprolol group than in the placebo group. Patients treated with metoprolol less than or equal to 12 hours also showed a decreased need for furosemide, a shortened hospital stay, and a significantly reduced 1-year mortality compared with the placebo group, whereas no difference was observed among patients treated later on. After 3 months, however, there was a similar reduction in mortality among patients in whom therapy was started less than or equal to 12 hours and greater than 12 hours after the onset of pain. The results support the hypothesis that intravenous metoprolol followed by oral treatment early in the course of suspected myocardial infarction can limit infarct size and improve long-term prognosis.

Increased arterial stiffness and indication of endothelial dysfunction in long‐standing rheumatoid arthritis

Objective: Atherosclerotic progression is accelerated in rheumatoid arthritis (RA). We evaluated arterial stiffness and endothelial dysfunction in RA patients and controls by pulse wave analysis (PWA). Methods: Thirty RA patients with long‐standing disease and 30 age‐ and sex‐matched controls were examined using applanation tonometry of the radial artery before and after vasodilation by terbutaline (endothelium dependent) and nitroglycerin (endothelium independent). The aortic augmentation index (AIx) and time to reflected wave (transit time, Tr) were measured. Using the peripheral pulse curve, the stiffness index (SI) and the reflectance index (RI) were calculated. Tr and SI predominantly reflect large artery stiffness, whereas Aix and RI also reflect small vessel resistance. The PWA measurements were assessed in relation to adhesion molecules [soluble platelet endothelial cell adhesion molecule‐1 (sPECAM‐1), soluble vascular cell adhesion molecule‐1 (sVCAM‐1) and soluble intracellular adhesion molecule‐1 (sICAM‐1)], selectins (E, L and P), and inflammation [erythrocyte sedimentation rate (ESR), haptoglobin, interleukin (IL)‐6, IL‐1 receptor antagonist (IL‐1‐Ra), IL‐2‐soluble receptor (IL‐2sR), and tumour necrosis factor receptors‐I and ‐II (TNFR‐I and TNFR‐II)]. Results: RA patients had shorter Tr (p<0.05) and higher SI (p<0.001) than controls, indicating impaired large vessel compliance. After terbutaline, Tr remained shorter (p<0.05), while SI (p<0.01) and AIx (p<0.01) were higher. The post‐terbutaline changes in AIx and RI (ΔAIx, ΔRI), suggested to be the best PWA measurements of endothelial function, were smaller in RA patients (p = 0.06). In RA, L‐selectin and sVCAM‐1 correlated with ΔRI and L‐selectin also with ΔAIx. Both RI and AIx correlated at baseline with a retrospective inflammatory activity score. Conclusion: Arterial stiffness was increased in RA patients. Endothelial dysfunction was implicated and correlated with levels of soluble adhesion molecules. Small vessel resistance correlated with the long‐standing inflammatory load in RA.

Music structure determines heart rate variability of singers

Choir singing is known to promote wellbeing. One reason for this may be that singing demands a slower than normal respiration, which may in turn affect heart activity. Coupling of heart rate variability (HRV) to respiration is called Respiratory sinus arrhythmia (RSA). This coupling has a subjective as well as a biologically soothing effect, and it is beneficial for cardiovascular function. RSA is seen to be more marked during slow-paced breathing and at lower respiration rates (0.1 Hz and below). In this study, we investigate how singing, which is a form of guided breathing, affects HRV and RSA. The study comprises a group of healthy 18 year olds of mixed gender. The subjects are asked to; (1) hum a single tone and breathe whenever they need to; (2) sing a hymn with free, unguided breathing; and (3) sing a slow mantra and breathe solely between phrases. Heart rate (HR) is measured continuously during the study. The study design makes it possible to compare above three levels of song structure. In a separate case study, we examine five individuals performing singing tasks (1–3). We collect data with more advanced equipment, simultaneously recording HR, respiration, skin conductance and finger temperature. We show how song structure, respiration and HR are connected. Unison singing of regular song structures makes the hearts of the singers accelerate and decelerate simultaneously. Implications concerning the effect on wellbeing and health are discussed as well as the question how this inner entrainment may affect perception and behavior.

Erratum: Music structure determines heart rate variability of singers

[This corrects the article on p. 334 in vol. 4, PMID: 23847555.].

Importance of software version for measurement of arterial stiffness: Arteriograph as an example

Background Current guidelines recommend the measurement of arterial stiffness in terms of aortic pulse wave velocity (PWV) as an important cardio-vascular risk marker. Both aortic PWV and the aortic augmentation index (AIxao) can be measured using different techniques, e.g., the Arteriograph and SphygmoCor. A new version of the software for the Arteriograph (v. 3.0.0.1, TensioMed, Budapest, Hungary; Arteriograph II) is now available. We wanted to determine whether this improved software differs from the previous version (Arteriograph v. 1.9.9.12; Arteriograph I). We compared the estimated aortic PWV (ePWVao) and AIxao measured with both versions of Arteriograph software and analysed the agreement of these values with those measured by SphygmoCor (v. 7.01, AtCor Medical, Sydney, Australia). Methods Eighty-seven subjects without known cardio-vascular disease (23 men and 64 women) aged 54.2 ± 8.7 years (mean ± standard deviation; range 33–68 years) were included in the study. Estimated PWVao and AIxao were measured by both Arteriograph and SphygmoCor. We compared Arteriograph I and Arteriograph II with each other and with SphygmoCor. Results Estimated PWVao measured by Arteriograph II was lower than that measured by Arteriograph I, while the AIxao was higher. Divergence in ePWVao values was especially noted above 9 m/s. Estimated PWVao measured by Arteriograph II (7.2 m/s, 6.6–8.0 [median, 25th–75th percentile]) did not differ from that measured by SphygmoCor (7.1 m/s, 6.7–7.9 [median, 25th–75th percentile]). However, the AIao measured by Arteriograph II was significantly higher (P < 0.001). Conclusion Regularly upgraded software versions resulting from continuous technical development are needed for quality improvement of methods. However, the changes in software, even if the basic patented operational algorithm has not changed, may influence the measured values as shown in the present study. Therefore, attention should be paid to the software version of the method used when comparing arterial stiffness results in clinical settings or when performing scientific studies.