RESUMO
The physiological response to high-level endurance exercise, such as running a marathon, poses several beneficial but also potentially harmful metabolic changes. The objective of this study was to determine the impact of marathon (M) and ultra-marathon (UM) on inflammation and iron homeostasis in paired samples. Fifteen well-trained, non-professional endurance athletes (14 males, 1 female) performed both a 130 km ultra-marathon and a traditional 42.195 km marathon. We determined markers of inflammation and iron homeostasis before, immediately after, and within 5 days after finishing each run, respectively. Biomarkers of inflammation (leucocytes, neutrophil granulocytes, monocytes, and c-reactive protein [CRP]) increased significantly after both marathon and ultra-marathon with higher levels of CRP after ultra-marathon compared with marathon both immediately after the race (18.15 ± 12.41 vs 5.58 ± 9.65 mg/L, P < .001) and at follow-up (15.67 ± 16.97 vs 7.19 ± 7.75 mg/L, P = .045) Concentrations of ferritin also increased significantly after both races and remained high at follow-up. Higher levels of ferritin immediately after the race (111.5 ± 103.2 vs 84.8 ± 86.3, P = .001) and at follow-up (102.7 ± 79.5 vs 74.6 ± 65.6, P = .001) were found in ultra-marathon finishers. The observed increase of serum iron and transferrin saturation (TSAT) after marathon and the decrease of serum iron and TSAT after ultra-marathon resulted in a significant absolute difference between the two races. The present data suggest a higher degree of inflammation after ultra-marathon compared with marathon. Markers of iron homeostasis also showed different response patterns with regard to running distance.
Assuntos
Metabolismo Energético , Homeostase , Inflamação/sangue , Ferro/sangue , Corrida de Maratona/fisiologia , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Feminino , Ferritinas/sangue , Humanos , Leucócitos/metabolismo , Masculino , Monócitos/metabolismo , Músculo Esquelético/lesões , Músculo Esquelético/metabolismo , Neutrófilos/metabolismo , Estudos ProspectivosRESUMO
Extracellular vesicles (EV) act as a cellular communication tool by carrying lipids, proteins and micro RNA (miR) between cells, thereby playing a pivotal role in thromboembolic processes. The effect of P2Y12 inhibitors on pro-coagulatory, phosphatidylserine (PS)-expressing EV has been investigated previously, but only in vitro or during confounding clinical conditions, such as acute coronary syndrome. Hence, we enrolled 62 consecutive patients 12 month after percutaneous coronary intervention and stent implantation and consequent treatment with dual-antiplatelet therapy consisting of low-dose aspirin and P2Y12 inhibitors. Blood for platelet function testing and EV and miR measurements was taken on the last day of P2Y12 inhibitor intake (baseline, on-treatment) and 10, 30 and 180 days thereafter (off-treatment). We did not observe any influence of P2Y12 inhibitors on the levels of PS-EV or EV sub-population from platelets, erythrocytes, monocytes or endothelial cells, respectively. There was no relationship between platelet function and EV levels in plasma. However, the association of miR-21 and miR-150 with platelet EVs was significantly different between on- and off-treatment measurements. Hence, our study suggests no influence of P2Y12 inhibition on the count of EVs in plasma, but on the potential cargo of platelet-derived EV.
Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/genética , Vesículas Extracelulares/efeitos dos fármacos , Vesículas Extracelulares/metabolismo , MicroRNAs/sangue , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Idoso , Aspirina/farmacologia , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Fosfatidilserinas/sangue , Fosfatidilserinas/metabolismo , Cloridrato de Prasugrel/uso terapêutico , Ticagrelor/uso terapêuticoRESUMO
(1) Background: Extracellular vesicles (EVs) have been recognized as a cellular communication tool with cardioprotective properties; however, it is unknown whether cardioprotection by remote ischemic conditioning (RIC) involves EVs. (2) Methods: We randomized patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) to additionally receive a protocol of RIC or a sham-intervention. Blood was taken before and immediately, 24 h, four days and one month after PCI. Additionally, we investigated EVs from healthy volunteers undergoing RIC. EVs were characterized by a high-sensitive flow cytometer (Beckman Coulter Cytoflex S, Krefeld, Germany). (3) Results: We analyzed 32 patients (16 RIC, 16 control) and five healthy volunteers. We investigated platelet-, endothelial-, leukocyte-, monocyte- and granulocyte-derived EVs and their pro-thrombotic sub-populations expressing superficial phosphatidylserine (PS+). We did not observe a significant effect of RIC on the numbers of circulating EVs, although granulocyte-derived EVs were significantly higher in the RIC group. In line, RIC had not impact on EVs in healthy volunteers. Additionally, we observed changes of PS+/PEV, EEVs and PS+/CD15+ EVs irrespective of RIC with time following STEMI. 4) Conclusion: We provide further insights into the course of different circulating EVs during the acute and sub-acute phases of STEMI. With respect to the investigated EV populations, RIC seems to have no effect, with only minor differences found for granulocyte EVs.
RESUMO
OBJECTIVE: The emergency medical service (EMS) provides rapid pre-hospital diagnosis and transportation in ST-elevation myocardial infarction (STEMI) systems of care. Aim of the study was to assess temporal and regional characteristics of EMS-related delays in a metropolitan STEMI network. METHODS: Patient call-to-arrival of EMS at site (call-to-site), transportation time from site to hospital (site-to-door), call-to-door, patient's location, month, weekday, and hour of EMS activation were recorded in 4751 patients referred to a tertiary center with suspicion of STEMI. RESULTS: Median call-to-site, site-to-door, and call-to-door times were 9 (7-12), 39 (31-48), and 49 (41-59) minutes, respectively. The shortest transportation times were noted between 08:00 and 16:00 and in general on Sundays. They were significantly prolonged between midnight and 04:00, whereby the longest difference did not exceed 4 min in median. Patient's site of call had a major impact on transportation times, which were shorter in Central and Western districts as compared to Southern and Eastern districts of Vienna (p < 0.001 between-group difference for call-to-site, site-to-door, and call-to-door). After multivariable adjustment, patient's site of call was an independent predictor of call-to-site delay (p < 0.001). Moreover, age and hour of EMS activation were the strongest predictors of call-to-site, site-to-door, and call-to-door delays (p < 0.05). CONCLUSION: In our Viennese STEMI network, the strongest determinants of pre-hospital EMS-related transportation delays were patient's site of call, patient's age, and hour of EMS activation. Due to the significant but small median time delays, which are within the guideline-recommended time intervals, no impact on clinical outcome can be expected.
Assuntos
Serviços Médicos de Emergência/estatística & dados numéricos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Tempo para o Tratamento/estatística & dados numéricos , Transporte de Pacientes/estatística & dados numéricos , Fatores Etários , Idoso , Áustria , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
BACKGROUND: The efficacy of remote ischaemic conditioning in clinical trials of ST-segment elevation myocardial infarction (STEMI) or elective percutaneous coronary intervention is controversial. We aimed to systematically review and meta-analyse whether remote ischaemic conditioning reduces myocardial damage in those patients. METHODS: We searched PubMed, Embase and Web of Science from inception until December 2017 for randomised clinical trials evaluating remote ischaemic conditioning versus a control group. Two independent reviewers extracted data of 23 trials (2118 patients with STEMI; 2048 patients undergoing elective percutaneous coronary intervention) which were meta-analysed using random-effects models. RESULTS: Remote ischaemic conditioning reduced infarct size in STEMI patients when assessed by imaging (mean difference of infarct size as percentage of left ventricle -2.43, 95% confidence interval (CI) -4.37 to -0.48; P=0.01; I2=44%; n=925) or biomarkers related to myocardial injury (peak values of cardiac biomarker release reported as standardised mean difference -0.19, 95% CI -0.37 to -0.02; P=0.03; I2=58%; n=1483) and increased myocardial salvage index (mean difference 0.07, 95% CI 0.01 to 0.13; P=0.02; I2=49%; n= 636). Left ventricular ejection fraction was increased when assessed during the first days after STEMI (mean difference 1.53, 95% CI 0.23 to 2.83; P=0.02; I2=28%; n=1192). Remote ischaemic conditioning had no influence on biomarker values after elective percutaneous coronary intervention (standardised mean difference 0.06, 95% CI -0.17 to 0.30; P=0.59). CONCLUSIONS: Despite a statistically significant reduction of myocardial damage in STEMI patients, the magnitude of the reduction was small and a significant impact on clinical events is unlikely. With respect to elective percutaneous coronary intervention, remote ischaemic conditioning had no influence on myocardial injury and its use is not supported by our analysis.
Assuntos
Doença da Artéria Coronariana/cirurgia , Precondicionamento Isquêmico/métodos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Doença da Artéria Coronariana/fisiopatologia , Procedimentos Cirúrgicos Eletivos , Humanos , Imageamento por Ressonância Magnética , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Volume Sistólico , Tomografia Computadorizada de Emissão de Fóton Único , Troponina I/sangue , Troponina T/sangue , Função Ventricular EsquerdaRESUMO
BACKGROUND: An elevation of cardiac biomarkers is observed after intense or long-lasting physical activity. However, a recent meta-analysis has suggested that there might be an inverse relationship between duration of exercise and degree of biomarker elevation. The objective of this observational study was to investigate the impact of ultra-marathon (UM) vs. marathon (M) on biomarkers of myocyte necrosis and hemodynamic stress/congestion. METHODS: Well-trained endurance athletes were recruited to participate in a 130-km UM and a M run. Troponin I (TnI), creatine kinase (CK), N-terminal pro-brain natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), and copeptin were measured after both events, respectively. RESULTS: Fifteen athletes (14 males, one female) were included. There was no difference in exercise intensity according to the Borg scale (UM 16 [IQR 15-17], M 16 [IQR 14-17]; p = 0.424). Biomarkers of myocyte necrosis both differed significantly with higher levels of TnI (UM 0.056 ng/L [IQR 0.022-0.104), M 0.028 ng/L [IQR 0.022-0.049]; p = 0.016) and CK (UM 6992 U/l [IQR 2886-23038], M 425 U/l [IQR 327-681]; p = 0.001) after UM compared to M. Also, NT-proBNP (UM 723 ng/L [IQR 378-1152], M 132 ng/L [IQR 64-198]; p = 0.001) and MR-proADM (UM 1.012 nmol/L [IQR 0.753-0.975], M 0.877 nmol/L [IQR 0.550-0.985]; p = 0.023) as markers of myocardial congestion were significantly higher after UM. There was a tendency for elevated copeptin levels after M, but did not reach statistical significance (p = 0.078). CONCLUSION: Ultra-marathon is associated with higher levels of biomarkers of myocyte necrosis and cardiac congestion compared to marathon, highlighting the impact of exercise duration on the cardiovascular system.
Assuntos
Atletas , Corrida de Maratona/fisiologia , Miócitos Cardíacos/metabolismo , Peptídeo Natriurético Encefálico/sangue , Necrose/sangue , Fragmentos de Peptídeos/sangue , Troponina I/sangue , Troponina T/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/patologia , Necrose/patologia , Estudos Prospectivos , Precursores de Proteínas , Adulto JovemRESUMO
BACKGROUND: Patients with familial hypercholesterolemia (FH) are at increased risk for premature and subsequent cardiovascular disease. Data on long-term major adverse cardiovascular events (MACE) in patients with FH after percutaneous coronary intervention (PCI) in the era of high-intensity statins are scarce. OBJECTIVE: We assessed the prognostic impact of clinically diagnosed FH on long-term MACE, a composite of all-cause death, myocardial infarction, and ischemic stroke in patients admitted for stable coronary artery disease (SCAD) or acute coronary syndromes (ACSs) undergoing PCI. METHODS: FH was diagnosed according to the Dutch Lipid Clinic Network diagnosis criteria: "Unlikely FH" diagnosis was defined as 0 to 2 points, "possible FH" as 3 to 5 points, and "probable/definite FH" diagnosis as 6 or higher. RESULTS: From a total of 1550 eligible patients (47.4% were admitted for SCAD and 52.6% for ACS), 77 (5.0%) were classified as probable/definite FH, 332 (21.4%) as possible FH, and 1141 (73.6%) as unlikely FH. Mean follow-up was 6.0 ± 2.4 years. After adjustment for possible confounders, patients classified with probable or definite FH (hazard ratio [HR] 1.922 [95% confidence interval (CI) 1.220-2.999]; P = .004), but not patients with possible FH (HR 1.105 [95% CI 0.843-1.447]; P = .470) faced a significant, approximately 2-fold increased risk of MACE compared with patients with unlikely FH. CONCLUSION: After adjustment for confounders, patients with probable or definite FH faced an approximate 2-fold increased risk for long-term MACE compared with patients without FH despite the widespread use of high-intensity statins. The new option of proprotein convertase subtilisin/kexin type 9 gene inhibitors in addition to other current optimal lipid-lowering strategies might help to further improve clinical outcome in patients with probable/definite FH.
Assuntos
Doenças Cardiovasculares/diagnóstico , Hiperlipoproteinemia Tipo II/diagnóstico , Intervenção Coronária Percutânea/métodos , Idoso , Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/mortalidade , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/mortalidade , Hiperlipoproteinemia Tipo II/terapia , Masculino , Pessoa de Meia-Idade , Inibidores de PCSK9 , Complicações Pós-Operatórias , Prevalência , Prognóstico , Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Data obtained from registries have shown that women diagnosed with STEMI are older, have more co-morbidities and a worse clinical outcome than men. Aim of this study was to investigate potential gender differences in in-hospital and long-term mortality in patients from Vienna STEMI registry (2003-2009). PATIENTS AND METHODS: Data from 4593 patients who were enrolled from January 2003 until December 2009 into the Vienna STEMI registry were analyzed. Gender-related differences in patient characteristics, time delays, reperfusion therapy, as well as short- and long-term all-cause mortality were investigated. A landmark analysis was performed to assess long-term all-cause mortality in patients after discharge. Multivariate regression analysis was performed in order to correct for confounders. RESULTS: Mean age, history of hypertension, diabetes mellitus and shock at presentation were significantly higher in women compared to men, whereas men were more frequently smokers, had more frequently a positive family history, a history of previous myocardial infarction and received more often GbIIb/IIIa inhibitors and reperfusion therapy. Overall the only significant difference in time delays was found in the onset of pain-to first medical contact time, which was significantly prolonged in women. Unadjusted in-hospital mortality, long-term mortality and long-term mortality for in-hospital survivors were statistically higher for women. After adjustment for confounders, multivariate analysis revealed no differences in mortalities between males and females. CONCLUSION: The higher risk profile and the prolonged delay between onset of pain-to-first medical contact are responsible for the higher unadjusted mortality rates in women. Difference in short and long-term mortalities is no more existent after statistical correction for confounders such as age, co-morbidities and significantly different time delay.