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BACKGROUND: Sodium-induced microcirculatory changes, endothelial surface layer alterations in particular, may play an important role in sodium-mediated blood pressure elevation. However, effects of acute and chronic sodium loading on the endothelial surface layer and microcirculation in humans have not been established. The objective of this study was to assess sodium-induced changes in blood pressure and body weight as primary outcomes and also in microvascular permeability, sublingual microcirculatory dimensions, and urinary glycosaminoglycan excretion in healthy subjects. METHODS: Twelve normotensive males followed both a low-sodium diet (less than 50 mmol/day) and a high-sodium diet (more than 200 mmol/day) for eight days in randomized order, separated by a crossover period. After the low-sodium diet, hypertonic saline (5 mmol sodium/liter body water) was administered intravenously in 30 min. RESULTS: Both sodium interventions did not change blood pressure. Body weight increased with 2.5 (95% CI, 1.7 to 3.2) kg (P < 0.001) after dietary sodium loading. Acute intravenous sodium loading resulted in increased transcapillary escape rate of I-labeled albumin (2.7 [0.1 to 5.3] % cpm · g · h; P = 0.04), whereas chronic dietary sodium loading did not affect transcapillary escape rate of I-labeled albumin (-0.03 [-3.3 to 3.2] % cpm · g · h; P = 1.00), despite similar increases of plasma sodium and osmolality. Acute intravenous sodium loading coincided with significantly increased plasma volume, as assessed by the distribution volume of albumin, and significantly decreased urinary excretion of heparan sulfate and chondroitin sulfate. These changes were not observed after dietary sodium loading. CONCLUSIONS: Our results suggest that intravenous sodium loading has direct adverse effects on the endothelial surface layer, independent of blood pressure.
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Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Permeabilidad Capilar/efectos de los fármacos , Microcirculación/efectos de los fármacos , Sodio en la Dieta/farmacología , Adolescente , Adulto , Estudios Cruzados , Glicosaminoglicanos/orina , Humanos , Masculino , Solución Salina Hipertónica/administración & dosificación , Sodio en la Dieta/administración & dosificación , Sodio en la Dieta/orina , Adulto JovenRESUMEN
Aims: Galectin-3 (Gal-3) is an important mediator of cardiac fibrosis, particularly in heart failure. Increased Gal-3 concentration (Gal-3), associated with increased risk of developing atrial fibrillation (AF), may reflect atrial fibrotic remodelling underlying AF progression. We aimed to investigate whether the change in serum Gal-3 reflects alterations of the arrhythmogenic atrial substrate following thoracoscopic AF surgery, and predicts absence of AF. Methods and results: Consecutive patients undergoing thoracoscopic AF surgery were included. Left atrial appendages (LAAs) and serum were collected during surgery and serum again 6 months thereafter. Gal-3 was determined in tissue and serum. Interstitial collagen in the LAA was quantified using Picrosirius red staining. Ninety-eight patients (76% male, mean age 60 ± 9 years) underwent thoracoscopic surgery for advanced AF. Patients with increased Gal-3 after ablation compared to baseline had a higher recurrence rate compared to patients with decreased or unchanged Gal-3 (HR 2.91, P = 0.014). These patients more frequently had persistent AF, longer AF duration and thick atrial collagen strands (P = 0.049). At baseline, Gal-3 was similar between patients with and without AF recurrence: 14.8 ± 3.9 µg/L vs. 13.7 ± 3.7 µg/L, respectively in serum (P = 0.16); 94.5 ± 19.4 µg/L vs. 93.3 ± 30.8µg/L, respectively in atrial myocardium (P = 0.83). There was no correlation between serum Gal-3 and left atrial Gal-3 (P = 0.20), nor between serum Gal-3 and the percentage of fibrosis in LAA (P = 0.18). Conclusion: The change of circulating Gal-3, rather than its baseline value, predicts AF recurrence after thoracoscopic ablation. Patients in whom Gal-3 increases after ablation have a high recurrence rate reflecting ongoing profibrotic signalling, irrespective of arrhythmia continuation.
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Fibrilación Atrial , Galectina 3/sangre , Atrios Cardíacos , Toracoscopía , Anciano , Apéndice Atrial/patología , Apéndice Atrial/cirugía , Fibrilación Atrial/sangre , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/patología , Remodelación Atrial/fisiología , Electrocardiografía/métodos , Femenino , Fibrosis , Estudios de Seguimiento , Atrios Cardíacos/patología , Atrios Cardíacos/cirugía , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Recurrencia , Reproducibilidad de los Resultados , Toracoscopía/efectos adversos , Toracoscopía/métodosRESUMEN
BACKGROUND: We have previously shown that older thrombus is associated with a twofold higher long-term mortality in ST-segment elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (pPCI). We evaluated whether the addition of the presence of older thrombus to a multimarker model would result in increased predictive power for 1-year mortality in STEMI patients. METHODS: The study population (n = 1442) consists of STEMI patients treated with thrombus aspiration during pPCI. Patients were included if aspirated thrombus material could histopathologically be classified according to thrombus age (n = 870) and laboratory measurements of biomarkers (cardiac troponin T, glucose, N-terminal pro-brain natriuretic peptide, estimated glomerular filtration rate and C-reactive protein) were available. The additional prognostic value of the presence of older thrombus beyond multiple biomarkers and established clinical risk factors was evaluated using multivariate Cox regression models. RESULTS: Serum biomarker concentrations were similar between patients with fresh and older thrombus. Sixty patients (7%) died within 1 year. The presence of older thrombus remained strongly associated with mortality at 1 year after multivariable adjustment for multiple biomarkers and established clinical risk factors. Addition of older thrombus to either a model including clinical risk factors and biomarkers or a model including solely biomarkers resulted in significant increases in the discriminative value, evidenced by net reclassification improvement and integrated discriminative improvement. CONCLUSIONS: The presence of older thrombus provides independent complementary information to a multimarker model including established clinical risk factors and multiple biomarkers for predicting 1-year mortality in STEMI patients treated with pPCI and thrombus aspiration.
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Mortalidad , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST/cirugía , Trombectomía , Trombosis/cirugía , Anciano , Proteína C-Reactiva/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Pronóstico , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/epidemiología , Trombosis/epidemiología , Trombosis/patología , Factores de Tiempo , Troponina T/sangreRESUMEN
Unfractionated heparin (UFH) plasma protein binding and elimination might be impaired in patients with chronic kidney disease (CKD-defined as creatinine clearance <60 ml/min). It is currently unknown at which UFH bolus dose persistent prolongation of activated partial thromboplastin time (aPTT) occurs in ST-segment elevation myocardial infarction (STEMI) patients with CKD. We investigated the effect of different UFH bolus doses on the first aPTT measured within 6 and 12 h after PPCI in 1071 STEMI patients with and without CKD undergoing primary percutaneous coronary intervention (PPCI) between 1-1-2003 and 31-07-2008. In the first 6 h after PPCI, aPTT ratio was 5.1 for patients with CKD versus 3.4 for those without (p < 0.001). The proportion of patients with markedly high aPTTs (aPTT ratio ≥ 4 times control) increased with increasing heparin bolus and beyond 130 IU/kg there was a marked difference between patients with and without CKD (74.1 and 42.3 % respectively, p < 0.001). By multivariable analysis, CKD was associated with an increased risk of markedly high aPTTs (odds ratio (OR) 2.04; 95 % confidence interval (CI) 1.27-3.27), driven largely by an increased risk of aPTT prolongation in patients treated with UFH boluses ≥130 IU/kg (OR 3.69; 95 % CI 1.85-7.36; p for interaction = 0.009). In conclusion, CKD is associated with severe persistent aPTT prolongation in STEMI patients undergoing PPCI, possibly due to impaired plasma protein binding and reduced UFH elimination. A lower heparin bolus dose might result in lower aPTTs and less bleeding complications in patients with CKD undergoing PPCI.
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Heparina , Infarto del Miocardio , Intervención Coronaria Percutánea/efectos adversos , Hemorragia Posoperatoria/sangre , Insuficiencia Renal Crónica , Anciano , Anciano de 80 o más Años , Femenino , Heparina/administración & dosificación , Heparina/efectos adversos , Heparina/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/cirugía , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/cirugíaRESUMEN
BACKGROUND: Serum levels of N-terminal proB-type natriuretic peptide (NT-proBNP) are elevated in patients acute respiratory distress syndrome (ARDS). Recent studies showed a lower incidence of acute cor pulmonale in ARDS patients ventilated with lower tidal volumes. Consequently, serum levels of NT-proBNP may be lower in these patients. We investigated the relation between serum levels of NT-proBNP and tidal volumes in critically ill patients without ARDS at the onset of mechanical ventilation. METHODS: Secondary analysis of a randomized controlled trial of lower versus conventional tidal volumes in patients without ARDS. NT-pro BNP were measured in stored serum samples. Serial serum levels of NT-pro BNP were analyzed controlling for acute kidney injury, cumulative fluid balance and presence of brain injury. The primary outcome was the effect of tidal volume size on serum levels of NT-proBNP. Secondary outcome was the association with development of ARDS. RESULTS: Samples from 150 patients were analyzed. No relation was found between serum levels of NT-pro BNP and tidal volume size. However, NT-proBNP levels were increasing in patients who developed ARDS. In addition, higher levels were observed in patients with acute kidney injury, and in patients with a more positive cumulative fluid balance. CONCLUSION: Serum levels of NT-proBNP are independent of tidal volume size, but are increasing in patients who develop ARDS.
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Enfermedad Crítica , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Respiración Artificial , Síndrome de Dificultad Respiratoria/epidemiología , Volumen de Ventilación Pulmonar/fisiología , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Síndrome de Dificultad Respiratoria/sangre , Factores de Riesgo , Índice de Severidad de la Enfermedad , Equilibrio HidroelectrolíticoRESUMEN
BACKGROUND: The multimarker risk score, based on estimated glomerular filtration rate, glucose, and N-terminal probrain natriuretic peptide (NT-proBNP), has been shown to predict mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). In this study, we investigated the relation between the multimarker risk score and cardiovascular mechanistic markers of outcomes in STEMI patients undergoing PPCI. METHODS: Complete biomarkers were available in 197 patients with STEMI. Angiographic Thrombolysis In Myocardial Infarction flow grade and myocardial blush grade at the end of the PPCI, electrocardiographic ST-segment resolution (STR) at the time of last contrast injection and 240 minutes after last contrast, and cardiac magnetic resonance (CMR) left ventricular ejection fraction (LVEF) and infarct size at 4 to 6 months after the index event were available. RESULTS: In linear regression models, higher multimarker scores were associated with worse angiographic (P < .01 for both outcomes), electrocardiographic (P < .001 for the association with STR at last contrast, and P < .01 for STR at 240 minutes), and CMR outcomes (P < .01 for both). CONCLUSIONS: The multimarker risk score is associated with angiographic, electrocardiographic, and CMR mechanistic markers of outcomes. These data support the ability of the multimarker risk score to identify patients at high risk for suboptimal reperfusion and CMR outcomes and may aid in the early triage of patients who stand to benefit most of adjuvant treatments in STEMI.
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Angioplastia Coronaria con Balón/métodos , Angiografía Coronaria/métodos , Electrocardiografía/métodos , Imagen por Resonancia Magnética/métodos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Angioplastia Coronaria con Balón/mortalidad , Infarto de la Pared Anterior del Miocardio/diagnóstico , Infarto de la Pared Anterior del Miocardio/mortalidad , Infarto de la Pared Anterior del Miocardio/terapia , Biomarcadores/análisis , Biomarcadores/metabolismo , Glucemia/análisis , Estudios de Cohortes , Intervalos de Confianza , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Péptido Natriurético Encefálico/análisis , Admisión del Paciente , Fragmentos de Péptidos/análisis , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Volumen Sistólico , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Monitoring of renal function becomes increasingly important in the aging population of HIV-1 infected patients. We compared Cockroft & Gault (C&G), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD), Cystatin C- and 24 h urine-based estimated GFR (eGFR) with the gold standard, measured GFR (mGFR) using [125I]-iothalamate. METHODS: Substudy within a randomized, multinational trial comparing continuing zidovudine/ lamivudine with switching to tenofovir/ emtricitabine in patients with suppressed HIV-1 infection. Accuracy (defined as the mean difference between eGFR and mGFR) and precision (defined as standard deviation (SD) of the mean difference between eGFR and mGFR) of the eGFRs were calculated using linear regression and Bland & Altman analysis. RESULTS: We included 19 patients, 18 men, 15 Caucasian, mean (SD) age 46.0 y (± 8.9) and BMI 23.9 kg/m2 (± 3.0). Mean (SD) mGFR was 102 ml/min/1.73 m2 (± 19), 4 patients had mild renal dysfunction. All eGFRs tended to underestimate true GFR, with best accuracy for C&G (-1 ml/min/1.73 m2), CKD-EPI (-1 ml/min/1.73 m2), 24 hcreatinine clearance (-2 ml/min/1.73 m2) and MDRD-6 (0 ml/min/1.73 m2), and worst for cystatin C-based (-9 ml/min/1.73 m2) and MDRD-4 estimations (-10 ml/min/1.73 m2). Accuracy worsened at higher mGFR, but was not significantly influenced by age. C&G tended to overestimate at higher BMI. Precision was comparable for all GFR estimations. CONCLUSIONS: In this limited number of patients with preserved renal function and suppressed HIV-infection C&G and CKD-EPI appeared to be the best reflection of real GFR and most practical tool for monitoring GFR.
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Fármacos Anti-VIH/uso terapéutico , Tasa de Filtración Glomerular , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/fisiopatología , Adenina/análogos & derivados , Adenina/uso terapéutico , Adulto , Índice de Masa Corporal , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Emtricitabina , Femenino , Humanos , Lamivudine/uso terapéutico , Modelos Lineales , Masculino , Persona de Mediana Edad , Países Bajos , Organofosfonatos/uso terapéutico , Proyectos Piloto , Proyectos de Investigación , Estadísticas no Paramétricas , Tenofovir , Resultado del Tratamiento , Zidovudina/uso terapéuticoRESUMEN
BACKGROUND: We assessed the value of cystatin C for improvement of risk stratification in patients with non-ST elevation acute coronary syndrome (nSTE-ACS) and increased cardiac troponin T (cTnT), and we compared the long-term effects of an early invasive treatment strategy (EIS) with a selective invasive treatment strategy (SIS) with regard to renal function. METHODS: Patients (n = 1128) randomized to an EIS or an SIS in the ICTUS trial were stratified according to the tertiles of the cystatin C concentration at baseline. The end points were death within 4 years and spontaneous myocardial infarction (MI) within 3 years. RESULTS: Mortality was 3.4%, 6.2%, and 13.5% in the first, second, and third tertiles, respectively, of cystatin C concentration (log-rank P < 0.001), and the respective rates of spontaneous MI were 5.5%, 7.5%, and 9.8% (log-rank P = 0.03). In a multivariate Cox regression analysis, the cystatin C concentration in the third quartile remained independently predictive of mortality [hazard ratio (HR), 2.04; 95% CI, 1.02-4.10; P = 0.04] and spontaneous MI (HR, 1.95; 95% CI, 1.05-3.63; P = 0.04). The mortality rate in the second tertile was lower with the EIS than with the SIS (3.8% vs 8.7%). In the third tertile, the mortality rates with the EIS and the SIS were, respectively, 15.0% and 12.2% (P for interaction = 0.04). Rates of spontaneous MI were similar for the EIS and the SIS within cystatin C tertiles (P for interaction = 0.22). CONCLUSIONS: In patients with nSTE-ACS and an increased cTnT concentration, mild to moderate renal dysfunction is associated with a higher risk of death and spontaneous MI. Use of cystatin C as a serum marker of renal function may improve risk stratification.
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Síndrome Coronario Agudo/sangre , Cistatina C/sangre , Troponina T/sangre , Síndrome Coronario Agudo/terapia , Anciano , Angiografía Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de RiesgoRESUMEN
BACKGROUND: New evidence has emerged that the assessment of multiple biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS) provides unique prognostic information. The purpose of this study was to assess the association between baseline NT-proBNP levels and outcome in patients who have nSTE-ACS with an elevated cTnT and to determine whether patients with elevated NT-proBNP levels benefit from an early invasive treatment strategy. METHODS: Baseline samples for NT-proBNP measurements were available in 1141 patients who have nSTE-ACS with an elevated cTnT randomized to an early or a selective invasive strategy. Patients were followed-up for the occurrence of death, myocardial infarction (MI), and rehospitalization for angina. RESULTS: We showed that increased levels of NT-proBNP were associated with several indicators of risk and severe coronary artery disease. Mortality by 1 year was 7.3% in the highest quartile (> or = 1170 ng/L for men, > or = 2150 ng/L for women) compared with 1.1% of patients in the lower 3 quartiles (P < .0001). N-terminal pro-brain natriuretic peptide (highest quartile vs lower 3 quartiles) was a strong independent predictor of mortality (hazard ratio 5.0, 95% CI 2.1-11.6, P = .0002). However, NT-proBNP levels were not associated with the incidence of recurrent MI by 1 year. Furthermore, we could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy in patients with an elevated NT-proBNP level. CONCLUSIONS: We confirmed that NT-proBNP is a strong independent predictor of mortality by 1 year but not of recurrent MI in patients who have nSTE-ACS with an elevated cTnT. We could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy.
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Angina Inestable/sangre , Angina Inestable/cirugía , Infarto del Miocardio/sangre , Infarto del Miocardio/cirugía , Enfermedad Aguda , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo/métodos , Síndrome , Resultado del TratamientoRESUMEN
INTRODUCTION: Major depressive disorder (MDD) is widely prevalent and severely disabling, mainly due to its recurrent nature. A better understanding of the mechanisms underlying MDD-recurrence may help to identify high-risk patients and to improve the preventive treatment they need. MDD-recurrence has been considered from various levels of perspective including symptomatology, affective neuropsychology, brain circuitry and endocrinology/metabolism. However, MDD-recurrence understanding is limited, because these perspectives have been studied mainly in isolation, cross-sectionally in depressed patients. Therefore, we aim at improving MDD-recurrence understanding by studying these four selected perspectives in combination and prospectively during remission. METHODS AND ANALYSIS: In a cohort design, we will include 60 remitted, unipolar, unmedicated, recurrent MDD-participants (35-65 years) with ≥ 2 MDD-episodes. At baseline, we will compare the MDD-participants with 40 matched controls. Subsequently, we will follow-up the MDD-participants for 2.5 years while monitoring recurrences. We will invite participants with a recurrence to repeat baseline measurements, together with matched remitted MDD-participants. Measurements include questionnaires, sad mood-induction, lifestyle/diet, 3 T structural (T1-weighted and diffusion tensor imaging) and blood-oxygen-level-dependent functional MRI (fMRI) and MR-spectroscopy. fMRI focusses on resting state, reward/aversive-related learning and emotion regulation. With affective neuropsychological tasks we will test emotional processing. Moreover, we will assess endocrinology (salivary hypothalamic-pituitary-adrenal-axis cortisol and dehydroepiandrosterone-sulfate) and metabolism (metabolomics including polyunsaturated fatty acids), and store blood for, for example, inflammation analyses, genomics and proteomics. Finally, we will perform repeated momentary daily assessments using experience sampling methods at baseline. We will integrate measures to test: (1) differences between MDD-participants and controls; (2) associations of baseline measures with retro/prospective recurrence-rates; and (3) repeated measures changes during follow-up recurrence. This data set will allow us to study different predictors of recurrence in combination. ETHICS AND DISSEMINATION: The local ethics committee approved this study (AMC-METC-Nr.:11/050). We will submit results for publication in peer-reviewed journals and presentation at (inter)national scientific meetings. TRIAL REGISTRATION NUMBER: NTR3768.
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Encéfalo/fisiopatología , Trastorno Depresivo Mayor/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Imagen por Resonancia Magnética/métodos , Proyectos de Investigación , Adulto , Anciano , Estudios de Casos y Controles , Estudios Transversales , Humanos , Modelos Lineales , Estudios Longitudinales , Espectroscopía de Resonancia Magnética , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , RecurrenciaRESUMEN
OBJECTIVES: We prospectively studied the prognostic value of predischarge dobutamine stress echocardiography (DSE) in low-risk chest pain patients with a normal or nondiagnostic electrocardiogram (ECG) and a negative serial troponin T. BACKGROUND: Noninvasive stress testing is recommended before discharge or within 72 h in patients with low-risk chest pain. The prognostic value of immediate DSE has not been studied in a blinded, prospective fashion. METHODS: Patients presenting at the emergency room within 6 h of symptom onset and a normal or nondiagnostic ECG were eligible. Dobutamine stress echocardiography was performed after unstable coronary artery disease was ruled out by a standard rule-out protocol and a negative serial troponin T; the occurrence of any new wall motion abnormality was considered positive. Results were kept blinded. End points were cardiac death, myocardial infarction, rehospitalization for unstable angina or revascularization. RESULTS: In total, 377 patients were included. There were 2 deaths, 2 myocardial infarctions, 8 rehospitalization for unstable angina, and 10 revascularizations at six-month follow-up. The end points occurred in 8/26 (30.8%) patients with a positive versus 14/351 (4.0%) patients with a negative DSE (odds ratio, 10.7; 95% confidence interval, 4.0 to 28.8; p < 0.0001). By multivariate analysis, DSE remained a predictor of end points (p < 0.0001). CONCLUSIONS: A predischarge DSE had important, independent prognostic value in low-risk, troponin negative, chest pain patients.
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Angina de Pecho/sangre , Angina de Pecho/diagnóstico por imagen , Ecocardiografía de Estrés , Troponina T/sangre , Adulto , Anciano , Angina de Pecho/fisiopatología , Estudios de Cohortes , Método Doble Ciego , Electrocardiografía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Pronóstico , Estudios Prospectivos , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
BACKGROUND: Quantitative proteomic analysis with mass spectrometry holds great promise for simultaneously quantifying proteins in various biosamples, such as human plasma. Thus far, studies addressing the reproducible measurement of endogenous protein concentrations in human plasma have focussed on targeted analyses employing isotopically labelled standards. Non-targeted proteomics, on the other hand, has been less employed to this end, even though it has been instrumental in discovery proteomics, generating large datasets in multiple fields of research. RESULTS: Using a non-targeted mass spectrometric assay (LCMSE), we quantified abundant plasma proteins (43 mg/mL-40 ug/mL range) in human blood plasma specimens from 30 healthy volunteers and one blood serum sample (ProteomeXchange: PXD000347). Quantitative results were obtained by label-free mass spectrometry using a single internal standard to estimate protein concentrations. This approach resulted in quantitative results for 59 proteins (cut off ≥11 samples quantified) of which 41 proteins were quantified in all 31 samples and 23 of these with an inter-assay variability of ≤ 20%. Results for 7 apolipoproteins were compared with those obtained using isotope-labelled standards, while 12 proteins were compared to routine immunoassays. Comparison of quantitative data obtained by LCMSE and immunoassays showed good to excellent correlations in relative protein abundance (r = 0.72-0.96) and comparable median concentrations for 8 out of 12 proteins tested. Plasma concentrations of 56 proteins determined by LCMSE were of similar accuracy as those reported by targeted studies and 7 apolipoproteins quantified by isotope-labelled standards, when compared to reference concentrations from literature. CONCLUSIONS: This study shows that LCMSE offers good quantification of relative abundance as well as reasonable estimations of concentrations of abundant plasma proteins.
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Proteínas Sanguíneas/análisis , Espectrometría de Masas/métodos , Proteoma/análisis , Proteómica/métodos , Cromatografía Liquida , Voluntarios Sanos , Humanos , Inmunoensayo , Marcaje Isotópico , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: To assess the prognostic value of markers of inflammation for rule-out purposes in patients admitted to the emergency department with troponin T-negative chest pain. METHODS: Patients presenting to the emergency department within 6 hours of symptom onset and who had a normal or nondiagnostic electrocardiogram were eligible. The standard rule-out protocol, which included serial creatine kinase and creatine kinase-MB measurements, was applied, and markers of inflammation (C-reactive protein, erythrocyte sedimentation rate, and total white blood cell count and differential count) were measured. The study group comprised patients with negative serial troponin T results (<0.06 microg/L) who were discharged home after unstable coronary artery disease was ruled out. Endpoints during the 6-month follow-up were cardiac death, myocardial infarction, or rehospitalization for unstable angina. RESULTS: A total of 382 troponin T-negative patients were discharged, of whom 2 died, 2 had a myocardial infarction, and 7 were rehospitalized for unstable angina. A positive C-reactive protein test result (>0.3 mg/dL) was associated with future clinical events (hazard risk [HR] = 4.5; 95% confidence interval [CI]: 1.2 to 17.0; P = 0.03), as was a positive test (>13 mm/h) for erythrocyte sedimentation rate (HR = 5.6; 95% CI: 1.5 to 22.2; P = 0.01). Patients with positive results for both tests were at highest risk of clinical events (9.3%) compared with patients with other combinations of test results (1.1% to 2.1%; HR = 7.5; 95% CI: 2.2 to 25.5; P = 0.001). CONCLUSION: The combination of C-reactive protein and erythrocyte sedimentation rate had prognostic value in patients with troponin T-negative chest pain and a normal or nondiagnostic electrocardiogram in whom unstable coronary artery disease was ruled out.
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Dolor en el Pecho/etiología , Enfermedad Coronaria/diagnóstico , Anciano , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Servicio de Urgencia en Hospital , Femenino , Humanos , Recuento de Leucocitos , Masculino , Pronóstico , Medición de RiesgoRESUMEN
PURPOSE: We investigated the associations between baseline C-reactive protein levels in patients undergoing percutaneous coronary angioplasty and death, nonfatal myocardial infarction, and repeat revascularization during 14 months of follow-up. METHODS: In a single-center, prospective, cohort study, plasma levels of C-reactive protein were measured in 1458 consecutive patients undergoing elective or urgent coronary angioplasty. Patients were followed at 12 to 14 months for the occurrence of death, nonfatal myocardial infarction, and repeat revascularization. RESULTS: The incidence of death or myocardial infarction was 6.1% (44/716) in patients with an increased C-reactive protein level (>3 mg/L) and 1.5% (11/742) in patients with a normal level (relative risk [RR] = 4.4; 95% confidence interval [CI]: 2.2 to 8.5; P <0.0001). In a multivariate logistic regression model, an increased C-reactive protein level was an independent predictor of death or nonfatal myocardial infarction (RR = 3.6; 95% CI: 1.8 to 7.2; P =0.0001). The incidence of repeat revascularization was similar in patients with or without an increased C-reactive protein level (23% [168/716] vs. 22% [163/742], P = 0.54). Statin therapy at the time of the procedure was associated with a lower mean (+/- SD) C-reactive protein level (5.8 +/- 9.7 mg/L vs. 7.2 +/- 12.1 mg/L, P =0.02), but was not associated with the risk of death, nonfatal myocardial infarction, and repeat revascularization during follow-up. CONCLUSION: An increased C-reactive protein level is an independent prognostic indicator for the occurrence of death or nonfatal myocardial infarction following coronary angioplasty, but is not associated with the need for repeat revascularization.
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Angioplastia Coronaria con Balón/estadística & datos numéricos , Proteína C-Reactiva/análisis , Infarto del Miocardio/epidemiología , Distribución por Edad , Biomarcadores/sangre , Estudios de Cohortes , Comorbilidad , Diabetes Mellitus/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipertensión/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Países Bajos/epidemiología , Estudios Prospectivos , Reoperación/estadística & datos numéricos , Factores de Riesgo , Distribución por Sexo , Fumar/epidemiología , Tasa de Supervivencia , Tiempo , Resultado del TratamientoRESUMEN
B-type natriuretic peptide (BNP) and the N-terminus of pro-BNP (NT-pro-BNP) have prognostic value in patients with heart failure and patients with acute coronary syndromes. Little is known about the prognostic value of baseline NT-pro-BNP alone or in combination with C-reactive protein (CRP) for clinical outcome after percutaneous coronary intervention (PCI). Within a single center registry of contemporaneous PCI, we investigated the prognostic value of baseline plasma NT-pro-BNP and CRP concentrations for the prediction of death or nonfatal myocardial infarction (MI) during 12 to 14 months of follow-up. Among 1,172 consecutive patients, the occurrence of death or MI increased significantly with baseline NT-pro-BNP before PCI (first quartile 0 of 294, second quartile 6 of 291 [2.1%], third quartile 4 of 294 [1.4%], fourth quartile 22 of 293 [7.5%)]; p <0.0001). NT-pro-BNP in the top quartile significantly predicted death (odds ratio [OR] 13.37, 95% confidence interval [CI] 4.50 to 40.38, p <0.0001) and was associated with nonfatal MI (OR 2.53, 95% CI 0.77 to 8.34, p = 0.22) An abnormal CRP was significantly associated with death (OR 3.47, 95% CI 1.26 to 9.54, p = 0.019). Stepwise multivariate logistic regression analysis identified age >65 years and NT-pro-BNP as independent significant predictors of death/MI (age OR 3.18, 95% CI 1.32 to 7.67, p = 0.01; NT-pro-BNP OR 4.57, 95% CI 2.07 to 10.10, p = 0.0001). Baseline NT-pro-BNP before PCI provides important, independent prognostic information for the occurrence of death or nonfatal MI during long-term follow-up.
Asunto(s)
Angioplastia Coronaria con Balón , Biomarcadores/sangre , Infarto del Miocardio/sangre , Infarto del Miocardio/mortalidad , Proteínas del Tejido Nervioso/sangre , Fragmentos de Péptidos/sangre , Anciano , Proteína C-Reactiva/análisis , Femenino , Humanos , Masculino , Péptido Natriurético Encefálico , Pronóstico , Análisis de RegresiónRESUMEN
This study is the first that combines a serum marker of inflammation (C-reactive protein) and intracoronary-derived fractional flow reserve. A low C-reactive protein level was strongly associated with uncomplicated follow-up in patients with hemodynamic nonsignificant coronary lesions. These results show that C-reactive protein provides additional information relevant for clinical decision-making in patients with intermediate (30% to 70%) coronary lesions.
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Angina de Pecho/sangre , Angina de Pecho/fisiopatología , Volumen Sanguíneo , Proteína C-Reactiva/análisis , Estenosis Coronaria/sangre , Estenosis Coronaria/fisiopatología , Reproducibilidad de los Resultados , Anciano , Angina de Pecho/terapia , Angioplastia Coronaria con Balón , Estudios de Cohortes , Estenosis Coronaria/terapia , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Valor Predictivo de las Pruebas , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: No five-year long-term follow-up data is available regarding the prognostic value of GDF-15. Our aim is to evaluate the long-term prognostic value of admission growth-differentiation factor 15 (GDF-15) regarding death or myocardial infarction (MI) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: This is a subanalysis from the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial, including troponin positive NSTE-ACS patients. The main outcome for the current analysis was 5-year death or spontaneous MI. GDF-15 samples were available in 1151 patients. The prognostic value of GDF-15, categorized into <1200 ng/L, 1200-1800 ng/L and >1800 ng/L, was assessed in unadjusted and adjusted Cox regression models. Adjustments were made for identified univariable risk factors. The additional discriminative and reclassification value of GDF-15 beyond the independent risk factors was assessed by the category-free net reclassification improvement (1/2 NRI(>0)) and the integrated discrimination improvement (IDI) RESULTS: Compared to GDF-15<1200 ng/L, a GDF-15>1800 ng/L was associated with an increased hazard ratio for death or spontaneous MI, mainly driven by mortality. GDF-15 levels were predictive after adjustments for other identified predictors. Additional discriminative value was shown with the IDI, not with the NRI. CONCLUSION: In patients presenting with NSTE-ACS and elevated troponin T, GDF-15 provides prognostic information in addition to identified predictors for mortality and spontaneous MI and can be used to identify patients at high risk during long-term follow-up.
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Síndrome Coronario Agudo/sangre , Factor 15 de Diferenciación de Crecimiento/sangre , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/terapia , Anciano , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Infarto del Miocardio/terapia , Pronóstico , Factores de Riesgo , Resultado del Tratamiento , Troponina T/sangreRESUMEN
BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is a biomarker predicting cardiovascular diseases in a real-world. However, the prognostic value in patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI) on long-term clinical outcomes is unknown. METHODS: Lp-PLA2 activity was measured in samples obtained prior to pPCI from consecutive STEMI patients in a high-volume intervention center from 2005 until 2007. Five years all-cause mortality was estimated with the Kaplan-Meier method and compared among tertiles of Lp-PLA2 activity during complete follow-up and with a landmark at 30 days. In a subpopulation clinical endpoints were assessed at three years. The prognostic value of Lp-PLA2, in addition to the Thrombolysis In Myocardial Infarction or multimarker risk score, was assessed in multivariable Cox regression. RESULTS: The cohort (n = 987) was divided into tertiles (low <144, intermediate 144-179, and high >179 nmol/min/mL). Among the tertiles differences in baseline characteristics associated with long-term mortality were observed. However, no significant differences in five years mortality in association with Lp-PLA2 activity levels were found; intermediate versus low Lp-PLA2 (HR 0.97; CI 95% 0.68-1.40; p = 0.88) or high versus low Lp-PLA2 (HR 0.75; CI 95% 0.51-1.11; p = 0.15). Both in a landmark analysis and after adjustments for the established risk scores and selection of cases with biomarkers obtained, non-significant differences among the tertiles were observed. In the subpopulation no significant differences in clinical endpoints were observed among the tertiles. CONCLUSION: Lp-PLA2 activity levels at admission prior to pPCI in STEMI patients are not associated with the incidence of short and/or long-term clinical endpoints. Lp-PLA2 as an independent and clinically useful biomarker in the risk stratification of STEMI patients still remains to be proven.
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1-Alquil-2-acetilglicerofosfocolina Esterasa/sangre , Biomarcadores/sangre , Infarto del Miocardio/enzimología , Infarto del Miocardio/mortalidad , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio/cirugía , Admisión del Paciente , Intervención Coronaria Percutánea , Resultado del TratamientoRESUMEN
INTRODUCTION: Obesity and type 2 diabetes (T2D) are highly prevalent among African migrants compared with European descent populations. The underlying reasons still remain a puzzle. Gene-environmental interaction is now seen as a potential plausible factor contributing to the high prevalence of obesity and T2D, but has not yet been investigated. The overall aim of the Research on Obesity and Diabetes among African Migrants (RODAM) project is to understand the reasons for the high prevalence of obesity and T2D among sub-Saharan Africans in diaspora by (1) studying the complex interplay between environment (eg, lifestyle), healthcare, biochemical and (epi)genetic factors, and their relative contributions to the high prevalence of obesity and T2D; (2) to identify specific risk factors within these broad categories to guide intervention programmes and (3) to provide a basic knowledge for improving diagnosis and treatment. METHODS AND ANALYSIS: RODAM is a multicentre cross-sectional study among homogenous sub-Saharan African participants (ie, Ghanaians) aged >25 years living in rural and urban Ghana, the Netherlands, Germany and the UK (http://rod-am.eu/). Standardised data on the main outcomes, genetic and non-genetic factors are collected in all locations. The aim is to recruit 6250 individuals comprising five subgroups of 1250 individuals from each site. In Ghana, Kumasi and Obuasi (urban stratum) and villages in the Ashanti region (rural stratum) are served as recruitment sites. In Europe, Ghanaian migrants are selected through the municipality or Ghanaian organisations registers. ETHICS AND DISSEMINATION: Ethical approval has been obtained in all sites. This paper gives an overview of the rationale, conceptual framework and methods of the study. The differences across locations will allow us to gain insight into genetic and non-genetic factors contributing to the occurrence of obesity and T2D and will inform targeted intervention and prevention programmes, and provide the basis for improving diagnosis and treatment in these populations and beyond.
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Población Negra/estadística & datos numéricos , Diabetes Mellitus Tipo 2/etnología , Obesidad/etnología , Migrantes , Adulto , Estudios Transversales , Femenino , Alemania/epidemiología , Ghana/epidemiología , Humanos , Estilo de Vida , Masculino , Países Bajos/epidemiología , Prevalencia , Proyectos de Investigación , Factores de Riesgo , Estrés Psicológico , Reino Unido/epidemiologíaRESUMEN
OBJECTIVE: Pulmonary arterial hypertension due to congenital heart disease (CHD-PAH) has a poor prognosis. We sought to determine whether the biomarker high-sensitivity troponin T (hsTnT) measured on routine visit at the outpatient clinic is associated with prognosis. PATIENTS: Consecutive adult CHD-PAH (86% Eisenmenger syndrome) patients referred for advanced medical therapy between January 2005 and March 2007 in the Academic Medical Center in Amsterdam. Patients with severe renal impairment were excluded. MAIN OUTCOME MEASURE: The primary outcome was mortality. RESULTS: Of all 31 patients (mean age 45 ± 12 years) with CHD-PAH, eight patients died during a median follow-up of 5.6 (range 1.6 to 6.8) years. A hsTnT level >0.014 µg/L was the 99th percentile cutoff of the normal distribution and therefore defined as elevated. At baseline, elevated levels of hsTnT were found in eight patients (26%). In univariate Cox regression, hsTnT elevated at baseline, NT-pro-BNP and right ventricular function were determinants of death (P < .05 for all). Patients with elevated levels of hsTnT showed a significantly higher mortality rate as compared to patients with normal hsTnT levels (62% vs. 13%, P = .005). CONCLUSION: Levels of hsTnT were abnormal in a substantial proportion of CHD-PAH patients. A significant inverse relationship was found between hsTnT and survival.