Prevalence of early repolarization syndrome and long-term clinical outcome in patients with the diagnosis of idiopathic ventricular fibrillation.

Idiopathic ventricular fibrillation (IVF) is diagnosed in up to 14% of sudden cardiac death (SCD) survivors. Early repolarization syndrome (ERS) in patients with ventricular tachyarrhythmia is characterized by an elevated J-point in inferior and/or antero-lateral leads. Our objectives were to determine the prevalence of ERS in IVF patients, and to evaluate potential differences in clinical outcome. Out of 3,552 implantable cardioverter defibrillator (ICD) carriers, 758 SCD survivors were retrospectively identified from the databases of the Medical Universities of Vienna and Innsbruck within the last three decades. Early repolarization pattern (ERP) was classified either as "notching" or "slurring". Endpoints were defined as appropriate ICD therapies for ventricular tachyarrhythmia, either anti-tachycardia pacing or shock, and all-cause mortality. After exclusion of recognized reasons for SCD, 50 patients were assigned to the diagnosis of IVF (6.6%). An ERP was identified in 10 patients, most of them with notching (n = 8). After a mean follow-up of 11.2 ± 6.7 years (539.3 patient years), appropriate ICD therapies were found in 50% of ERS and 43% of IVF patients without ERP (p = 0.732). In ERS patients, all ICD therapies were found in patients with notching pattern. Similarly, incidence of inappropriate ICD therapies, and all-cause mortality was comparable (30% vs. 23%, p = 0.707; 10% vs. 5%, p = 0.496, respectively). In 758 SCD survivors, we found a low prevalence of IVF and ERS. Similar event rates were reported concerning all-cause mortality and ICD therapies for ventricular tachyarrhythmia after long-term follow-up in this cohort.

Long-term physical activity leads to a significant increase in serum sRAGE levels: a sign of decreased AGE-mediated inflammation due to physical activity?

There is growing evidence that low levels of the circulating soluble receptor of advanced glycation end products (sRAGE) are a valuable predictor of cardiovascular disease (CVD). The aim of this prospective study was to investigate the influence of long-term physical activity on serum sRAGE levels. 109 subjects were recruited, and 98 completed the study. Participants were asked to perform exercise within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. sRAGE was measured at baseline and after 2/6/8 months by ELISA. Backwards, multiple linear regression analysis was performed to investigate the association of co-variables age, sex, BMI, and performance at baseline, HbA1c, and lipoprotein a with baseline sRAGE levels. We identified BMI and lipoprotein a as significant predictors for baseline sRAGE levels. Compared to subjects with a performance gain ≤ 4.9% subjects with a gain > 5% showed a significant increase in sRAGE levels up to 22%. sRAGE serum levels correlate negatively with lipoprotein a levels and BMI and long-term physical activity leads to a significant increase in serum sRAGE levels (9-22%), whereby the sRAGE increase is most pronounced in subjects with initially low-performance levels, suggesting that in particular, these subject profit the most from increased physical activity. The sport-mediated increase of sRAGE might be a sign of decreased AGE-mediated inflammation and highlight the protective effect of sports on CVD and other disease which are at least partly mediated by an increased inflammation status.Clinical trials registration NCT02097199.

Endurance training significantly increases serum endocan but not osteoprotegerin levels: a prospective observational study.

BACKGROUND: Endocan (EN) was suggested a potential inflammatory and cardiovascular disease (CVD) marker which might also be involved in renal failure and/or renal failure-associated vascular events. It is not clear whether osteoprotegerin (OPG) is a pro- or anti-atherogenic factor, however, it is agreed upon that OPG is elevated in subjects with increased calcification status. The aim of the study was to investigate the influence of long-term physical activity on serum endocan (EN) and osteoprotegerin-levels. METHODS: One hundred nine subjects were told to increase their amount of physical activity for 8 months by performing 150min/week moderate or 75min/week vigorous exercise. Incremental cycle ergometer tests were performed at the beginning and the end of the study to prove and quantify the performance gain. Blood samples were drawn at baseline and every 2 months for the determination of EN and OPG. To investigate the difference between baseline and 8 months levels of EN and OPG we used a paired sample t-test. To investigate the significance of the tendency of the progression (baseline/2 months/4 months/6 months/8 months) we used a Friedman test. RESULTS: Thirty-eight female and 60 male subjects completed the study. In the group of 61 subjects who had a performance gain by >4,9% EN-levels increased from 146 ± 110 to 196 ± 238 pg/ml (p = 0,036) equivalent to an increase of 33,5% but there was no significant change in OPG (4,4 ± 2,4 pmol/l vs. 4,3 ± 2,1 pmol/l; p = 0,668). CONCLUSIONS: Physical activity increases significantly EN-levels relativizing the status of EN as proinflammatory factor. EN should rather be considered as a mediator which is involved in several physiological (e.g., angiogenesis) but also pathological processes (e.g., CVD, tumour progression or endothelium-dependent inflammation) and whose expression can be significantly influenced by long term endurance training. TRIAL REGISTRATION: Clinical trial registration number: NCT02097199 Date of trial registration at Clinical Trials.gov: 24.03.2014; last update: 6.1.2016.

Sports and HDL-Quality Reflected By Serum Amyloid A and Surfactant Protein B.

Background: The aim of this prospective study was to investigate the influence of long-term physical activity on HDL quality, reflected by serum amyloid A (SAA) and surfactant protein B (SPB). Methods and results: 109 healthy subjects were recruited, 98 completed the study. Participants perform within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. SAA and SPB were measured at baseline and after 4 and 8 months by ELISA. In contrary to HDL-quantity, there was no sports-induced change in SAA or SPB observable. However, significant predictors for SPB-levels were smoking status, BMI and weekly alcohol consumption and for SAA weekly alcohol consumption together with sex and hsCRP-levels. Conclusions: Long-term physical activity increases HDL-quantity but has no impact on HDL-quality reflected by SAA and SPB. Smoking is associated with higher SPB-levels and the weekly alcohol intake is associated with both higher SAA and SPB-levels suggesting a damaging effect of smoking and drinking alcohol on the HDL-quality. We assume that HDL-quality is at least as important as HDL-quantity when investigating the role of HDL in (cardiovascular) disease and should receive attention in further studies dealing with HDL.

Long-term endurance training increases serum cathepsin S and decreases IL-6 and hsCRP levels.

Cathepsin S (CS) was shown to play a key role in cancer progression, atherosclerosis, heart valve disease, insulin resistance and diabetes mellitus. The present prospective study aimed to investigate the influence of sports on CS, interleukin-6 (Il-6) and high-sensitivity C-reactive protein (hsCRP) levels. Ninety-eight of 109 participants completed the study. Ergometries were performed at baseline and after 8 months to evaluate/quantify the performance gain. Blood samples were taken at baseline and every 2 months. CS was measured by ELISA (enzyme-linked immunosorbent assay). Compared to the control group (mean performance gain -3.41 ± 4.62%) we observed a significant physical-activity-induced increase of CS levels (3.45-3.73 ng · ml-1; P = 0.027) and a significant decrease of Il-6 (2.43-1.91 pg · ml-1; P = 0.031) and hsCRP-levels (0.11-0.09 mg · dl-1; P = 0.001) in the intervention group (mean performance gain: 12.13 ± 6.32%). Furthermore, the tendency of the progression was significant for CS and Il-6 (P = 0.002/0.033). We could show a significant sports-induced decrease of the classic inflammation parameters hsCRP/Il-6, probably expressing a downregulation of permanently prevalent inflammation processes. Simultaneously CS levels increased significantly. Our results show that increasing CS amounts are not simply to equal with an enhanced inflammation status and might even have beneficial effects on inflammation and angiogenesis.

Osteopontin is elevated in patients with mitral annulus calcification independent from classic cardiovascular risk factors.

BACKGROUND: Osteopontin (OPN) regulates the Ca(++)-deposition in bone and coronary arteries. Elevated OPN were also associated with (aortic) valve calcification in healthy individuals. This study aimed to investigate the association between OPN levels and mitral annulus calcification (MAC) in patients with coronary artery disease (CAD). METHODS: In this cross-sectional study OPN-levels were measured in 223 non-or ex-smoking patients (160 male, mean age: 61,09 ± 11,02 years; 63 female: mean age: 67,49 ± 7,87 years) with CAD. Plasma OPN levels were measured by ELISA and MAC was evaluated by echocardiography. RESULTS: Forward stepwise logistic regression analysis (likelihood quotient) showed significantly higher OPN-levels in patients with MAC compared to patient without calcified mitral annulus independent from the classic risk factors age and severity of coronary artery disease (CAD). In addition to age and the severity of CAD, the circulating OPN amount was a significant predictor for MAC. CONCLUSIONS: This is the first clinical trial which observed increased circulating OPN levels in MAC, suggesting a distinct role of OPN in the process of MAC. Considering the current knowledge about OPN it is more likely that OPN does not promote but counteracts valve calcification and therefore is elevated in course of a calcification processes.

Physical inactivity increases endostatin and osteopontin in patients with coronary artery disease.

The balance between the angiostatic factor endostatin (ES) and angiogenic factor osteopontin (OPN) is essential in physiological and pathological angiogenesis. Several circumstances might influence this equilibrium and are of distinct interest when investigating mechanisms in coronary artery disease (CAD). The present explorative cross-sectional study was to investigate the influence of physical inactivity on ES and OPN levels in 181 male and 71 female patients with angiographycally verified CAD. Anamnestic and laboratory data were collected; ES was measured in serum and OPN in plasma by ELISA. Univariate analysis of variance was used to test for the influence of physical activity on ES and OPN levels and age, BMI, sex and diabetes status were included as covariates. ES and OPN intercorrelated significantly (r = 0.42; p < 0.001). ES and OPN decreased significantly in response to increasing activity level of patients suffering CAD (F = 5.5; p < 0.001 and F = 3.6; p < 0.01 resp.). This study is the first to show a linear decrease in ES and OPN levels in CAD patients depending on the degree of physical activity undergone. Lower levels of ES and OPN in physically active patients might be a sign of increased angiogenesis and decreased inflammation and calcifying activity and therefore contribute to the understanding of the damaging effect of physical inactivity in cardiovascular disease.

Exercise increases serum endostatin levels in female and male patients with diabetes and controls.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is often associated with atherosclerotic changes in coronary vessels, most notably plaques. The angiostatic parameter endostatin is able to inhibit angiogenesis in tissue as well as in plaques and therefore plays an important role in physiological and pathological neovascularisation. The aim of the present study was to investigate sex-specific differences and the influence of exercise on circulating endostatin levels in patients suffering from diabetes, and control subjects. METHODS: In total, 42 T2DM-patients and 45 control subjects were investigated. They underwent a graded physical stress test (ergometry). Serum endostatin levels were measured in venous blood at rest and directly after reaching maximum workload. RESULTS: Females showed significantly higher endostatin levels at baseline measurements compared to men, independently of their underlying disease. In both female and male T2DM-patients endostatin levels were significantly lower compared to controls. Both groups and sexes showed a significant increase of endostatin after physical stress, whereas the extent of endostatin-increase was between 10.59-15.05%. CONCLUSION: Middle-aged healthy female individuals as well as female T2DM-patients showed higher circulating serum endostatin levels compared to males, suggesting a hormonal influence on baseline circulating endostatin amounts. Exercise-induced increase in endostatin is also observable in patients suffering from T2DM. Concerning vascularisation, lower endostatin levels in T2DM might be advantageous. Concerning plaque stability, lower levels might be prejudicial. TRIAL REGISTRATION: Clinical Trial Registration-URL: http://clinicaltrials.gov/ct2/results?term=NCT01165515.

New ECG algorithms with improved accuracy for prediction of culprit vessel in inferior ST-segment elevation myocardial infarction.

BACKGROUND: In addition to diagnosing acute myocardial infarction (MI), the electrocardiogram (ECG) may also predict the culprit coronary artery. We aimed to assess the diagnostic accuracy of ECG algorithms predicting the occluded vessel in inferior ST-segment elevation myocardial infarction (STEMI). METHODS: This retrospective cohort study included 300 consecutive patients with inferior STEMI undergoing acute coronary angiography. A new method based on the summation of ST-segment deviations in multiple leads from the first 12-lead-ECG was used to develop algorithms to discriminate between right coronary artery (RCA) and circumflex artery (CX) occlusion. Additionally, older algorithms were reassessed. RESULTS: The RCA was occluded in 235 patients (78%) and the CX in 65 (22%). ST-segment deviations differed significantly between RCA and CX occlusions in leads I, III, aVR, aVL, aVF and V1. ST-segment deviations in lead I showed the highest discriminatory ability of a single lead (area under the receiver operating curve [AUC]=0.77). The summation of multiple leads further increased the discriminatory ability ("III-II+aVF+aVR+V1:" AUC=0.86; "III-II-I+aVF+V1:" AUC=0.85). The best binary algorithm "III-II-I+aVF+V1>0.1 mV" classified 86% of cases correctly and was better than the best old algorithm (83.3%). The simpler algorithm "III+aVR+V1≥0.1 mV" still predicted 85.0% correctly. All algorithms had higher sensitivities for RCA than for CX detection and performed better in right-dominant anatomy. CONCLUSIONS: A new approach summating multiple ST-segment deviations generated ECG algorithms with higher diagnostic accuracy to predict the occluded vessel in inferior STEMI compared to previous studies. These algorithms may facilitate earlier risk stratification for patients at risk of postinfarct complications.

Long-term physical activity modulates adipsin and ANGPTL4 serum levels, a potential link to exercise-induced metabolic changes.

BACKGROUND: Within the presented prospective study, we aimed to illuminate the effect of long-term physical exercise on serum levels of adipsin (complement factor D) and angiopoietin-like 4 (ANGPTL4). Although past studies already outlined the effects of acute exercise, our trial design aimed to depict the development under long-term physical activity conditions. METHODS: Ninety-eight participants were included in the study and were asked to perform eight months of moderate physical activity for at least 150 minutes/week and/or vigorous-intensity exercise for at least 75 minutes/week. According to initial performance and performance gain throughout the study period, four groups were formed and subsequently compared. Blood sampling for the determination of routine laboratory parameters was done at baseline, after 2, 6, and 8 months. Additionally, adipsin and ANGPTL4 serum levels were concurrently quantified using commercially available ELISA kits. RESULTS: The study cohort consisted of 61.2% male participants with an average age of 49.3±6.7 years. Adipsin and ANGPTL4 were found to be strongly increased by long-term physical exercise. Participants displaying a performance gain of >2.9% throughout the study showed significantly increased serum levels of both biomarkers. CONCLUSIONS: Serum levels of adipsin and ANGPTL4 were closely tied to the individual performance gain of the participating probands. An association of adipsin levels, initial performance, and serum triglycerides was found at baseline. Interestingly, this interrelationship was not detectable after eight months of physical training. This finding might indicate adipsin's involvement in linking triglyceride-balance to individual performance and energy demands in a homeostatic state.

Obesity and its influence on liver dysfunction, morbidity and mortality after liver resection.

Background: Obesity and associated steatosis is an increasing health problem worldwide. Its influence on post-hepatectomy liver failure (PHLF) and after liver resection (LR) is still unclear. Methods: Patients who underwent LR were investigated and divided into three groups [normal weight: body mass index (BMI) 18.5-24.9 kg/m2, overweight: BMI 25.0-29.9 kg/m2, obese: BMI ≥30 kg/m2] in this retrospective study. Primary aim of this study was to assess the influence of BMI and nonalcoholic steatohepatitis (NASH) on PHLF and morbidity. Results: Of 888 included patients, 361 (40.7%) had normal weight, 360 (40.5%) were overweight, 167 (18.8%) were obese. Median age was 62.5 years (IQR, 54-69 years). The primary indication for LR was colorectal liver metastases (CLM) (n=366, 41.2%). NASH was present in 58 (16.1%) of normal weight, 84 (23.3%) of overweight and 69 (41.3%) of obese patients (P<0.001). PHLF occurred in 16.3% in normal weight, 15.3% in overweight and 11.4% in obese patients (P=0.32). NASH was not associated with PHLF. There was no association between patients' weight and the occurrence of postoperative complications (P=0.45). At multivariable analysis, solely major LR [odds ratio (OR): 2.7, 95% confidence interval (CI): 1.83-4.04; P<0.001] remained a significant predictor for PHLF. Conclusions: Postoperative complications and PHLF are comparable in normal weight, overweight and obese patients and LRs using modern techniques can be safely performed in these patients.

Right Atrial Phasic Function in Heart Failure with Preserved Ejection Fraction: Cardiac Magnetic Resonance Feature Tracking and Outcomes.

BACKGROUND: This study sought to investigate the prognostic impact of right atrial (RA) size and function in patients with heart failure with preserved ejection fraction (HFpEF) in sinus rhythm (SR) and atrial fibrillation (AF). METHODS: Consecutive HFpEF patients were enrolled and indexed RA volumes and emptying fractions (RA-EF) were assessed by cardiac magnetic resonance imaging (CMR). For patients in SR, feature tracking of the RA wall was performed during CMR. In addition, all patients underwent right and left heart catheterization and 6 min walk distance (6MWD) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) evaluations. We prospectively followed patients and used Cox regression models to determine the association of RA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. RESULTS: A total of 188 patients (71% female patients, 70 ± 8 years old) were included. Ninety-two patients (49%) were in persistent AF. Eighty-five patients reached the combined endpoint during a follow-up of 69 (42-97) months. After a multivariate cox regression analysis, the impaired RA reservoir strain (HR 0.949; 95% CI [0.909-0.990], p = 0.016), the RA reservoir strain rate (HR 0.991; 95% CI [0.983-0.999], p = 0.028), the RA conduit strain (HR 0.932; 95% CI [0.879-0.988], p = 0.019), and the RA conduit strain rate (HR 0.989; 95% CI [0.881-0.997], p = 0.011) were significantly associated with a worse outcome for patients in SR. In persistent AF, no RA imaging parameter was related to outcome after a multivariate regression analysis. CONCLUSIONS: In HFpEF patients in SR, CMR parameters of impaired RA conduit and reservoir function are associated with dismal cardiovascular outcomes. In persistent AF, RA parameters lose their prognostic ability.

Risk stratification and long-term outcome of patients receiving in-hospital medical emergency team critical care: experience from Austria's largest medical center.

BACKGROUND: We aimed to investigate predictors for long-term survival of in-hospital patients with medical emergency team (MET) consultation with or without in-hospital cardiac arrest (IHCA) in Austria's largest medical center. METHODS: Data of patients, who needed an intervention of a MET between 01/2014 and 03/2020 were reviewed for this retrospective analysis. RESULTS: In total, 708 MET calls were analyzed. The minimum follow-up was 7 months, the maximum 6.2 years. The main MET indications were circulatory failure (63%) followed by respiratory failure (27.1%), and bleeding events (3.5%). IHCA with subsequent cardiopulmonary resuscitation (CPR) was experienced by 425 (60%) patients. Of those, 274 (64%) reached return of spontaneous circulation (ROSC), and 221 (52%) survived the first 24-hours (median survival: 146 days) and 22.1% the first year. After adjustment for potential confounders, age (P<0.001), time to ROSC (P<0.001), a non-shockable rhythm (P=0.041), chronic kidney disease (CKD, P=0.041), peak lactate levels (P<0.001), and C-reactive protein (P=0.001) were associated with long-term all-cause mortality in IHCA patients in Cox regression analysis. The 283 MET calls (40%) which were due to other reasons than IHCA were associated with a much better 24-hours (93%) and 1-year survival (61.8%). Beside age (P<0.001), the main risk factors associated with mortality in MET patients without IHCA were comorbidities such as chronic obstructive pulmonary disease (COPD, P=0.008), CKD (P=0.001), pulmonary hypertension/chronic thromboembolic pulmonary hypertension (PH/CTEPH, P=0.024), and cancer (P=0.040). CONCLUSIONS: Patients triggering MET calls have an increased mortality, especially those with IHCA. Predictors of mortality comprise age, comorbidities, and cardiac arrest-related parameters. A better characterization of MET call populations and their outcome might help to improve clinical decision making.

RANTES and CD40L under Conditions of Long-Term Physical Exercise: A Potential Link to Adaptive Immunity.

Regular physical exercise was found to be associated with an improved immune response in previous studies. RANTES and CD40L play a pivotal role in host defense, and individuals lacking adequate expression are prone to virus and opportunistic infections. A total of 98 participants were enrolled in this study. The probands were asked to perform moderate physical activity, and bicycle stress tests were performed at the baseline and after 8 months of training to evaluate individual performance. RANTES and CD40L were found to be increased by long-term physical exercise. In particular, probands with a performance gain of ≥3% displayed a pronounced elevation of both markers, paired with a decrease in circulating IL6 levels and an improved lipid profile. In summary, we were able to highlight rising levels of serum RANTES and CD40L under the conditions of physical exercise. Taking their role in host defense into account, a conjunction of physical activity and the adaptive immune system could therefore be assumed. Furthermore, low inflammatory profiles in probands with a significant performance gain suggest a modulation through exercise rather than a generalized pro-inflammatory status.

Physical Exercise Promotes DNase Activity Enhancing the Capacity to Degrade Neutrophil Extracellular Traps.

(1) Background: An unhealthy lifestyle is a significant contributor to the development of chronic diseases. Physical activity can benefit primary and secondary prevention. Higher DNase activity is associated with favourable outcomes after cardiovascular (CV) events. In this study, we aimed to investigate the influence of consequent endurance exercise on DNase activity. (2) Methods: 98 subjects with at least one CV risk factor but the physical ability to perform endurance training were included. Individuals performed a bicycle stress test at the beginning and after 8 months to assess physical performance. In between, all participants were instructed to engage in guideline-directed physical activity. Blood samples were drawn in two-month intervals to assess routine laboratory parameters, cell-free DNA (cfDNA), and DNase activity. (3) Results: Prevailing CV risk factors were overweight (65.9%), a positive family history (44.9%), hypertension (32.7%) and smoking (20.4%). Performance changed by 7.8 ± 9.1% after 8 months. Comparison of baseline to 8 months revealed a decrease in cfDNA and an increase in DNase activity. This effect was driven by participants who achieved a performance gain. (4) Conclusions: Regular physical activity might improve CV health by increasing DNase activity and thereby, the capacity to lower pro-inflammatory signalling, complementing measures of primary and secondary prevention.

Regular Training Increases sTWEAK and Its Decoy Receptor sCD163-Does Training Trigger the sTWEAK/sCD163-Axis to Induce an Anti-Inflammatory Effect?

BACKGROUND: Low levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) were reported in patients with coronary artery disease, heart failure, chronic kidney disease and diabetes mellitus. Soluble cluster differentiation 163 (sCD163) serum levels are related to M2 macrophages, having anti-inflammatory attributes. As sport is well-known for its anti-inflammatory and cardioprotective effects we aimed to investigate the influence of eight months of physical activity on serum sCD163 and sTWEAK levels. METHODS: In total, 109 subjects with at least one cardiovascular risk factor were asked to perform endurance training within the calculated training pulse for eight months. Overall, 98 finished the study. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. The cohort was divided into four groups, dependent on their baseline performance and performance gain. sCD163 and sTWEAK were measured at baseline and after two, six and eight months by ELISA. RESULTS: Those participants who had a performance gain of ≤2.9% (mean gain 12%) within eight months showed a significant increase in sTWEAK (group 2: from 133 to 200 pg/mL, p = 0.002 and group 4: from 166 to 212 pg/mL, p = 0.031) and sCD163 levels (group 2: from 255 to 348 ng/mL, p = 0.035 and group 4: from 247 to 288 ng/mL, p = 0.025) in contrast to subjects without performance gain (sTWEAK: group 1: from 161 to 177 pg/mL, p = 0.953 and group 3: from 153 to 176 pg/mL, p = 0.744; sCD163: group 1: from 289 to 256 ng/mL, p = 0.374 and group 4: from 291 to 271 ng/mL, p = 0.913). Baseline sCD163 correlated with erythrocyte count, hematocrit, ASAT and lipoprotein a, the presence of hypertension and a BMI > 30 kg/m2. CONCLUSION: Regular physical activity leads to a significant increase in sCD163 and sTWEAK levels of up to 37% and 50%, respectively. It is well-known that physical activity prevents or retards the onset and genesis of chronic inflammatory disease. One possible way of how training evolves its beneficial effect might be by modifying the inflammation status using the sTWEAK-sCD163 axis. Brief Summary: Regular physical activity leads to a significant increase in sTWEAK and sCD163 levels. Both factors are diminished in patients with chronic (inflammation-based) diseases, such as coronary artery disease, heart failure, pulmonary artery hypertension, chronic kidney disease and diabetes mellitus. It seems that the amounts of soluble TWEAK and CD163 are essential for a healthy balance and modulation between pro- and anti-inflammatory processes, and regular physical training could use the sCD163-sTWEAK axis to unfold its beneficial effect.

Novel cardiovascular biomarkers in patients with cardiovascular diseases undergoing intensive physical exercise.

BACKGROUND: In this trial, we analyzed the plasma levels of novel biomarkers that reflect different pathophysiological pathways (sST2: mechanical strain, IGF-BP2: metabolic pathways, suPAR and GDF-15: inflammatory processes) in patients undergoing physical exercise to investigate the effects of training on their plasma concentrations. METHODS: Plasma concentrations of novel biomarkers (sST2, IGF-BP2, suPAR and GDF-15) were analyzed by means of ELISA in patients with stable coronary artery disease (CAD) undergoing four weeks of high- and moderate-intensity training (EXCITE Trial) and in patients with one or more cardiovascular risk factors undergoing eight months of intensive physical exercise (IGF-BP2). Plasma levels of sST2 in patients undergoing eight months of intensive exercise have been published previously by our study group (1.13-fold change, P=0.045). RESULTS: Four weeks of high-intensity exercise training resulted in a statistically significant change in the plasma level of sST2 (1.106-fold change, P=0.0054) and IGF-BP2 (1.24-fold-change, P=0.0165). Eight months of intensive exercise resulted in a significant increase of IGF-BP2 (median 61.2 ng/mL to 80.7 ng/mL, 1.319-fold change, P=0.006). CONCLUSIONS: The significant increase of sST2 after four weeks might be a short-term effect due to the mechanical strain caused by the high-intensity training program, whereas the increase in IGF-BP2 after four weeks and eight months is likely a result of metabolic changes due to physical exercise.

Paper-based training diaries for monitoring of performance progress due to long-term physical activity.

INTRODUCTION: Training diaries are a common tool for training monitoring; however, their correlation with an effective performance gain is unclear. OBJECTIVES: The aim of this prospective study was to investigate whether monitoring of training by paper­based training diaries reflects the training progress measured by a bicycle stress test in hobby athletes. PATIENTS AND METHODS: Out of 109 hobby athletes who were instructed to work out for 8 months with a calculated training pulse, 98 participants completed the study. Training workload (intensity and time) was recorded with special training diaries. To assess the objective performance gain or change, the bicycle stress test was performed at baseline and at the end of the study. Surrogate parameters associated with increased physical activity were also recorded. RESULTS: Participants who had a performance gain of at least 3% (mean gain of about 12%) in the bicycle stress test worked out between 547 and 576 min/mo with moderate intensity, and between 14 and 187 min/mo with high intensity. Neither moderate- nor high-intensity training correlated with the performance gain. CONCLUSIONS: Paper-based training diaries might serve as an additional tool in the monitoring of training progress. However, because of the discrepancy between reported training loads and objectively measured training progress, they are not suitable to replace a standard bicycle stress test for an exact determination of performance gain in hobby athletes. New devices, such as fitness trackers or watches, may present better alternatives in the future.

Serum heart-type fatty acid-binding protein decreases and soluble isoform of suppression of tumorigenicity 2 increases significantly by long-term physical activity.

The aim of this prospective study was to investigate the influence of long-term physical activity on biomarkers for myocyte ischemia (heart-type fatty acid-binding protein, H-FABP), matrix remodelling/vascular stress (soluble isoform of suppression of tumorigenicity 2, sST2) and inflammation (soluble urokinase-type plasminogen activator receptor, suPAR). In this prospective observational study 109 subjects were recruited, 98 completed the study. Subjects were asked to perform exercise within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. Twenty-seven subjects with a performance gain <2.9% were excluded. suPAR, H-FABP and sST2 were measured in serum at baseline and after 2, 4 and 8 months by ELISA. We found a significant decrease in H-FABP (1.86 (0.86) to 1.29 (0.98) ng/mL; p<0.01) and a significant increase in sST2 levels (6126 (2759) to 6919 (3720) pg/mL; p=0.045) during the observation period of 8 months while there was no remarkable change in suPAR levels. We interpret the activity-induced decrease in H-FABP as sign of lower subclinical myocardial ischemia and better perfusion, probably due to a more economic metabolization and electrolyte balance. The increase in sST2 might reflect physiological sports-induced vascular stress. As H-FABP and sST2 play an important role in the pathomechanism of ischemic cardiomyopathy (iCMP) further studies should investigate the influence of regular physical activity on these biomarkers in a population of patients with iCMP. TRIAL REGISTRATION NUMBER: NCT02097199.

New Cardiovascular Biomarkers in Ischemic Heart Disease-GDF-15, A Probable Predictor for Ejection Fraction.

BACKGROUND: Various biomarkers have been associated with coronary artery disease (CAD) and ischemic heart failure. The aim of this study was to investigate the correlation of serum levels of soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), and soluble suppression of tumorigenicity 2 (sST2) with left ventricular ejection fraction (EF) in CAD patients and controls. METHODS AND RESULTS: CAD patients were divided into three groups according to their EF as measured by the biplane Simpson method (53-84%, 31-52%, ≤30%). Overall, 361 subjects were analyzed. In total, 155 CAD patients had an EF of 53-84%, 71 patients had an EF of 31-52%, and 23 patients had an EF of ≤30% as compared to 112 healthy controls (age 51.3 ± 9.0 years, 44.6% female). Mean ages according to EF were 62.1 ± 10.9, 65.2 ± 10.1, and 66.6 ± 8.2 years, respectively, with females representing 29.0, 29.6, and 13.0%. suPAR, GDF-15, H-FABP, and sST2 values were significantly higher in CAD patients and showed an exponential increase with decreasing EF. In a multiple logistic regression model, GDF-15 (p = 0.009), and NT-brain natriuretic peptide (p = 0.003) were independently associated with EF. CONCLUSION: Biomarkers such as suPAR, GDF-15, H-FABP, and sST2 are increased in CAD patients, especially in highly impaired EF. Besides NT-proBNP as a well-known marker for risk prediction, GDF-15 may be an additional tool for diagnosis and clinical follow-up.