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1.
Clin Res Cardiol ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034482

RESUMO

BACKGROUND: We aimed to investigate changes of incidence, outcome and related interventions of patients with acute coronary syndrome (ACS) over the past decade in Germany. METHODS: Data on the international statistical classification of diseases and procedural codes from the Federal Bureau of Statistics in Germany was used. This included all ACS cases in Germany in the years 2005-2015. Analyses were performed separately for the diagnoses of overall ACS, ST-elevation myocardial infarction (MI), non-ST-elevation MI and unstable angina pectoris. Procedures including coronary angiography and percutaneous coronary intervention and the endpoint in-hospital mortality were assessed. RESULTS: Between 2005 and 2015 a total of 3797,546 cases of ACS were recorded. The mean age was 69 years and 36% were females. In-hospital mortality was 6.3%, 62% underwent coronary angiography and 42% received percutaneous coronary intervention. In-hospital mortality was highest for patients with ST-elevation MI (12.0%) and lowest for patients with unstable angina pectoris (0.6%). From 2005 to 2015 the incidence rates of ACS, ST-elevation MI and unstable angina pectoris decreased, while the incidence rate of non-ST-elevation MI increased. The percentages of performed coronary angiographies and percutaneous coronary interventions increased from 52 to 70% and 34 to 50%, respectively. The adjusted incidence rate of in-hospital mortality decreased from 64.9 cases per 1000 person-years to 54.8 cases. CONCLUSION: In a large dataset including more than 3.7 million cases, we report an increase in coronary procedures and a reduction of ACS incidence and related mortality in the past decade in Germany.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31925996

RESUMO

BACKGROUND: The Society of Cardiovascular Angiography and Interventions (SCAI) have recently proposed a new classification of cardiogenic shock (CS) dividing patients into five subgroups. OBJECTIVE: Aim of this study was to apply the SCAI classification to a cohort of patients presenting with CS and to evaluate its ability to predict 30-day survival. METHODS: SCAI CS subgroups were interpreted based on the recent consensus statement and then applied to N = 1,007 consecutive patients presenting with CS or large myocardial infarction (MI) between October 2009 and October 2017. The association between SCAI classification and 30-day all-cause mortality was assessed by logistic regression analysis. RESULTS: Mean age in the study cohort was 67 (±15) years, 72% were male. Mean lactate at baseline was 6.05 (±5.13) mmol/l and 51% of the patients had prior cardiac arrest. Overall survival probability was 50.6% (95% confidence interval [CI] 47.5-54.0%). In view of the SCAI classification, the survival probability was 96.4% (95% CI 93.7-99.0%) in class A, 66.1% (95% CI 50.2-87.1%) in class B, 46.1% (95% CI 40.6-52.4%) in class C, 33.1% (95% CI 26.6-41.1%) in class D, and 22.6% (95% CI 17.1-30.0%) in class E. Higher SCAI classification was significantly associated with lower 30-day survival (p < .01). CONCLUSION: In this large clinical cohort, the SCAI classification was significantly associated with 30-day survival. This finding supports the rationale of the SCAI CS classification and calls for a validation in a prospective trial.

3.
Diabetes Care ; 43(2): 460-467, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31843947

RESUMO

OBJECTIVE: Patients with diabetes mellitus (DM) have elevated levels of high-sensitivity cardiac troponin (hs-cTn). We investigated the diagnostic performance of the European Society of Cardiology (ESC) algorithms to rule out or rule in acute myocardial infarction (AMI) without ST-elevation in patients with DM. RESEARCH DESIGN AND METHODS: We prospectively enrolled 3,681 patients with suspected AMI and stratified those by the presence of DM. The ESC 0/1-h and 0/3-h algorithms were used to calculate negative and positive predictive values (NPV, PPV). In addition, alternative cutoffs were calculated and externally validated in 2,895 patients. RESULTS: In total, 563 patients (15.3%) had DM, and 137 (24.3%) of these had AMI. When the ESC 0/1-h algorithm was used, the NPV was comparable in patients with and without DM (absolute difference [AD] -1.50 [95% CI -5.95, 2.96]). In contrast, the ESC 0/3-h algorithm resulted in a significantly lower NPV in patients with DM (AD -2.27 [95% CI -4.47, -0.07]). The diagnostic performance for rule-in of AMI (PPV) was comparable in both groups: 0/1-h (AD 6.59 [95% CI -19.53, 6.35]) and 0/3-h (AD 1.03 [95% CI -7.63, 9.7]). Alternative cutoffs increased the PPV in both algorithms significantly, while improvements in NPV were only subtle. CONCLUSIONS: Application of the ESC 0/1-h algorithm revealed comparable safety to rule out AMI comparing patients with and without DM, while this was not observed with the ESC 0/3-h algorithm. Although alternative cutoffs might be helpful, patients with DM remain a high-risk population in whom identification of AMI is challenging and who require careful clinical evaluation.

4.
Eur Respir J ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831579

RESUMO

Chronic obstructive pulmonary disease (COPD) is a leading cause of death with a considerable part of the population dying from cardiovascular diseases. High-sensitivity troponin I (hs-TnI) might help to better identify COPD patients at high risk of mortality. We aimed to study the predictive value of hs-TnI for all-cause mortality beyond established COPD assessments, and after consideration of relevant cardiovascular risk factors and prevalent cardiovascular diseases, in a broad population with stable COPD.Circulating hs-TnI concentrations together with a wide range of respiratory and cardiovascular markers were evaluated in 2085 patients with stable COPD across all severity stages enrolled in the multi-center COSYCONET cohort study. The primary outcome was all-cause mortality over 3 years of follow-up.Hs-TnI was detectable in 2020 (96.9%) patients. The median hs-TnI concentration was 3.8 ng·L-1 (IQR, 2.5‒6.6 ng·L-1) with levels above the 99th percentile reference limit of 27 ng·L-1 observed in 1.8% patients. In Cox regression analyses including adjustments for airflow limitation, dyspnea grade, exercise capacity, and history of severe exacerbations, as well as traditional cardiovascular risk factors, estimated glomerular filtration rate, ankle-brachial index, N-terminal pro-brain natriuretic peptides, and prevalent cardiovascular diseases, hs-TnI was a significant predictor for all-cause mortality, both as a continuous variable (HR for log hs-TnI, 1.28 [95%CI, 1.01‒1.62]) and categorised according to the cut-off of 6 ng·L-1 (HR, 1.63 [95%CI, 1.10‒2.42]).In patients with stable COPD, hs-TnI is a strong predictor of all-cause mortality beyond established COPD mortality predictors, and independent of a broad range of cardiovascular risk factors and prevalent cardiovascular diseases. Hs-TnI concentrations well-below the upper reference limit provide further prognostic value for all patients with COPD when added to established risk assessments.

6.
Clin Chem ; 65(12): 1592-1601, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31699700

RESUMO

BACKGROUND: Increasing numbers of patients are presenting worldwide to emergency departments with suspected myocardial infarction. The use of point-of-care troponin assays might enable faster decision-making in this high-risk population and reduce the burden on emergency facilities. Here, we evaluate the diagnostic performance of a point-of-care high-sensitivity troponin I assay. METHODS: We conducted a prospective cohort study including patients presenting to the emergency department with suspected myocardial infarction from July 2013 to July 2016. A diagnostic algorithm for a high-sensitivity troponin I point-of-care assay was developed in a derivation data set with 669 patients and validated in an additional 610 patients. RESULTS: The derived 0/1 h algorithm for the point-of-care assay consisted of an admission troponin I <4 ng/L and a δ from 0 h to 1 h <3 ng/L for rule out and an admission troponin I ≥90 ng/L or a δ from 0 h to 1 h ≥20 ng/L for rule in of non-ST-elevation myocardial infarction. Application to the validation cohort showed a negative predictive value of 99.7% (95% CI, 98.1%-100.0%) and 48.0% of patients ruled out, whereas 14.6% were ruled in with a positive predictive value of 86.5% (95% CI, 77.6%-92.8%). The diagnostic performance of the point-of-care high-sensitivity assay was highly comparable to guideline-recommended use of a laboratory-based high-sensitivity troponin assay. CONCLUSIONS: The clinical application of a 0/1 h diagnostic algorithm based on a high-sensitivity troponin I point-of-care assay is safe, and diagnostic performance is comparable to a laboratory-based high-sensitivity troponin I assay.

7.
Biomolecules ; 9(9)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505902

RESUMO

: High-sensitivity troponin has proven to be a promising biomarker for the prediction of future adverse cardiovascular events. We aimed to assess the prognostic value of high-sensitivity troponin I (hs-TnI) on admission in patients with suspected acute myocardial infarction (AMI) analyzed by a novel (Singulex Clarity cTnI) and established hs-TnI assay (ARCHITECT STAT hs-TnI, Abbott). Hs-TnI was measured in a total of 2332 patients from two prospective cohort studies presenting to the emergency department with suspected AMI. The prognostic impact for overall and cardiovascular mortality of both hs-TnI assays was assessed in the total patient cohort as well as in the subgroups of patients with AMI (n = 518) and without AMI (non-AMI) (n = 1814). Patients presenting with highest hs-TnI levels showed higher overall and cardiovascular mortality rates compared to those with lower troponin levels, irrespective of the assay used. Both hs-TnI assays indicated association with overall mortality according to adjusted hazard ratio (HR) among the entire study population (HR for Singulex assay: 1.16 (95% CI 1.08-1.24) and HR for Abbott assay: 1.17 (95% CI 1.09-1.25)). This finding was particularly pronounced in non-AMI patients, whereas no association between hs-TnI and overall mortality was found in AMI patients for either assay. In non-AMI patients, both assays equally improved risk prediction for cardiovascular mortality beyond conventional cardiovascular risk factors. Hs-TnI is independently predictive for adverse outcomes in patients with suspected AMI, especially in the subset of patients without confirmed AMI. There was no difference between the established and the novel assay in the prediction of mortality.

8.
Circulation ; 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31416346

RESUMO

BACKGROUND: Variations in cardiac troponin concentrations by age, sex and time between samples in patients with suspected myocardial infarction are not currently accounted for in diagnostic approaches. We aimed to combine these variables through machine learning to improve the assessment of risk for individual patients. METHODS: A machine learning algorithm (myocardial-ischemic-injury-index [MI3]) incorporating age, sex, and paired high-sensitivity cardiac troponin I concentrations, was trained on 3,013 patients and tested on 7,998 patients with suspected myocardial infarction. MI3 uses gradient boosting to compute a value (0-100) reflecting an individual's likelihood of a diagnosis of type 1 myocardial infarction and estimates the sensitivity, negative predictive value (NPV), specificity and positive predictive value (PPV) for that individual. Assessment was by calibration and area under the receiver-operating-characteristic curve (AUC). Secondary analysis evaluated example MI3 thresholds from the training set that identified patients as low-risk (99% sensitivity) and high-risk (75% PPV), and performance at these thresholds was compared in the test set to the 99th percentile and European Society of Cardiology (ESC) rule-out pathways. RESULTS: Myocardial infarction occurred in 404 (13.4%) patients in the training set and 849 (10.6%) patients in the test set. MI3 was well calibrated with a very high AUC of 0.963 [0.956-0.971] in the test set and similar performance in early and late presenters. Example MI3 thresholds identifying low-risk and high-risk patients in the training set were 1.6 and 49.7 respectively. In the test set, MI3 values were <1.6 in 69.5% with a NPV of 99.7% (99.5%-99.8%) and sensitivity of 97.8% (96.7-98.7%), and were ≥49.7 in 10.6% with a PPV of 71.8% (68.9-75.0%) and specificity of 96.7% (96.3-97.1%). Using these thresholds, MI3 performed better than the ESC 0/3-hour pathway (sensitivity 82.5% [74.5-88.8%], specificity 92.2% [90.7-93.5%]) and the 99th percentile at any time-point (sensitivity 89.6% [87.4-91.6%]), specificity 89.3% [88.6-90.0%]). CONCLUSIONS: Using machine learning, MI3 provides an individualized and objective assessment of the likelihood of myocardial infarction, which can be used to identify low-risk and high-risk patients who may benefit from earlier clinical decisions. CLINICAL TRIAL REGISTRATION: Unique Identifier: Australian New Zealand Clinical Trials Registry: ACTRN12616001441404. URL: https://www.anzctr.org.au.

9.
Jpn J Radiol ; 37(9): 642-650, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301000

RESUMO

PURPOSE: To investigate the effects of renal denervation (RDN) on left ventricular (LV) mass, myocardial strain and diastolic function in patients with treatment-resistant arterial hypertension by cardiac magnet resonance imaging on a 12-month follow-up. MATERIALS AND METHODS: Sixteen patients (38% female) were examined before and 12 months after RDN. LV morphology and strain were analyzed. Diastolic function was determined by early (EPFR) and atrial peak filling rates (APFR) derived from differential volume-time-curve analysis. Clinical visits included 24-h ambulant blood pressure monitoring (ABPM). RESULTS: Twelve months after RDN LV mass decreased from 80 ± 21 g/m2 to 74 ± 20 g/m2 (P < 0.05). Global radial (35 ± 12% vs. 41 ± 10%, P < 0.05) and longitudinal strain improved (- 15 ± 4% vs. - 17 ± 3%, P < 0.05). Global circumferential strain (- 16 ± 5% vs. - 18 ± 4%, P = 0.12) remained unchanged. The parameter of diastolic LV function PFRR (EPFR/APFR) improved following RDN (0.9 ± 0.4 vs. 1.1 ± 0.5, P < 0.05). Individual changes of LV mass were associated with an increase of EPFR (r = - 0.54, P < 0.05) and a reduction of APFR by trend (r = 0.45, P = 0.08). Systolic ABPM showed a decrease by trend (152 mmHg vs. 148 mmHg, P = 0.08). CONCLUSIONS: After RDN we observed a reduction of LV mass, improvement of global strain and diastolic function.


Assuntos
Coração/fisiopatologia , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/complicações , Rim/cirurgia , Imagem por Ressonância Magnética/métodos , Simpatectomia/métodos , Diástole , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/terapia , Rim/inervação , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
10.
Circ Res ; 125(3): 328-340, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31159652

RESUMO

RATIONALE: Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs), are proposed novel biomarkers of myocardial injury. Their release kinetics have not been explored without confounding by heparin nor has their relationship to myocardial protein biomarkers. OBJECTIVE: To compare ncRNA types in heparinase-treated samples with established and emerging protein biomarkers for myocardial injury. METHODS AND RESULTS: Screening of 158 circRNAs and 21 lncRNAs in human cardiac tissue identified 12 circRNAs and 11 lncRNAs as potential biomarkers with cardiac origin. Eleven miRNAs were included. At low spike-in concentrations of myocardial tissue, significantly higher regression coefficients were observed across ncRNA types compared with cardiac troponins and cMyBP-C (cardiac myosin-binding protein C). Heparinase treatment of serial plasma and serum samples of patients undergoing transcoronary ablation of septal hypertrophy removed spurious correlations between miRNAs in non-heparinase-treated samples. After transcoronary ablation of septal hypertrophy, muscle-enriched miRNAs (miR-1 and miR-133a) showed a steeper and earlier increase than cardiac-enriched miRNAs (miR-499 and miR-208b). Putative cardiac lncRNAs, including LIPCAR (long intergenic noncoding RNA predicting cardiac remodeling and survival), did not rise, refuting a predominant cardiac origin. Cardiac circRNAs remained largely undetectable. In a validation cohort of acute myocardial infarction, receiver operating characteristic curve analysis revealed noninferiority of cardiac-enriched miRNAs, but miRNAs failed to identify cases presenting with low troponin values. cMyBP-C was validated as a biomarker with highly sensitive properties, and the combination of muscle-enriched miRNAs with high-sensitive cardiac troponin T and cMyBP-C returned the highest area under the curve values. CONCLUSIONS: In a comparative assessment of ncRNAs and protein biomarkers for myocardial injury, cMyBP-C showed properties as the most sensitive cardiac biomarker while miRNAs emerged as promising candidates to integrate ncRNAs with protein biomarkers. Sensitivity of current miRNA detection is inferior to cardiac proteins but a multibiomarker combination of muscle-enriched miRNAs with cMyBP-C and cardiac troponins could open a new path of integrating complementary characteristics of different biomarker types.

11.
N Engl J Med ; 380(26): 2529-2540, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31242362

RESUMO

BACKGROUND: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. METHODS: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. RESULTS: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. CONCLUSIONS: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.).


Assuntos
Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Medição de Risco/métodos , Troponina/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Troponina I/sangue
12.
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).

13.
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
14.
J Crit Care ; 56: 100-105, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31896442

RESUMO

PURPOSE: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly used treatment option for patients in need of mechanical cardiopulmonary support, while available outcome data is limited. The aim of this study was to identify predictors for 30-day in-hospital mortality. MATERIAL AND METHODS: We analyzed baseline characteristics and outcomes of 8351 VA-ECMO procedures performed in Germany from 2007 to 2015. Using a multivariable model, we identified the ten most important variables to allow for prediction of 30-day in-hospital mortality. Based on these variables, we created a mortality prediction score (ECMO-ACCEPTS score) to enhance decision making in patients considered for or treated with VA-ECMO support. RESULTS: Of 8351 patients (71.7% male) 3567 had prior CPR. Mean age was 62 years in the present cohort. The overall 30-day in-hospital mortality was 61%. The ECMO-ACCEPTS score, derived among randomly selected 4175 patients, included ten independent predictors for in-hospital mortality. Internal validation in the remaining 4176 patients confirmed strong differentiation between low and high risk of 30-day in-hospital mortality (r = 0.97 for correlation of predicted with observed mortality, p < .001). CONCLUSIONS: The ECMO-ACCEPTS score might help clinicians to improve risk prediction among VA-ECMO patients for refractory cardiogenic shock.

16.
J Am Heart Assoc ; 7(19): e008032, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30371308

RESUMO

Background Patients with chronic kidney disease ( CKD ) are at high risk of myocardial infarction. Cardiac troponins are the biomarkers of choice for the diagnosis of acute myocardial infarction ( AMI ) without ST -segment elevation ( NSTE ). In patients with CKD , troponin levels are often chronically elevated, which reduces their diagnostic utility when NSTE - AMI is suspected. The aim of this study was to derive a diagnostic algorithm for serial troponin measurements in patients with CKD and suspected NSTE - AMI . Methods and Results Two cohorts, 1494 patients from a prospective cohort study with high-sensitivity troponin I (hs- cTnI ) measurements and 7059 cases from a clinical registry with high-sensitivity troponin T (hs- cTnT ) measurements, were analyzed. The prospective cohort comprised 280 CKD patients (estimated glomerular filtration rate <60 mL/min/1.73 m2). The registry data set contained 1581 CKD patients. In both cohorts, CKD patients were more likely to have adjudicated NSTE - AMI than non- CKD patients. The specificities of hs- cTnI and hs- cTnT to detect NSTE - AMI were reduced with CKD (0.82 versus 0.91 for hs- cTnI and 0.26 versus 0.73 for hs- cTnT ) but could be restored by applying optimized cutoffs to either the first or a second measurement after 3 hours. The best diagnostic performance was achieved with an algorithm that incorporates serial measurements and rules in or out AMI in 69% (hs- cTnI ) and 55% (hs- cTnT ) of CKD patients. Conclusions The diagnostic performance of high-sensitivity cardiac troponins in patients with CKD with suspected NSTE - AMI is improved by use of an algorithm based on admission troponin and dynamic changes in troponin concentration.


Assuntos
Infarto do Miocárdio/diagnóstico , Insuficiência Renal Crônica/complicações , Troponina I/sangue , Troponina T/sangue , Idoso , Biomarcadores/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia
17.
CMAJ ; 190(33): E974-E984, 2018 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127037

RESUMO

BACKGROUND: Testing for high-sensitivity cardiac troponin (hs-cTn) may assist triage and clinical decision-making in patients presenting to the emergency department with symptoms of acute coronary syndrome; however, this could result in the misclassification of risk because of analytical variation or laboratory error. We sought to evaluate a new laboratory-based risk-stratification tool that incorporates tests for hs-cTn, glucose level and estimated glomerular filtration rate to identify patients at risk of myocardial infarction or death when presenting to the emergency department. METHODS: We constructed the clinical chemistry score (CCS) (range 0-5 points) and validated it as a predictor of 30-day myocardial infarction (MI) or death using data from 4 cohort studies involving patients who presented to the emergency department with symptoms suggestive of acute coronary syndrome. We calculated diagnostic parameters for the CCS score separately using high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT). RESULTS: For the combined cohorts (n = 4245), 17.1% of participants had an MI or died within 30 days. A CCS score of 0 points best identified low-risk participants: the hs-cTnI CCS had a sensitivity of 100% (95% confidence interval [CI] 99.5%-100%), with 8.9% (95% CI 8.1%-9.8%) of the population classified as being at low risk of MI or death within 30 days; the hs-cTnT CCS had a sensitivity of 99.9% (95% CI 99.2%-100%), with 10.5% (95% CI 9.6%-11.4%) of the population classified as being at low risk. The CCS had better sensitivity than hs-cTn alone (hs-cTnI < 5 ng/L: 96.6%, 95% CI 95.0%-97.8%; hs-cTnT < 6 ng/L: 98.2%, 95% CI 97.0%-99.0%). A CCS score of 5 points best identified patients at high risk (hs-cTnI CCS: specificity 96.6%, 95% CI 96.0%-97.2%; 11.2% [95% CI 10.3%-12.2%] of the population classified as being at high risk; hs-cTnT CCS: specificity 94.0%, 95% CI 93.1%-94.7%; 13.1% [95% CI 12.1%-14.1%] of the population classified as being at high risk) compared with using the overall 99th percentiles for the hs-cTn assays (specificity of hs-cTnI 93.2%, 95% CI 92.3-94.0; specificity of hs-cTnT 73.8%, 95% CI 72.3-75.2). INTERPRETATION: The CCS score at the chosen cut-offs was more sensitive and specific than hs-cTn alone for risk stratification of patients presenting to the emergency department with suspected acute coronary syndrome. Study registration: ClinicalTrials.gov, nos. NCT01994577; NCT02355457.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Técnicas de Laboratório Clínico , Miocárdio/química , Troponina I/análise , Troponina T/análise , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Morte , Serviço Hospitalar de Emergência , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo
18.
Hypertension ; 70(4): 743-750, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28784648

RESUMO

Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP. Based on 2 populations including 2549 individuals, a meta-analyses of monocytic transcriptome-wide profiles were performed to identify transcripts associated with BP. Replication was performed in 2 independent studies of whole-blood transcriptome data including 1990 individuals. For identified candidate genes, a direct link between long-term changes in BP and gene expression over time and by treatment with BP-lowering therapy was assessed. The predictive value of protein levels encoded by candidate genes for subsequent cardiovascular disease was investigated. Eight transcripts (CRIP1, MYADM, TIPARP, TSC22D3, CEBPA, F12, LMNA, and TPPP3) were identified jointly accounting for up to 13% (95% confidence interval, 8.7-16.2) of BP variability. Changes in CRIP1, MYADM, TIPARP, LMNA, TSC22D3, CEBPA, and TPPP3 expression associated with BP changes-among these, CRIP1 gene expression was additionally correlated to measures of cardiac hypertrophy. Assessment of circulating CRIP1 (cystein-rich protein 1) levels as biomarkers showed a strong association with increased risk for incident stroke (hazard ratio, 1.06; 95% confidence interval, 1.03-1.09; P=5.0×10-5). Our comprehensive analysis of global gene expression highlights 8 novel transcripts significantly associated with BP, providing a link between gene expression and BP. Translational approaches further established evidence for the potential use of CRIP1 as emerging disease-related biomarker.


Assuntos
Proteínas de Transporte/genética , Hipertensão , Proteínas com Domínio LIM/genética , Acidente Vascular Cerebral , Adulto , Pressão Sanguínea/genética , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/estatística & dados numéricos , Proteínas Estimuladoras de Ligação a CCAAT/genética , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/diagnóstico , Hipertensão/genética , Masculino , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina/genética , Poli(ADP-Ribose) Polimerases/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fatores de Transcrição/genética
19.
J Immunol ; 191(9): 4531-9, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24062488

RESUMO

Multiple sclerosis is considered to be initiated by a deregulated, myelin-specific T cell response. However, the formation of inflammatory CNS lesions and the contribution of different leukocyte subsets in setting up these lesions are still incompletely understood. In this study, we show that, in the mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis, neutrophil granulocytes are important contributors in preparing CNS inflammation. Preclinical single-dose Ab-mediated depletion of neutrophils delayed the onset and continuous depletion attenuated the development of experimental autoimmune encephalomyelitis, whereas the generation of a myelin-specific T cell response remained unaffected. Neutrophil-related enzymes such as myeloperoxidase and neutrophil elastase did not contribute in mounting CNS inflammation, as analyzed by using respective knockout mice and inhibitors. CNS-infiltrating neutrophils secreted proinflammatory molecules and matured bone marrow-derived dendritic cells in vitro, which in turn enhanced their ability to restimulate myelin-specific T cells. This was mirrored in vivo, in which depletion of neutrophils specifically impaired maturation of microglia and macrophages into professional APCs, resulting in a diminished amplification of early CNS inflammation. Therefore, inside the CNS neutrophils provide local cofactors that are required for the maturation of myeloid cells into professional APCs representing an essential step for the local restimulation of myelin-specific T cells and the development of autoimmune disease.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Sistema Nervoso Central/imunologia , Células Dendríticas/imunologia , Encefalomielite Autoimune Experimental/imunologia , Neutrófilos/imunologia , Linfócitos T/imunologia , Animais , Apresentação do Antígeno/imunologia , Autoimunidade/imunologia , Células Cultivadas , Citocinas/metabolismo , Inflamação/imunologia , Elastase de Leucócito/genética , Elastase de Leucócito/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/imunologia , Microglia/metabolismo , Esclerose Múltipla/imunologia , Peroxidase/genética , Peroxidase/metabolismo
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