Association of circulating irisin and cardiopulmonary exercise capacity in healthy volunteers: results of the Study of Health in Pomerania.

BACKGROUND: Irisin, a recently discovered myokine, is assumed to be secreted by muscle cells in response to exercise and is involved in the regulation of energy metabolism by browning white adipose tissue cells. However, due to the fact that previous studies revealed conflicting results concerning the association between irisin and exercise, the aim of the present study was to investigate the potential relationship between irisin and exercise capacity in a population-based setting. METHODS: From the population-based Study of Health in Pomerania (SHIP-TREND) 334 men and 406 women with irisin measurements were selected and a standardised symptom limited cardiopulmonary exercise test was used. Exercise capacity was quantified by oxygen uptake at anaerobic threshold (VO2@AT), peak exercise (peakVO2) and maximum power output at peak exertion. In addition, the oxygen pulse was assessed. ANOVA and multivariable linear regression analyses were performed stratified by sex and adjusted for age, weight, height and smoking. RESULTS: In men, we observed inverse associations between irisin serum concentration and exercise capacity assessed by peakVO2 and maximum power output. In contrast, in women a trend towards a positive relationship between irisin and peakVO2 was detected, whereas none of the other parameters showed significant associations with irisin. CONCLUSION: Based on a large population sample, our results did not confirm the previous reported positive linkage between exercise and irisin. Thus the relationship needs further investigation in particular with respect to sex differences.

ß-blocker therapy and heart rate control during exercise testing in the general population: role of a common G-protein ß-3 subunit variant.

AIM: Impaired heart rate (HR) response to exercise is associated with increased cardiovascular morbidity and mortality. We analyzed whether common variants (rs5443/C825T and rs5442/G814A) in the G-protein ß3 subunit (GNB3) gene modulate interindividual variation in ß-blocker responses with respect to HR. MATERIALS & METHODS: Among 1614 subjects (347 current ß-blocker users) of a population-based study, HR during symptom-limited exercise testing was analyzed by multilevel linear regression models adjusted for potential confounders. RESULTS: In ß-blocker users, but not in nonusers, HR was attenuated in rs5443 T allele carriers (TC/TT vs CC) with lower adjusted HR over the entire exercise period from rest to peak workload (3.5 bpm; 95% CI: 1.1-5.8; p < 0.01), and during recovery (4.2 bpm; 95% CI: 0.6-7.8; p = 0.02). The genotype-related HR reducing effect at peak exercise varied by up to 7.5 bpm (CC vs TT), more than a third (35.9%) of the total ß-blocker effect (20.9 bpm). By contrast, rs5442 had no impact on any HR-related parameter. CONCLUSION: In this population-based sample, a common GNB3 polymorphism (C825T) was significantly related with response to ß-blocker therapy with respect to HR during exercise and HR recovery, respectively. Further prospective studies are needed to confirm these associations and to examine their potential clinical relevance.

Are serum thyrotropin levels within the reference range associated with endothelial function?

AIMS: High serum thyrotropin (TSH) levels within the reference range might be associated with an increased cardiovascular risk. In the present study, we investigated the association between serum TSH levels and flow-mediated dilation (FMD) as a measure of endothelial dysfunction. METHODS AND RESULTS: The study population comprised 1364 subjects (670 women) aged 25-85 years with serum TSH levels between 0.25 and 2.12 mIU/L recruited from 5-year follow-up of the Study of Health in Pomerania. No interventions were performed. Measurements of FMD and nitrate-mediated dilation (NMD) were performed in the supine position using standardized ultrasound techniques. FMD and NMD values below the median of each distribution were considered decreased. Analyses adjusted for age, sex, smoking, and systolic and diastolic blood pressure revealed a non-significant inverse trend between serum TSH levels and FMD (P = 0.130). Subjects with serum TSH levels above the highest quartile had lower median FMD values relative to subjects with serum TSH levels below the lowest quartile (4.86 vs. 5.43%, P < 0.05). A linear inverse trend between serum TSH levels and decreased FMD barely missed statistical significance (P = 0.138). Subjects with high serum TSH levels had higher odds of decreased FMD relative to subjects with low serum TSH levels (odds ratio 1.42; 95% confidence interval 1.02; 1.96; P < 0.05). These associations were more pronounced in men than in women. There were no such associations for NMD. CONCLUSION: Serum TSH levels within the upper reference range are associated with impaired endothelial function. Our findings contribute to the discussion on whether the upper TSH reference limit should be redefined.

Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption.

OBJECTIVES: The objective of this study was to investigate whether immunoadsorption (IA) removes cardiodepressant antibodies from the plasma of patients with dilated cardiomyopathy (DCM), as well as to describe their effects on isolated rat cardiomyocytes. BACKGROUND: Immunoadsorption induces early hemodynamic improvement in patients with DCM. The mechanisms for this improvement remain to be elucidated. METHODS: Patients with DCM (n = 11; left ventricular ejection fraction < 30%, cardiac index [CI] < 2.5 l/min per m(2)) were treated with IA on three consecutive days, with one IA session daily, by application of specific antibody columns directed against human immunoglobulin (Ig). Immunoadsorption was also conducted on 500 ml of blood taken from nine healthy donors (control subjects). After passage of plasma, the IA columns were regenerated. Column eluent (CE) was collected and dialyzed (100 kD). Confocal laser scanning microscopy was used to analyze the effects of CE on cell contraction and on Ca(2+)-dependent fluorescence in isolated, field-stimulated adult rat cardiomyocytes loaded with cell-permeable Fluo-3. Immunoprecipitation with different preparations of myocardial protein fractions was used for characterization of cardiotropic antibodies. RESULTS: During IA, the IgG plasma level decreased from 10.7 +/- 0.6 to 2.4 +/- 0.1 g/l (mean +/- SEM), and the CI increased from 2.2 +/- 0.1 to 2.7 +/- 0.2 l/min per m(2) (p < 0.01). The CE obtained from control subjects did not influence Ca(2+) transients or cell shortening of cardiomyocytes. In contrast, in patients with DCM, the CE collected during the first regeneration cycle of the first IA session caused an immediate and dose-related decrease of Ca(2+) transients (dilution 1:5; -22.7 +/- 5.5%; p < 0.01) and cell shortening (dilution 1:5; -29.9 +/- 6.0%, p < 0.01). Early hemodynamic improvement among the patients correlated with the cardiodepressant effect of CE on the isolated cardiomyocytes. Purification of CE by protein A adsorption indicated that the cardiodepressant substances are antibodies. Immunoprecipitation revealed that the eliminated antibodies are capable of binding to various myocardial proteins. CONCLUSIONS: Cardiac autoantibodies play a functional role in DCM, and their removal may induce early hemodynamic improvement.