The one-minute sit-to-stand-test performance is associated with health-related quality of life in patients with pulmonary hypertension.

INTRODUCTION: Patients with pulmonary hypertension (PH) have an impaired functional capacity and poor health-related quality of life (HRQoL). The one-minute sit-to-stand test (1-min STST) can be used for the assessment of functional capacity. AIMS: Our aim was to evaluate the 1-min STST performance and its association with patient-reported HRQoL in patients with PH. METHODS: We prospectively assessed functional capacity in 98 PH patients (mean age 66 ± 15 years, 55% female) using the 1-min STST. Patients had to stand up and sit down from a chair as many times as possible within one minute. Patients' HRQoL was evaluated with the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaire, which consists of the three subcategories symptoms, activities and quality of life (QoL). RESULTS: We observed a significant correlation of the 1-min STST performance with all HRQoL subcategories assessed with the CAMPHOR questionnaire: A lower number of 1-min STST repetitions correlated with more symptoms (rs = -.398, p < .001), worse functioning (rs = -.551, p < .001) and a decreased QoL (rs = -.407, p < .001). Furthermore, in the multivariable linear regression analysis, adjusted for age, sex, body mass index (BMI) and mean pulmonary artery pressure (mPAP), lower 1-min STST performance was an independent predictor for worse symptoms (est. ß = -0.112, p = .003), activities (est. ß = -0.198, p < .001) and QoL (est. ß = -0.130, p < .001) assessed with the CAMPHOR questionnaire. CONCLUSION: Our results indicate that regardless of age, sex, BMI and mPAP the 1-min STST performance is associated with all CAMPHOR HRQoL subcategories in patients with PH. Therefore, the 1-min STST performance might be a new option to assess functional capacity correlated to HRQoL in patients with PH.

Effects of cardiovascular risk factors and pre-existing diseases on the short-term outcome of Takotsubo syndrome.

BACKGROUND: The effects of cardiovascular risk factors (CVRF) on the development of most acute cardiac conditions are well established; however, little is known about the frequency and effects of CVRF in Takotsubo syndrome (TTS) patients. OBJECTIVE: The aim of our study was to compare the frequency of CVRF and pre-existing diseases (PD) of TTS patients to ST-elevation myocardial infarction (STEMI) patients and analyze their effects on short-term outcome. METHODS: We analyzed the frequency of CVRF (hypertension, hyperlipidemia, type II diabetes mellitus, smoking, chronic kidney disease, family history) as well as somatic and psychiatric PD at admission in TTS patients and compared them with STEMI patients. Their effect on short-term outcome was calculated using a combined endpoint of cardiogenic shock, cardiopulmonary resuscitation, mechanical ventilation, and/or in-hospital death. RESULTS: In total, 150 TTS and 155 STEMI patients were included in our study. We observed a higher frequency of psychiatric (30% vs. 7%, p < 0.001), neurological (5% vs. 0%, p = 0.01), and pulmonary (18% vs. 5%, p < 0.001) PD in TTS patients as compared to STEMI patients. There were less smokers (47% vs. 61%, p = 0.03) and patients with hyperlipidemia (24% vs. 51%, p < 0.001) in the TTS cohort than in the STEMI cohort. None of the CVRF or PD behaved as an independent predictor for adverse short-term outcome in TTS patients. CONCLUSION: Psychiatric, neurological, and pulmonary pre-existing diseases are more common in TTS than in STEMI patients. Interestingly, PD and CVRF do not seem to have any impact on the short-term outcome of TTS patients.

Functional capacity testing in patients with pulmonary hypertension (PH) using the one-minute sit-to-stand test (1-min STST).

BACKGROUND: The one-minute sit-to-stand-test (1-min STST) is a quick, space saving test to evaluate functional capacity. Exercise testing plays an important role in the long-term follow-up of pulmonary hypertension (PH) patients and is currently evaluated using the six-minute-walk-test (6MWT). The aim of the study was to assess the convergent validity of the 1-min STST in patients with PH and its association with markers of PH severity. METHODS: We evaluated 106 PH patients with the 1-min-STST and 6MWT and measured cardiorespiratory parameters (heart rate, blood pressure, oxygen saturation) before and after test conduction. N-terminal pro brain-type natriuretic peptide (NT-proBNP), WHO functional class (WHO-FC) and mean pulmonary artery pressure (mPAP) were defined as markers of PH severity. RESULTS: Strong correlation was found between performances of 1-min STST and 6MWT (r = .711, p < .001), indicating convergent validity. Both tests were inversely associated with NT-proBNP (STST: r = -.405, p < .001; 6MWT: r = -.358, p < .001), WHO-FC (STST: r = -.591, p < .001; 6MWT: r = -.643, p < .001) and mPAP (STST: r = -.280, p < .001; 6MWT: r = -.250, p < .001). Significant changes in cardiorespiratory parameters were observed in both tests (all p < 0.001). Further the post-exercise cardiorespiratory parameters correlated strongly between the 1-min STST and 6MWT (all r ≥ .651, all p < .001). CONCLUSION: The 1-min STST demonstrated good convergent validity with the 6MWT and was associated with markers of PH severity. Furthermore, both exercise tests caused similar cardiorespiratory responses.

Antibiotic prescription after tooth extraction in adults: a retrospective cohort study in Austria.

BACKGROUND: Broad spectrum antibiotics are often used for the prophylaxis of infectious endocarditis and treatment of odontogenic infections, but there are limited data related to antibiotic use and adherence to prescription guidelines.  METHODS: Data from patients with tooth extraction between 2014 and 2018 were selected from a database of a regional health insurance fund. We created three data sets, one based on all tooth extractions, one on multiple teeth extractions, and one including only single tooth extraction. After data collection, descriptive analysis was carried out. The differences in prescription pattern of antibiotic medicine were tested by χ2 test, Student´s t-test or ANOVA. RESULTS: From 43,863 patients with tooth extraction, 53% were female, and 3,983 patients (9.1%) filled a prescription for antibiotic medicine. From 43,863 patients, 157 patients (0.4%) had endocarditis risk, but only 8 patients of these (5.1%) filled an antibiotic prescription. In total, 9,234 patients had multiple and 34,437 patients had only one tooth extraction. Patients with more than one tooth extraction received more often antibiotic treatment (10.7%) compared to those with single tooth extractions (χ2 = 36; p < 0,001). Patients with more than one tooth extraction were older, however, younger patients received antibiotics more frequently (t = 28,774, p = 0.001). There was no relationship with endocarditis risk status. Clindamycin and amoxicillin/clavulanic acid were the most frequently prescribed antibiotic medicines. CONCLUSIONS: In this retrospective cohort study, dentists did not discriminate prophylactic antibiotic prescription with regard to endocarditis risk status. A factor influencing prescribing behaviour of antibiotic medicines was the number of extracted teeth.

Exercise capacity assessed with the one-minute sit-to-stand test (1-min STST) and echocardiographic findings in patients with heart failure with preserved ejection fraction (HFpEF).

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality. Precise risk stratification remains challenging. The one-minute sit-to-stand-test (1-min STST), a quick, objective test of functional capacity may be helpful for stratification of clinical profile in HFpEF patients. OBJECTIVE: The aim of this initial investigation was to prospectively examine whether the 1-min STST can be used for the evaluation of exercise capacity in HFpEF patients and whether it is in line with echocardiographic as well as quality of life (QoL) findings. METHODS: 39 HFpEF patients were prospectively studied. Functional performance was examined with the 1-min STST and QoL with the CAMPHOR questionnaire. Clinical parameters including echocardiographic measurements [estimated pulmonary artery systolic pressure (ePASP), tricuspid regurgitation velocity (TRV)] were obtained. Patients were divided into two groups based on their number of 1-min STST repetitions (Group I: ≤50% of predicted 1-min STST repetitions using the norm-reference values developed by Strassmann et al. for healthy people, N=24; Group II: >50% of predicted 1-min STST repetitions, N=15). RESULTS: Patients in group I with limited 1-min STST performance showed worse echocardiographic parameters [higher ePASP (p=0.038), higher TRV (p=0.018) and more reduced tricuspid annular plane systolic excursion (TAPSE) (p=0.001)], worse six-minute walk test (6MWT) (p<0.001) and worse QoL (p<0.001) compared to patients in group II. CONCLUSION: Our study shows potential usefulness of the 1-min STST as an evaluative tool for exercise capacity in HFpEF patients, because patients with worse 1-min STST performance have worse clinical parameters and QoL.

Cardiovascular risk and mortality in patients with hyperuricemia treated with febuxostat or allopurinol: a retrospective nation-wide cohort study in Austria 2014-2017.

Patients with hyperuricemia and gout are at an increased risk for cardiovascular (CV) disease. Inhibition of the xanthine oxidase with allopurinol or febuxostat have become the mainstay for urate lowering therapy. However, it has been suggested that febuxostat increases the risk for CV mortality as compared to allopurinol. The aim of this retrospective cohort study was to assess the CV risk among patients with febuxostat or allopurinol therapy. Patients who initiated urate lowering therapy with febuxostat or allopurinol between 2014 and 2017 were selected from the drug reimbursement database of the Austrian health insurances funds. The primary CV endpoint was a composite of angina pectoris, nonfatal myocardial infarction, nonfatal subarachnoid or cerebral hemorrhage, nonfatal ischemic stroke, or death from any cause. In total, 28.068 patients (62.1% male) with a mean age of 71 years were included. 7.767 initiated febuxostat treatment and 20.301 received allopurinol. The incidence rate per 100 patient-years of the composite primary endpoint was 448 (febuxostat) and 356 (allopurinol) with a corresponding adjusted hazard ratio (HR) of 0.58 (95% CI 0.53-0.63) for allopurinol vs. febuxostat initiators. Similar HR were found for secondary endpoints including all-cause mortality [0.61 (95% CI 0.55-0.68)] and separate analyses of cardiac events [0.48 (95% CI 0.38-0.61)] and ischemic stroke [0.47 (95% CI 0.36-0.61)]. Data from this Austrian population-based study suggests that febuxostat initiators are at an increased risk for nonfatal CV events or death from any cause as compared to those with allopurinol. This is consistent with CV concerns of other trials, which limited the broad therapeutic use of febuxostat.

Changes in Skin Barrier Function after Repeated Exposition to Phospholipid-Based Surfactants and Sodium Dodecyl Sulfate In Vivo and Corneocyte Surface Analysis by Atomic Force Microscopy.

(1) Background: The aim of the study was to evaluate the effect of pure lecithins in comparison to a conventional surfactant on skin in vivo. (2) Methods: Physiological skin parameters were evaluated at the beginning and the end of the study (day 1 and day 4) (n = 8, healthy forearm skin) with an Aquaflux®, skin-pH-Meter, Corneometer® and an Epsilon® sensor. Confocal Raman spectroscopy was employed to monitor natural moisturizing factor, urea and water content of the participants' skin. Tape strips of treated skin sites were taken and the collected corneocytes were subjected to atomic force microscopy. Circular nano objects were counted, and dermal texture indices were determined. (3) Results: Transepidermal water loss was increased, and skin hydration was decreased after treatment with SDS and LPC80. Natural moisturizing factor and urea concentrations within the outermost 10 µm of the stratum corneum were lower than after treatment with S75 or water. Dermal texture indices of skin treated with SDS were higher than skin treated with water (control). (4) Conclusions: Results suggest very good (S75) or good (LPC80) skin-tolerability of lecithin-based surfactants in comparison to SDS and encourage further investigation.

Dose-dependent naloxone-induced morphine withdrawal symptoms in opioid-dependent males-a double-blinded, randomized study.

AIMS: Oral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine-naloxone dose ratio for an abuse-deterrent oral opioid formulation. METHODS: In a randomized, double-blinded, 2 × 2 cross-over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.Eur. (75 mg; [morphine mono]) or morphine HCl Ph.Eur. and naloxone HCl Ph.Eur. at ratios of 100:1 (75 mg: 0.75 mg; [morphine-naloxone 100:1]) or 200:1 (75 mg: 0.375 mg; [morphine-naloxone 200:1]). Acute naloxone-induced opioid withdrawal was evaluated using subjective (Short Opiate Withdrawal Scale-German [SOWS-G]) and observer-rated (Objective Opiate Withdrawal Scale [OOWS], Wang scale) questionnaires, and physiological parameters. For statistical analysis, the area under the curve between baseline and 20 minutes after drug administration of the outcome variables was calculated. RESULTS: Intravenous morphine-naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose-dependently (morphine-naloxone 100:1 > morphine-naloxone 200:1) increased SOWS-G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P < .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone. CONCLUSION: Morphine-naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine-naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse.

Case-based blended eLearning scenarios-adequate for competence development or more?

BACKGROUND: Learning, competence development and scientific thinking in medicine need several strategies to facilitate new diagnostic and therapeutic ways. The optimal collaboration between creative thinking and biomedical informatics provides innovation for the individual patient and for a medical school or society. Utilizing the flexibilities of an e­learning platform, a case based blended learning (CBBL) framework consisting of A) case based textbook material, B) online e­CBL with question driven learning scenarios and C) simulated patient (SP) contact seminars was developed and implemented in multiple medical fields. Real-life clinical cases were anonymized and transferred into an interactive and an interdisciplinary eLearning platform. METHODS: As an example of the offered clinical teaching-case collection, an example of a psychiatric case for the disease "posttraumatic stress disorder (PTSD)" is presented: a 30-year-old man with a history of insomnia with difficulties in falling asleep and sleeping through, nightmares, nervousness and psychomotor restlessness. The students are challenged to identify possible differential diagnoses and further get to know the patient's personal history (loss of relatives due to war, torture and flight from home country). Further, the students are guided through the principles of fear conditioning including translational aspects like neurotransmitter signaling of PTSD pathomechanism (translational and research aspects like dopamine transporter gene polymorphism, long term potentiation and synaptic signaling). RESULTS/CONCLUSION: The case presentation comprises different learning aspects: First, declarative knowledge has to be acquired and collected in basic medical sciences, knowledge that is in fact available and can be accessed on the conscious and preconscious level in long-term memory. Second, associative learning leads to the formation of neuronal connections and is an important way of learning and discovering, founded in neural associations. Third, polythematic-crosslinking thinking is needed as ability to link information in a meaningful way. These steps are a typical intellectual ability of gifted learners and researchers that combine previously seemingly unrelated areas to each other and drive innovation.

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.

ADMA and NT pro-BNP are associated with overall mortality in elderly.

BACKGROUND: Increased asymmetrical dimethylarginine (ADMA) and NT pro-BNP concentrations have been associated with mortality in patients with cardiovascular (CV) disease and the general population. The use of these prognostic markers in an older population is not established yet. The aim of the present study was to investigate the prognostic value of age, sex, BMI, co-medication and CV laboratory risk markers in geriatric care patients. MATERIALS AND METHODS: In this prospective observational single-centre cohort study data of long-term geriatric care patients were collected. Blood samples were collected between 14.09.2009 and 16.12.2009, and mortality was recorded up to 90 months. ADMA, its symmetric isomer SDMA, L-arginine, NT pro-BNP and CRP were determined at study entry. Simple associations of risk factors for survival period were explored by Spearman correlation coefficient. Significant univariate predictors for survival period were used in the Cox proportional hazard model. RESULTS: A total of 481 patients were screened, and data from 449 patients were analysed. A total of 381 patients died during the observation period. Full data sets from 344 patients were used for Cox regression analysis. Male sex, older age, lower BMI, use of neuroleptic medicine, peripheral artery disease, and elevated plasma concentrations of ADMA, NT pro-BNP, and CRP were significant predictors of mortality. CONCLUSION: The concentration of ADMA and NT pro-BNP may be used as an early risk marker for overall mortality in geriatric care. Neuroleptic medicine is associated with increased mortality in this population.

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.

Cardiovascular Effects of Stress During Acutely Increased Free Fatty Acids in a Randomized, Double-Blind, Cross-Over Study in Humans.

Increased free fatty acids stimulate sympathetic nervous system activity, impair endothelium-dependent vasodilation, and increase regional blood flow. The aim of this study was to assess if fatty acids acutely elevated by infusion of intralipid/heparin affect cardiovascular reactivity employing two stressors eliciting either a cardiac (Stroop test) or vascular (Cold Face test) dominated pressor response. Two stress tasks were performed in 20 healthy subjects (10 women, 10 men) before and during a 180-min intralipid/heparin or saline infusion as placebo on alternate trial days in a randomized crossover study design. Blood pressure, heart rate, cardiac index, and total peripheral resistance index were measured. At baseline, the Stroop test did not affect hemodynamic parameters, and the Cold Face test had an impact on hemodynamic parameters except for heart rate. Plasma fatty acids concentrations increased to 810% (t=11.0, p<0.001) of baseline and C-peptide increased by 17% (t=4.66, p<0.001) during intralipid/heparin infusion. This was paralleled by increased cardiac index (F=9.98; p<0.005 vs. saline) and reduced total peripheral resistance index (F=4.46; p<0.05 vs saline). There was no effect of intralipid/heparin or saline infusion on Stroop test or Cold Face test reactivity of hemodynamic parameters. An acute increase in free fatty acids does not affect the magnitude or pattern of stress response in healthy volunteers, but primarily alter the underlying cardiovascular tone by decreasing total peripheral resistance index and increasing cardiac index to maintain a constant blood pressure.

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.

Atorvastatin combined with ticagrelor prevent ischemia-reperfusion induced vascular endothelial dysfunction in healthy young males - A randomized, placebo-controlled, double-blinded study.

BACKGROUND: Atorvastatin and ticagrelor have been shown to prevent against tissue injury in animals. It is unclear if these beneficial effects are also detectable in humans. We studied the effect of high-dose atorvastatin combined with ticagrelor loading on endothelial dysfunction in a model of forearm vascular ischemia-reperfusion (IR) injury. METHODS: 32 healthy subjects (n=16 per group) were enrolled in this randomized, placebo-controlled, double-blinded trial. Forearm blood flow (FBF) measurements in response to increasing intra-arterial doses of the vasodilator acetylcholine (ACh; endothelium-dependent agonist) and glyceryltrinitrate (GTN; endothelium-independent) were performed before and after a cuff-induced 20min forearm ischemia, respectively. FBF reactivity was assessed prior to any pharmacological intervention and after 14days intake of 80mg atorvastatin once daily or placebo, followed by an oral loading dose of 180mg ticagrelor. In addition, lipoprotein parameters and platelet aggregation were evaluated. RESULTS: Ticagrelor loading mitigated ischemia-induced endothelial dysfunction and in combination with repeated atorvastatin dosing the response to ACh during reperfusion was completely normalized (FBF AChAUC ratio post- vs. pre-ischemia: 0.81 [ticagrelor] vs. 1.04 [atorvastatin+ticagrelor]; P=0.001). As expected, GTN-induced vasodilation was not affected by IR injury. Atorvastatin significantly reduced total and low density lipoprotein cholesterol concentrations, while high density lipoprotein cholesterol and triglyceride levels remained unchanged. CONCLUSION: Chronic atorvastatin treatment combined with ticagrelor loading prevents against endothelial dysfunction after acute forearm ischemia. Ticagrelor alone mitigated the impaired endothelium-dependent FBF response as compared to no pharmacological intervention. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02910778.

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.

Ticagrelor mitigates ischaemia-reperfusion induced vascular endothelial dysfunction in healthy young males - a randomized, single-blinded study.

AIMS: Animal data suggest that ticagrelor but not clopidogrel protects against tissue injury. It is unclear if this effect of ticagrelor is also detectable in humans. We studied the effect of ticagrelor and clopidogrel at standard clinical doses on endothelial dysfunction in an experimental model of forearm vascular ischaemia-reperfusion (IR) injury. METHODS: In a randomized, single-blinded trial, 24 subjects underwent forearm blood flow (FBF) measurements in response to the endothelium-dependent vasodilator acetylcholine (ACh) and to glyceryltrinitrate (GTN; endothelium-independent) before and after a 20 min forearm ischaemia. FBF reactivity was assessed after an oral loading dose of ticagrelor or clopidogrel and after 14 days of regular intake of maintenance doses of the study medicines. In addition, the effect on platelet inhibition was evaluated using multiple electrode aggregometry. RESULTS: ACh-induced vasodilation was impaired during reperfusion and not completely normalized by acute or chronic treatment with ticagrelor or clopidogrel (post- vs. pre-ischaemia). However, ticagrelor mitigated endothelial dysfunction compared to clopidogrel after loading (FBF AChAUC ratio post- vs. pre-ischaemia: 0.83 [0.70; 0.96] vs. 0.64 [0.56; 0.72]; P = 0.024) and after chronic administration (FBF AChAUC ratio: 0.86 [0.71; 1.00] vs. 0.66 [0.55; 0.77]; P = 0.027). As expected, GTN-induced vasodilation was not affected by ischaemia. Ticagrelor or clopidogrel treatment inhibited platelet activation to a similar degree. CONCLUSION: Our data indicate that ticagrelor treatment exerts a greater vascular salutary effect than clopidogrel during reperfusion after an acute vascular occlusion. IR-induced vascular injury cannot be prevented completely by administration of these antiplatelet agents at standard clinical doses.

Effect of long-term physical activity on PCSK9, high- and low-density lipoprotein cholesterol, and lipoprotein(a) levels: a prospective observational trial

INTRODUCTION    Since proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were introduced to the market, the interest in PCSK9 metabolism has increased dramatically. OBJECTIVES    We investigated prospectively the influence of long-term physical activity on PCSK9, highand low-density lipoprotein cholesterol (HDL-C and LDL-C, respectively), and lipoprotein(a) levels [Lp(a)]. PATIENTS AND METHODS    A total of 109 participants were recruited and instructed to increase their sport pensum by 75 min/wk of vigorous-intensity or 150 min/wk of moderate-intensity endurance training (or a mixture) within the calculated training pulse for 8 months. Stress tests were performed at baseline and at the end of the study to prove and quantify the performance gain. PCSK9 levels were measured at baseline and after 2, 6, and 8 months by an enzyme-linked immunosorbent assay. HDL-C, LDL-C, and Lp(a) levels were measured at baseline and every 2 months. RESULTS    The final study sample included 79 subjects, who showed a mean performance gain of 11.4%. Mean (SD) PCSK9 and HDL-C levels increased significantly from 224.7 (66.8) ng/ml to 243.4 (84.0) ng/ml (P = 0.04) and 58.3 (18.4) mg/dl to 61.1 (18.5) mg/dl (P = 0.014), respectively. Mean (SD) LDL-C levels decreased significantly from 115.0 (33.4) mg/dl to 109.8 (31.7) mg/dl (P = 0.04), but there was no significant change in mean (SD) Lp(a) levels: 37.9 (51.9) nmol/l to 43.3 (60.6) nmol/l; P = 0.218. CONCLUSIONS    Our study showed a decrease in LDL-C levels induced by a long-term physical activity with a simultaneous increase in PCSK9 levels. PCSK9 is essential in lipid metabolism and should not be basically considered as harmful. It is possible that a certain amount of PCSK9 is beneficial to ensure an adequate lipid supply.

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.