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1.
Biomolecules ; 10(8)2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32796765

RESUMO

Recently, the stabilization of the endothelium has been explicitly identified as a therapeutic goal in coronavirus disease 2019 (COVID-19). Adrecizumab (HAM8101) is a first-in-class humanized monoclonal anti-Adrenomedullin (anti-ADM) antibody, targeting the sepsis- and inflammation-based vascular and capillary leakage. Within a "treatment on a named-patient basis" approach, Adrecizumab was administered to eight extreme-critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). The patients received a single dose of Adrecizumab, which was administered between 1 and 3 days after the initiation of mechanical ventilation. The SOFA (median 12.5) and SAPS-II (median 39) scores clearly documented the population at highest risk. Moreover, six of the patients suffered from acute renal failure, of whom five needed renal replacement therapy. The length of follow-up ranged between 13 and 27 days. Following the Adrecizumab administration, one patient in the low-dose group died at day 4 due to fulminant pulmonary embolism, while four were in stable condition, and three were discharged from the intensive care unit (ICU). Within 12 days, the SOFA score, as well as the disease severity score (range 0-16, mirroring critical resources in the ICU, with higher scores indicating more severe illness), decreased in five out of the seven surviving patients (in all high-dose patients). The PaO2/FiO2 increased within 12 days, while the inflammatory parameters C-reactive protein, procalcitonin, and interleukin-6 decreased. Importantly, the mortality was lower than expected and calculated by the SOFA score. In conclusion, in this preliminary uncontrolled case series of eight shock patients with life-threatening COVID-19 and ARDS, the administration of Adrecizumab was followed by a favorable outcome. Although the non-controlled design and the small sample size preclude any definitive statement about the potential efficacy of Adrecizumab in critically ill COVID-19 patients, the results of this case series are encouraging.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Infecções por Coronavirus/complicações , Endotélio Vascular/efeitos dos fármacos , Pneumonia Viral/complicações , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Sepse/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Infecções por Coronavirus/patologia , Estado Terminal , Endotélio Vascular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Síndrome do Desconforto Respiratório do Adulto/etiologia , Sepse/etiologia
2.
Eur Heart J Acute Cardiovasc Care ; : 2048872620924198, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32700543

RESUMO

BACKGROUND: Most studies assessing the diagnostic value of high-sensitivity troponin in the diagnosis of myocardial infarction used batch-wise analyses of frozen samples for high-sensitivity troponin measurements. Whether the accuracy of these batch-wise high-sensitivity troponin measurements described in diagnostic studies is comparable to clinical routine is unknown. METHODS: We enrolled 937 patients presenting with suspected myocardial infarction in this prospective cohort study. Measurements of high-sensitivity troponin I (Abbott Architect) and high-sensitivity troponin T (Roche) were performed in two settings: (a) on-demand in clinical routine using fresh blood samples; and (b) in batches using frozen blood samples from the same individuals at three timepoints (0 hours, 1 hour and 3 hours after presentation). RESULTS: Median troponin levels were not different between on-demand and batch-wise measurements. Troponin levels in the range of 0 to 40 ng/L showed a very high correlation between the on-demand and batch setting (Pearson correlation coefficient (r) was 0.92-0.95 for high-sensitivity troponin I and 0.96 for high-sensitivity troponin T). However, at very low troponin levels (0 to 10 ng/L) correlation between the two settings was moderate (r for high-sensitivity troponin I 0.59-0.66 and 0.65-0.69 for high-sensitivity troponin T). Application of guideline-recommended rapid diagnostic algorithms showed similar diagnostic performance with both methods. CONCLUSIONS: Overall on-demand and batch-wise measurements of high-sensitivity troponin provided similar results, but their correlation was moderate, when focusing on very low troponin levels. The application of rapid diagnostic algorithms was safe in both settings.Trial Registration: www.clinicaltrials.gov (NCT02355457).

3.
Eur Heart J ; 41(34): 3255-3268, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32484517

RESUMO

AIMS: Takotsubo syndrome (TTS) is an acute heart failure syndrome, which shares many features with acute coronary syndrome (ACS). Although TTS was initially described with angiographically normal coronary arteries, smaller studies recently indicated a potential coexistence of coronary artery disease (CAD) in TTS patients. This study aimed to determine the coexistence, features, and prognostic role of CAD in a large cohort of patients with TTS. METHODS AND RESULTS: Coronary anatomy and CAD were studied in patients diagnosed with TTS. Inclusion criteria were compliance with the International Takotsubo Diagnostic Criteria for TTS, and availability of original coronary angiographies with ventriculography performed during the acute phase. Exclusion criteria were missing views, poor quality of angiography loops, and angiography without ventriculography. A total of 1016 TTS patients were studied. Of those, 23.0% had obstructive CAD, 41.2% had non-obstructive CAD, and 35.7% had angiographically normal coronary arteries. A total of 47 patients (4.6%) underwent percutaneous coronary intervention, and 3 patients had acute and 8 had chronic coronary artery occlusion concomitant with TTS, respectively. The presence of CAD was associated with increased incidence of shock, ventilation, and death from any cause. After adjusting for confounders, the presence of obstructive CAD was associated with mortality at 30 days. Takotsubo syndrome patients with obstructive CAD were at comparable risk for shock and death and nearly at twice the risk for ventilation compared to an age- and sex-matched ACS cohort. CONCLUSIONS: Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01947621.

4.
J Am Coll Cardiol ; 75(16): 1869-1877, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32327096

RESUMO

BACKGROUND: Takotsubo syndrome (TTS) occurs predominantly in post-menopausal women but is also found in younger patients. OBJECTIVES: This study aimed to investigate age-related differences in TTS. METHODS: Patients diagnosed with TTS and enrolled in the International Takotsubo Registry between January 2011 and February 2017 were included in this analysis and were stratified by age (younger: ≤50 years, middle-age: 51 to 74 years, elderly: ≥75 years). Baseline characteristics, hospital course, as well as short- and long-term mortality were compared among groups. RESULTS: Of 2,098 TTS patients, 242 (11.5%) patients were ≤50 years of age, 1,194 (56.9%) were 51 to 74 years of age, and 662 (31.6%) were ≥75 years of age. Younger patients were more often men (12.4% vs. 10.9% vs. 6.3%; p = 0.002) and had an increased prevalence of acute neurological (16.3% vs. 8.4% vs. 8.8%; p = 0.001) or psychiatric disorders (14.1% vs. 10.3% vs. 5.6%; p < 0.001) compared with middle-aged and elderly TTS patients. Furthermore, younger patients had more often cardiogenic shock (15.3% vs. 9.1% vs. 8.1%; p = 0.004) and had a numerically higher in-hospital mortality (6.6% vs. 3.6% vs. 5.1%; p = 0.07). At multivariable analysis, younger (odds ratio: 1.60; 95% confidence interval: 0.86 to 3.01; p = 0.14) and older age (odds ratio: 1.09; 95% confidence interval: 0.66 to 1.80; p = 0.75) were not independently associated with in-hospital mortality using the middle-aged group as a reference. There were no differences in 60-day mortality rates among groups. CONCLUSIONS: A substantial proportion of TTS patients are younger than 50 years of age. TTS is associated with severe complications requiring intensive care, particularly in younger patients.

5.
J Am Heart Assoc ; 9(8): e015452, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32299288

RESUMO

Background Risk stratification among patients with coronary artery disease (CAD) is of considerable interest due to the potential to guide secondary preventive therapies. Thus, we evaluated the predictive value of soluble urokinase-type plasminogen activator receptor (suPAR) levels for cardiovascular mortality and nonfatal myocardial infarction in patients with CAD. Methods and Results Plasma levels of suPAR were measured in a cohort of 1703 patients with documented CAD as evidenced by coronary angiography-including 626 patients with acute coronary syndrome and 1077 patients with stable angina pectoris. Cardiovascular death and/or nonfatal myocardial infarction were defined as main outcome measures. During a median follow-up of 3.5 years, suPAR levels reliably predicted cardiovascular death or myocardial infarction in CAD, evidenced by survival curves stratified for tertiles of suPAR levels. In Cox regression analyses, the hazard ratio for the prediction of cardiovascular death and/or myocardial infarction was 2.19 (P<0.001) in the overall cohort and 2.56 in the acute coronary syndrome cohort (P<0.001). Even after adjustment for common cardiovascular risk factors, renal function and the biomarkers C-reactive protein, N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I suPAR still enabled a reliable prediction of cardiovascular death or myocardial infarction with a hazard ratio of 1.61 (P=0.022) in the overall cohort and 2.22 (P=0.005) in the acute coronary syndrome cohort. Conclusions SuPAR has a strong and independent prognostic value in secondary prevention settings, and thereby might represent a valuable biomarker for risk estimation in CAD.

6.
J Am Heart Assoc ; 9(9): e015480, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32321351

RESUMO

Background Coronary heart disease is a leading cause of mortality worldwide. Iron deficiency, a frequent comorbidity of coronary heart disease, causes an increased expression of transferrin receptor and soluble transferrin receptor levels (sTfR) levels, while iron repletion returns sTfR levels to the normal physiological range. Recently, sTfR levels were proposed as a potential new marker of iron metabolism in cardiovascular diseases. Therefore, we aimed to evaluate the prognostic value of circulating sTfR levels in a large cohort of patients with coronary heart disease. Methods and Results The disease cohort comprised 3423 subjects who had angiographically documented coronary heart disease and who participated in the AtheroGene study. Serum levels of sTfR were determined at baseline using an automated immunoassay (Roche Cobas Integra 400). Two main outcomes were considered: a combined end point of myocardial infarction and cardiovascular death and cardiovascular death alone. During a median follow-up of 4.0 years, 10.3% of the patients experienced an end point. In Cox regression analyses for sTfR levels, the hazard ratio (HR) for future cardiovascular death and/or myocardial infarction was 1.27 (95% CI, 1.11-1.44, P<0.001) after adjustment for sex and age. This association remained significant (HR, 1.23; 95% CI, 1.03-1.46, P=0.02) after additional adjustment for body mass index, smoking status, hypertension, diabetes mellitus, dyslipidemia, C-reactive protein, and surrogates of cardiac function, size of myocardial necrosis (hs-Tnl), and hemoglobin levels. Conclusions In this large cohort study, sTfR levels were strongly associated with future myocardial infarction and cardiovascular death. This implicates a role for sTfR in secondary cardiovascular risk prediction.

7.
Clin Res Cardiol ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32215702

RESUMO

BACKGROUND: Iron deficiency is now accepted as an independent entity beyond anemia. Recently, a new functional definition of iron deficiency was proposed and proved strong efficacy in randomized cardiovascular clinical trials of intravenous iron supplementation. Here, we characterize the impact of iron deficiency on all-cause mortality in the non-anemic general population based on two distinct definitions. METHODS: The Gutenberg Health Study is a population-based, prospective, single-center cohort study. The 5000 individuals between 35 and 74 years underwent baseline and a planned follow-up visit at year 5. Tested definitions of iron deficiency were (1) functional iron deficiency-ferritin levels below 100 µg/l, or ferritin levels between 100 and 299 µg/l and transferrin saturation below 20%, and (2) absolute iron deficiency-ferritin below 30 µg/l. RESULTS: At baseline, a total of 54.5% of participants showed functional iron deficiency at a mean hemoglobin of 14.3 g/dl; while, the rate of absolute iron deficiency was 11.8%, at a mean hemoglobin level of 13.4 g/dl. At year 5, proportion of newly diagnosed subjects was 18.5% and 4.8%, respectively. Rate of all-cause mortality was 7.2% (n = 361); while, median follow-up was 10.1 years. After adjustment for hemoglobin and major cardiovascular risk factors, the hazard ratio with 95% confidence interval of the association of iron deficiency with mortality was 1.3 (1.0-1.6; p = 0.023) for the functional definition, and 1.9 (1.3-2.8; p = 0.002) for absolute iron deficiency. CONCLUSIONS: Iron deficiency is very common in the apparently healthy general population and independently associated with all-cause mortality in the mid to long term.

8.
Biomolecules ; 10(3)2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143410

RESUMO

Risk stratification among patients with coronary artery disease (CAD) is of considerable interest to potentially guide secondary preventive therapies. Cardiac troponins as well as C-reactive protein (hsCRP) and natriuretic peptides have emerged as biomarkers for risk stratification. The question remains if one of these biomarkers is superior in predicting adverse outcomes. Thus, we perform a head-to-head comparison between high-sensitivity troponin I (hsTnI), hsCRP, and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with CAD. Plasma levels were measured in a cohort of 2193 patients with documented CAD. The main outcome measures were cardiovascular (CV) death and/or nonfatal myocardial infarction (MI). During a median follow-up of 3.8 years, all three biomarkers were associated with cardiovascular death and/or MI. After adjustments for conventional cardiovascular risk factors, the hazard ratio (HR) per standard deviation (SD) for the prediction of CV death and/or nonfatal MI was 1.39 [95% CI: 1.24-1.57, p < 0.001] for hsTnI, 1.41 [95% CI: 1.24-1.60, p < 0.001] for hsCRP, and 1.64 [95% CI: 1.39-1.92, p < 0.001] for NT-proBNP. However, upon further adjustments for the other two biomarkers, only NT-proBNP was still associated with the combined endpoint with an HR of 1.47 [95% CI: 1.19-1.82, p < 0.001]. Conclusively, NT-proBNP is reliably linked to CV death and MI in patients with CAD and provides incremental value beyond hsCRP and hsTnI.

9.
Biomolecules ; 10(1)2020 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-31940748

RESUMO

Cardiovascular diseases (CVDs) comprise 45% of all deaths in Europe and causes 3.9 million deaths annually. Coronary artery disease (CAD) which includes myocardial infarction (MI) represents the most common form of CVD. A relevant proportion of MI cases seems preventable since reports claim that up to two-thirds of these patients exhibit symptoms suggestive for MI within 12 months prior to the acute MI event. An early identification of these at-risk subjects is necessary to manage an early and efficient treatment during the ischemic phase. The aim of the PRecision MEDicine in Coronary Artery Disease (PREMED-CAD) consortium is to apply a system medicine approach towards studying and identifying an ischemia specific 'biomarker signature' that improves the identification of individuals 'at-risk' for acute MI. The consortium will take an interdisciplinary and translational approach integrating knowledge from CAD epidemiology, imaging, bioinformatics, statistics and molecular biology, as well as existing phenotypic, blood-based and clinical biomarker data of distinct CAD and subclinical MI phenotypes. This biomarker signature will be validated through atherosclerosis-prone mouse models and human cohorts. The validated signature will be translated in a real-world clinical setting using an ongoing clinical trial comprising patients with subclinical ischemia. The aim of the knowledge obtained from this project is to aid in early MI detection and reduce the mortality and morbidity rate in these at-risk MI individuals.

10.
Arterioscler Thromb Vasc Biol ; 40(1): 279-287, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31766870

RESUMO

OBJECTIVE: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×103 cells/µL emerged as independent predictors for thrombus formation or embolism. CONCLUSIONS: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.


Assuntos
Embolia/etiologia , Sistema de Registros , Medição de Risco/métodos , Cardiomiopatia de Takotsubo/complicações , Trombose/etiologia , Idoso , Austrália/epidemiologia , Angiografia Coronária , Eletrocardiografia , Embolia/diagnóstico , Embolia/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Cardiopatias/etiologia , Ventrículos do Coração , Humanos , Incidência , Imagem Cinética por Ressonância Magnética , Masculino , Ventriculografia com Radionuclídeos , Fatores de Risco , Taxa de Sobrevida/tendências , Cardiomiopatia de Takotsubo/diagnóstico , Trombose/diagnóstico , Trombose/epidemiologia , Fatores de Tempo , Estados Unidos/epidemiologia
11.
Eur J Heart Fail ; 22(2): 330-337, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31863563

RESUMO

AIMS: The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS). METHODS AND RESULTS: Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50-3.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78-1.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting. CONCLUSION: In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621.

12.
Eur J Prev Cardiol ; : 2047487319885458, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31707846

RESUMO

BACKGROUND: Modifiable lifestyle risk factors (modRF) of coronary artery disease (CAD) are associated with increased inflammation represented by elevated C-reactive protein (CRP) levels. Lifestyle changes may influence the inflammatory burden in patients with CAD, relevantly modifying the target population for emerging anti-inflammatory compounds. AIMS: The aims of this study were to analyse the association of modRF and CRP levels in CAD patients, and to define a potential target population for anti-inflammatory treatment with and without the optimisation of modRF. METHODS: We included all patients with angiographically documented CAD from the observational cohort study INTERCATH. Patients with recent myocardial infarction, malignancy, infectious disease, and pre-existing immunosuppressive medication including a history of solid organ transplantation were excluded. Overweight (body mass index (BMI) ≥ 25 kg/m2), smoking, lack of physical activity (PA; <1.5 h/week), and poor diet (≤12 points of an established Mediterranean diet score (MDS), range 0-28 points) were considered as modRF. CRP was measured by a high-sensitivity assay (hsCRP) at baseline. We performed multivariable linear regressions with log-transformed hsCRP as the dependent variable. Based on these associations, we calculated potential hsCRP levels for each patient, assuming optimisation of the individual modRF. RESULTS: Of 1014 patients, 737 (73%) were male, the mean age was 69 years, and 483 (48%) had an hsCRP ≥ 2 mg/l. ModRF were significantly overrepresented in patients with hsCRP ≥ 2 mg/l compared to patients with an hsCRP < 2 mg/l (BMI ≥ 25 kg/m2: 76% vs 61%; PA < 1.5 h/week: 69% vs 57%; MDS ≤ 12: 46% vs 37%; smoking: 61% vs 54%; p < 0.05 for all). hsCRP increased with the incremental number of modRF present (median hsCRP values for N = 0, 1, 2, 3, and 4 modRF: 1.1, 1.0, 1.6, 2.4, 2.8 mg/l, p < 0.001). Multivariable linear regression adjusting for age, sex, intake of lipid-lowering medication, and diabetes mellitus revealed independent associations between log-transformed hsCRP and all modRF (BMI ≥ 25 kg/m2: exp(ß) = 1.55, p < 0.001; PA < 1.5 h/week: exp(ß) = 1.33, p < 0.001; MDS ≤ 12: exp(ß) = 1.18, p = 0.018; smoking: exp(ß) = 1.18, p = 0.019). Individual recalculation of hsCRP levels assuming optimisation of modRF identified 183 out of 483 (38%) patients with hsCRP ≥ 2 mg/l who could achieve an hsCRP < 2 mg/l via lifestyle changes. CONCLUSION: modRF are strongly and independently associated with CRP levels in patients with CAD. A relevant portion of CAD patients with high inflammatory burden could achieve an hsCRP < 2 mg/l by lifestyle changes alone. This should be considered both in view of the cost and side-effects of pharmacological anti-inflammatory treatment and for the design of future clinical trials in this field.

13.
J Am Heart Assoc ; 8(21): e011194, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31672100

RESUMO

Background Left ventricular (LV) recovery in takotsubo syndrome (TTS) occurs over a wide-ranging interval, varying from hours to weeks. We sought to investigate the clinical predictors and prognostic impact of recovery time for TTS patients. Methods and Results TTS patients from the International Takotsubo Registry were included in this study. Cut-off for early LV recovery was determined to be 10 days after the acute event. Multivariable logistic regression was used to assess factors associated with the absence of early recovery. In-hospital outcomes and 1-year mortality were compared for patients with versus without early recovery. We analyzed 406 patients with comprehensive and serial imaging data regarding time to recovery. Of these, 191 (47.0%) had early LV recovery and 215 (53.0%) demonstrated late LV improvement. Patients without early recovery were more often male (12.6% versus 5.2%; P=0.011) and presented more frequently with typical TTS (76.3% versus 67.0%, P=0.040). Cardiac and inflammatory markers were higher in patients without early recovery than in those with early recovery. Patients without early recovery showed unfavorable 1-year outcome compared with patients with early recovery (P=0.003). On multiple logistic regression, male sex, LV ejection fraction <45%, and acute neurologic disorders were associated with the absence of early recovery. Conclusions TTS patients without early LV recovery have different clinical characteristics and less favorable 1-year outcome compared with patients with early recovery. The factors associated with the absence of early recovery included male sex, reduced LV ejection fraction, and acute neurologic events. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

14.
JAMA Cardiol ; 4(12): 1270-1279, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31664431

RESUMO

Importance: Risk stratification for coronary heart disease (CHD) remains challenging because of the complex causative mechanism of the disease. Metabolomic profiling offers the potential to detect new biomarkers and improve CHD risk assessment. Objective: To evaluate the association between circulating metabolites and incident CHD in a large European cohort. Design, Setting, and Participants: This population-based study used the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) case-cohort to measure circulating metabolites using a targeted approach in serum samples from 10 741 individuals without prevalent CHD. The cohort consisted of a weighted, random subcohort of the original cohort of more than 70 000 individuals. The case-cohort design was applied to 6 European cohorts: FINRISK97 (Finland), Monitoring of Trends and Determinants in Cardiovascular Diseases/Cooperative Health Research in the Region of Augsburg (MONICA/KORA; Germany), MONICA-Brianza and Moli-sani (Italy), DanMONICA (Denmark), and the Scottish Heart Health Extended Cohort (United Kingdom). Main Outcomes and Measures: Associations with time to CHD onset were assessed individually by applying weighted and adjusted Cox proportional hazard models. The association of metabolites with CHD onset was examined by C indices. Results: In 10 741 individuals (4157 women [38.7%]; median [interquartile range] age, 56.5 [49.2-62.2] years), 2166 incident CHD events (20.2%) occurred over a median (interquartile range) follow-up time of 9.2 (4.5-15.0) years. Among the 141 metabolites analyzed, 24 were significantly associated with incident CHD at a nominal P value of .05, including phosphatidylcholines (PCs), lysoPCs, amino acids, and sphingolipids. Five PCs remained significant after correction for multiple testing: acyl-alkyl-PC C40:6 (hazard ratio [HR], 1.13 [95% CI, 1.07-1.18]), diacyl-PC C40:6 (HR, 1.10 [95% CI, 1.04-1.15]), acyl-alkyl-PC C38:6 (HR, 1.11 [95% CI, 1.05-1.16]), diacyl-PC C38:6 (HR, 1.09 [95% CI, 1.04-1.14]) and diacyl-PC C38:5 (HR, 1.10 [95% CI, 1.05-1.16]). Lower levels of these metabolites were associated with increased risk of incident CHD. The strength of the associations competes with those of classic risk factors (C statistics: acyl-alkyl-PC C40:6, 0.756 [95% CI, 0.738-0.774], diacyl-PC C40:6, 0.754 [95% CI, 0.736-0.772], acyl-alkyl-PC C38:6, 0.755 [95% CI, 0.736-0.773], diacyl-PC C38:6, 0.754 [95% CI, 0.736-0.772]), diacyl-PC C38:5, 0.754 [95% CI, 0.736-0.772]). Adding metabolites to a base risk model including classic risk factors high-sensitivity C-reactive protein and high-sensitivity troponin I did not improve discrimination by C statistics. Conclusions and Relevance: Five PCs were significantly associated with increased risk of incident CHD and showed comparable discrimination with individual classic risk factors. Although these metabolites do not improve CHD risk assessment beyond that of classic risk factors, these findings hold promise for an improved understanding of the pathophysiology of CHD.

16.
J Am Heart Assoc ; 8(15): e010881, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31311438

RESUMO

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short- and long-term mortality. A subanalysis was performed comparing long-term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long-term mortality was higher in patients with malignancy (P<0.001), while short-term outcome was comparable (P=0.17). In a subanalysis, long-term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long-term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.

17.
Biomolecules ; 9(5)2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31108918

RESUMO

(1) Background: Telomeres are repetitive DNA sequences located at the extremities of chromosomes that maintain genetic stability. Telomere biology is relevant to several human disorders and diseases, specifically cardiovascular disease. To better understand the link between cardiovascular disease and telomere length, we studied the effect of relative telomere length (RTL) on cardiovascular risk factors in a large population-based sample. (2) Methods: RTL was measured by a real-time quantitative polymerase chain reaction in subjects of the population-based Gutenberg Health Study (n = 4944). We then performed an association study of RTL with known cardiovascular risk factors of smoking status as well as systolic and diastolic blood pressure, body mass index (BMI), LDL cholesterol, HDL cholesterol, and triglycerides. (3) Results: A significant correlation was shown for RTL, with age as a quality control in our study (effect = -0.004, p = 3.2 × 10-47). Analysis of the relation between RTL and cardiovascular risk factors showed a significant association of RTL in patients who were current smokers (effect = -0.016, p = 0.048). No significant associations with RTL were seen for cardiovascular risk factors of LDL cholesterol (p = 0.127), HDL cholesterol (p = 0.713), triglycerides (p = 0.359), smoking (p = 0.328), diastolic blood pressure (p = 0.615), systolic blood pressure (p = 0.949), or BMI (p = 0.903). In a subsequent analysis, we calculated the tertiles of RTL. No significant difference across RTL tertiles was detectable for BMI, blood pressure, lipid levels, or smoking status. Finally, we studied the association of RTL and cardiovascular risk factors stratified by tertiles of age. We found a significant association of RTL and LDL cholesterol in the oldest tertile of age (effect = 0.0004, p = 0.006). (4) Conclusions: We determined the association of relative telomere length and cardiovascular risk factors in a population setting. An association of telomere length with age, current smoking status, as well as with LDL cholesterol in the oldest tertile of age was found, whereas no associations were observed between telomere length and triglycerides, HDL cholesterol, blood pressure, or BMI.


Assuntos
Doenças Cardiovasculares/genética , Homeostase do Telômero , Fatores Etários , Idoso , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/epidemiologia , Triglicerídeos/sangue
18.
Eur Heart J ; 40(26): 2142-2151, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31098611

RESUMO

AIMS: We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS). METHODS AND RESULTS: We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P < 0.001) and 5-year mortality (68.9% vs. 16.7%, P < 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission. CONCLUSIONS: Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.

19.
Clin Res Cardiol ; 108(12): 1386-1393, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30989318

RESUMO

BACKGROUND: Early risk stratification of patients with suspected acute myocardial infarction (AMI) constitutes an unmet need in current daily clinical practice. We aimed to evaluate the predictive value of soluble urokinase-type plasminogen activator receptor (suPAR) levels for 1-year mortality in patients with suspected AMI. METHODS AND RESULTS: suPAR levels were determined in 1314 patients presenting to the emergency department with suspected AMI. Patients were followed up for 12 months to assess all-cause mortality. Of 1314 patients included, 308 were diagnosed with AMI. Median suPAR levels did not differ between subjects with AMI compared to non-AMI (3.5 ng/ml vs. 3.2 ng/ml, p = 0.066). suPAR levels reliably predicted all-cause mortality after 1 year. Hazard ratio for 1-year mortality was 12.6 (p < 0.001) in the quartile with the highest suPAR levels compared to the first quartile. The prognostic value for 6-month mortality was comparable to an established risk prediction model, the Global Registry of Acute Coronary Events (GRACE) score, with an AUC of 0.79 (95% CI 0.72-0.86) for the GRACE score and 0.77 (95% CI 0.69-0.84) for suPAR. Addition of suPAR improved the GRACE score, as shown by integrated discrimination improvement statistics of 0.036 (p = 0.03) suggesting a further discrimination of events from non-events by the addition of suPAR. CONCLUSIONS: suPAR levels reliably predicted mortality in patients with suspected AMI. STUDY REGISTRATION: http://www.clinicaltrials.gov (NCT02355457).


Assuntos
Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo
20.
Biomolecules ; 9(3)2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30889909

RESUMO

The soluble urokinase-type plasminogen activator receptor (suPAR) is a new marker for immune activation and inflammation and may provide diagnostic value on top of established biomarkers in patients with suspected acute myocardial infarction (AMI). Here, we evaluate the diagnostic potential of suPAR levels on top of high-sensitivity troponin I (hs-TnI) in a cohort of patients with suspected AMI. A total of 1220 patients presenting to the emergency department with suspected AMI were included, of whom 245 were diagnosed with AMI. Median suPAR levels at admission were elevated in subjects with AMI compared to non-AMI (3.8 ng/mL vs 3.3 ng/mL, p = 0.001). In C-statistics, the area under the curve (AUC) regarding the diagnosis of AMI was low (0.57 at an optimized cut-off of 3.7 ng/mL). Moreover, baseline suPAR levels on top of troponin values at admission and hour 1 reduced the number of patients who were correctly ruled-out as non-AMI, and who were correctly ruled-in as AMI. Our study shows that circulating levels of suPAR on top of high-sensitivity troponin I do not improve the early diagnosis of AMI.


Assuntos
Infarto do Miocárdio/diagnóstico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/análise , Troponina I/análise , Doença Aguda , Idoso , Biomarcadores/análise , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Solubilidade
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