Improved diagnostic and prognostic performance of a new high-sensitive troponin T assay in patients with acute coronary syndrome.

BACKGROUND: In the present study, we aimed to analyze the diagnostic and prognostic potential of a newly developed high-sensitive troponin T assay and compared these results with those of a contemporary troponin T assay in 2 distinct patient cohorts, one including patients with evident ACS and the other one including patients with general chest pain. METHODS AND RESULTS: For this study, we analyzed data from 2 independent patient cohorts, the Bad Nauheim ACS registry and the Prognosis in Acute Coronary Syndromes registry, with a total of 2,506 patients. On admission, clinical data have been recorded, and a single measurement of troponin T has been performed with a contemporary assay (TnT) and a new high-sensitive troponin T assay (hsTnT). Clinical follow-up has been obtained after 6 months. The diagnostic value of hsTnT was superior to TnT (area under the receiver operating characteristic curve 0.949 vs 0.929, P = .016). Specifically, in TnT-negative patients, hsTnT provided strong diagnostic information (area under the receiver operating characteristic curve of 0.81, P < .001). Furthermore, hsTnT provided independent prognostic power for mortality within 6 months in both cohorts, which was superior to that of the contemporary TnT assay. CONCLUSION: Troponin T measured with a newly developed hsTnT provides better diagnostic and prognostic information and, therefore, should be implemented as a standard test in clinical routine.

Distribution and prognostic value of high-sensitive troponin T measurement in patients with type 2 diabetes without cardiovascular disease.

AIM: The objective of this work was to define a value for the 99th percentile of high-sensitive troponin T and to evaluate the prognostic value of this biomarker in a population of patients with type 2 diabetes without a history of cardiovascular disease. METHODS: In this prospective, observational and analytic study, 482 patients with type 2 diabetes were enrolled. The patients were asymptomatic, with no history of cardiovascular events, renal insufficiency, or inflammatory or systemic disease. As events we considered a combined end point of major adverse cardiovascular events (MACE). RESULTS: 94.9% of the patients had detectable troponin values, 20.7% of the patients had troponin values above the healthy population reference upper threshold (14pg/mL). The 99th percentile value for this patient population was 48pg/mL. Age, sex, the glomerular filtration rate and hypertension were associated with troponin values>14pg/mL. The incidence of MACE was 3.96 per 100 patients/year (p/y) between those with hs-TnT>14pg/mL and 1.07 per 100 p/y between those with hs-TnT≤14pg/mL (HR=3.78 CI95 1.49-9.58; p=0.005). CONCLUSIONS: The 99th percentile value of troponin T in a population of patients with type 2 diabetes is 3-fold higher than the value proposed by the manufacturer for a healthy population. We also observed a significant difference in the distribution of troponin T values between men and women. This biomarker may be a valuable prognostic factor, since troponin T values above the reference upper threshold were associated with an increase in the risk of cardiovascular events in these patients.

Distribution and prognostic value of high-sensitive troponin T measurement in patients with type 2 diabetes without cardiovascular disease.

AIM: The objective of this work was to define a value for the 99th percentile of high-sensitive troponin T and to evaluate the prognostic value of this biomarker in a population of patients with type 2 diabetes without a history of cardiovascular disease. METHODS: In this prospective, observational and analytic study, 482 patients with type 2 diabetes were enrolled. The patients were asymptomatic, with no history of cardiovascular events, renal insufficiency, or inflammatory or systemic disease. As events we considered a combined end point of major adverse cardiovascular events (MACE). RESULTS: 94.9% of the patients had detectable troponin values, 20.7% of the patients had troponin values above the healthy population reference upper threshold (14pg/mL). The 99th percentile value for this patient population was 48pg/mL. Age, sex, the glomerular filtration rate and hypertension were associated with troponin values>14pg/mL. The incidence of MACE was 3.96 per 100 patients/year (p/y) between those with hs-TnT>14pg/mL and 1.07 per 100 p/y between those with hs-TnT≤14pg/mL (HR=3.78 CI95 1.49-9.58; p=0.005). CONCLUSIONS: The 99th percentile value of troponin T in a population of patients with type 2 diabetes is 3-fold higher than the value proposed by the manufacturer for a healthy population. We also observed a significant difference in the distribution of troponin T values between men and women. This biomarker may be a valuable prognostic factor, since troponin T values above the reference upper threshold were associated with an increase in the risk of cardiovascular events in these patients.

NT-probrain natriuretic peptide predicts complexity and severity of the coronary lesions in patients with non-ST-elevation acute coronary syndromes.

UNLABELLED: NT-probrain natriuretic peptide (NT-proBNP) has been associated with left ventricular (LV) dysfunction and adverse outcome in patients with non-ST-elevation acute coronary syndromes (NSTEACS). However, the underlying pathophysiological mechanisms responsible for this association have not been well established. We sought to explore the relation between NT-proBNP levels and extension of coronary artery disease (CAD) and the presence of more complex and severe coronary lesions. METHODS: This prospective, multicenter angiographic substudy included 585 patients admitted with NSTEACS. Blinded measurements of NT-proBNP and troponin T were performed at a median time of 3 hours after admission and analyzed centrally. Angiograms were read at a core laboratory by 2 independent readers blinded to patient data. Complex coronary lesion was defined as the presence of at least one of the following: thrombus (+), TIMI flow < 2, or ulcerated plaque. RESULTS: NT-probrain natriuretic peptide levels increased proportionally as LV function decreased. The levels of NT-proBNP were directly related to the extent of the CAD. This association was maintained when we analyzed patients with normal LV function (n = 257). Patients with complex coronary lesions or those with at least one of its individual component had higher levels of NT-proBNP compared with those without complex coronary lesions. After adjusting for clinical and electrocardiographic variables and other biomarkers, positive troponin (OR 2.20, 95% CI 1.50-3.22, P < .0001) and supramedian NT-proBNP levels (OR 1.72, 95% CI 1.19-2.47, P = .003) independently contributed to the prediction of complex coronary lesions. CONCLUSION: In this study of patients with NSTEACS, NT-proBNP levels progressively increase with the severity of CAD and degree of LV dysfunction. Increased levels of NT-proBNP independently predict the presence of more complex coronary lesions.

Transtubular potassium concentration gradient: comparison between healthy old people and chronic renal failure patients.

UNLABELLED: Transtubular potassium concentration gradient (TTKG) is an index of potassium secretory activity in the distal tubule. Since water reabsorption takes place in the distal tubule as well, urine potassium concentration is a less accurate index evaluating distal K+ secretion because the effect of water is not taken into account on urine potassium concentrations. Potassium secretion and water reabsorption are strongly related to age and renal function. As a consequence, TTKG would be altered in both elderly individuals, as well as in patients with chronic renal failure (CRF). The aim of this study was to assess and compare TTKG in these two groups. PATIENTS & METHODS: A total of 55 individuals were studied, 12 of them were patients with CRF and 43 healthy elderly subjects with normal renal function. Informed consent was obtained from all patients. Patients with diabetes mellitus, cardiac failure, cirrhosis, obstructive uropathy, hyperkalemia, hypokalemia, or taking any medication that could alter the potassium balance were excluded from the study. All subjects were on a diet containing 50 mmol of potassium intake daily (documented by a three-day dietary record). Plasma potassium, creatinine, urea, glucose and osmolality were measured in all as well. 24 h creatinine clearance (CrCl ) and TTKG were calculated. Statistical analysis was made using Student's t-test. RESULTS: TTKG was significantly lower in the elderly group (4.2+/-1.9 vs 6.2+/-1.8 , P 0.005)Both groups had a significantly lower TTKG when compared to healthy young people (8+/-2). Plasma and urine potassium levels, as well as plasma osmolality were similar in the two groups. Only urine osmolality was lower in the CRF group (382+/-141 vs. 514+/-180, P=0.01) CONCLUSION: Both old age and renal impairment lead to a reduced TTKG in comparison with young healthy people. Furthermore, TTKG is significantly lower in elderly healthy subjects compared to patients with CRF.

Relation of C-reactive protein to extent and complexity of coronary narrowing in patients with non-ST elevation acute coronary syndromes. A prospective cohort study.

BACKGROUND: Inflammatory markers have been associated with adverse clinical outcome in patients with acute coronary syndromes (ACS). In addition, angiographic plaque morphology and extension of coronary artery disease has been related to worse prognosis in this group of patients. The aim of the present study was to determine if the clinical prognostic value of C-reactive protein (CRP), an inflammatory marker, can by associated with the angiographic findings in patients with non-ST elevation ACS. METHODS: This prospective multicenter cohort study included 1253 patients with non-ST elevation ACS. CRP, which was considered positive (+) if >/=3 mg/l, was measured at a median of 9 h from symptoms onset and were kept blinded until the end of the study. Coronary angiography was performed in 633 patients (50%). The presence of complex coronary lesions (CCLs) was defined as the presence of any of the following: thrombus (+), Thrombolysis In Myocardial Infarction (TIMI) flow

Furosemide test in stage III-chronic kidney disease and kidney transplant patients on tacrolimus.

AIM: Furosemide test is a simple and useful test of renal physiology usually used for evaluating the capability of the collecting ducts to secrete potassium under the effect of this drug. Its behaviour pattern has already been established in healthy children, young, and old people, as well as in stage III-chronic kidney disease (III-CKD) patients. However, its behaviour has not been described in kidney transplant patients yet, which we explored in this study. MATERIALS AND METHODS: Twenty young volunteers on a standard western diet (50 mmol of potassium/day) were studied: Ten were III-CKD and the rest were kidney transplant (KT) patients on FK. Before, while the test was being carried out, and 180 min after a single dose of intravenous furosemide (1 mg/kg), urine and blood samples were obtained, for creatinine and potassium levels. From these data, we calculated fractional excretion of potassium (FEK). Statistical analysis was performed applying Wilcoxon test. RESULTS: There was a significant difference regarding pre-furosemide (basal) FE of potassium between the III-CKD and KT groups 16 ± 5 (III-CKD) versus 7 ± 5 (KT), p = 0.008. Regarding the post-furosemide, peak FEK was significantly lower in the KT group (15 ± 11 %) compared to the III-CKD ones (49.8 ± 9 %, p = 0.01). In both groups, the peak FEK post-furosemide was reached later (120 min) compared to the conventional test (30 min). CONCLUSION: Furosemide test showed significantly lower basal and post-furosemide peak FEK values in KT patients on tacrolimus compared with stage III-chronic renal disease.

Fractional excretion of K, Na and Cl following furosemide infusion in healthy, young and very old people.

UNLABELLED: Furosemide test is a simple and useful test of renal physiology used to evaluate the capability of the collecting ducts to secrete potassium under the effect of serum aldosterone. Its behaviour pattern has been established in children and young adults but not described in very old healthy people, which we explored in this study. MATERIAL AND METHODS: Twenty-six healthy volunteers on a standard Western diet (50 mmol of K/day) were studied: 20 of them were young (between 17 and 40 years old) and the rest were very old (between 75 and 85 years old). They suffered from no diseases and were not on any medication. Before, during the test and 180 min after a single dose of intravenous furosemide (1 mg/kg), urine and blood samples were obtained for creatinine and electrolytes levels. From these data we calculated fractional excretion (FE) of electrolytes; serum aldosterone was measured pre and post furosemide infusion. Statistical analysis was performed by applying Student's t-test. RESULTS: There was no significant difference regarding pre-furosemide (basal) FE of potassium between the very old and young group. Post-furosemide average FE of potassium was significantly lower in the very old group (27.4 +/- 2%) compared with the young group (35.4 +/- 9%) (P = 0.04). Even though there was no significant difference in post-furosemide peak FE of potassium value, it was reached later in the very old (120 min) compared with the young (30 min). Serum aldosterone levels were significantly higher post furosemide in both groups: 18.3 +/- 12.2 ng/dl (pre) versus 32.5 +/- 18.6 ng/dl (post) in the young (P = 0.007) and 69.8 +/- 13.7 ng/dl (pre) versus 113.3 +/- 54.8 ng/dl (post) in the very old (P = 0.04). Furthermore, all serum aldosterone values (pre and post furosemide) were significantly higher in very old people compared with young people (P < 0.001). Basal fractional excretion of sodium and chloride were slightly higher in the very old group compared with the young group (P = 0.05). Average post-furosemide FE of sodium and chloride were slightly and significantly lower in the very old (P = 0.05 and P = 0.03), respectively. However, there was no significant difference in peak post-furosemide FE of sodium and chloride values, which were reached later in the very old (120 min) compared with the young (30 min). CONCLUSION: Furosemide test showed a significantly lower average post-furosemide FE of potassium value, delayed post-furosemide peak FE of Na, K and Cl and a hormonal pattern of aldosterone resistance in very old people.

Renal physiology in elderly persons with severe immobility syndrome.

OBJECTIVE: The immobility syndrome (IS) is a common condition in the elderly and consists of a reduction in the capacity to perform daily activities because of motor function deterioration. This syndrome leads to characteristic structural and physiological changes in the body, but renal physiology studies have not been conducted on this population. For this reason, we decided to study prospectively changes in renal function in these individuals. MATERIAL AND METHODS: We enrolled into this study 17 volunteers over 64 years of age, all of whom lived in the same nursing home. The patients were divided into two groups: nine healthy mobile persons and eight others who suffered from severe IS. Exclusion criteria were the presence of any disease or use of any drug that could induce water and electrolytes alteration. Blood and urine samples were drawn to measure sodium, potassium, creatinine, urea, calcium, phosphorus, magnesium, and uric acid in order to obtain their fractional excretion. Plasma osmolality and vasopressin were also measured. Total body water and lean body mass were obtained by bioelectrical impedance analysis. Statistical analysis was performed applying Student's t-test (P = 0.01) and Pearson's correlation test. RESULTS: A significant difference in body water composition was found between the groups. Thus in the IS group plasma sodium level was slightly lower and total water content was significantly higher than in the mobile subjects: 140 +/- 5 vs. 143 +/- 1 mmol/l (P = 0.01); 61 +/- 8% vs. 50 +/- 10% (P < 0.001), respectively. Despite these differences, plasma osmolality and vasopressin values were within the normal range in both groups. However, there was a good positive correlation between these two variables in the mobile group only: R 0.9 (mobile) vs. R -0.2 (immobile). We found no significant difference in plasma creatinine or fractional excretion of sodium, potassium, calcium, phosphorus, magnesium, urea, and uric acid between the groups. CONCLUSION: Total body water content was significantly higher in the elderly who suffered from severe immobility syndrome than in healthy mobile elderly. In contrast with the mobile group, for which there was a good positive correlation between plasma osmolality and plasma vasopressin, for individuals with IS there was no correlation between plasma osmolality and plasma vasopressin.

Correlation between creatinine clearance and transtubular potassium concentration gradient in old people and chronic renal disease patients.

Senescence and chronic kidney disease (CKD) reduce progressively glomerular filtration rate (GFR), which usually results in an increase in potassium renal secretion. To evaluate whether the transtubular potassium concentration gradient (TTKG) is more accurate parameter for evaluating the renal secretion of this cation than using fractional excretion of potassium as its urinary secretion marker, we studied 55 subjects, 43 of them were healthy elderly volunteers and 12 were CKD patients. Exclusion criteria were: abnormal plasma potassium level or presence of any disease or drug that could induce alteration of balance of this electrolyte levels. All the subjects were on a diet with a potassium content around 50 mmol/day. The curves, which demonstrate the relationship between creatinine clearance and TTKG and the grade of correlation between these two parameters were analyzed in both groups. We found that the transtubular potassium concentration gradient had a significant negative correlation with the creatinine clearance level in the healthy elderly group, while there was no correlation in the CKD group.

El NT-proBNP predice mal pronóstico en pacientes con síndromes coronarios agudos sin elevación del segmento ST y función ventricular conservada / NT-proBNP predicts clinical outcomes in patients with NSTE-ACS and preserved left ventricular function

Antecedentes: El NT-proBNP se asocia con disfunción ventricular y mala evolución en síndromes coronarios agudos sin elevación del ST (SCA-SEST). La evidencia sobre su valor pronóstico en pacientes con SCA-SEST y función sistólica conservada es escasa. Objetivos: Explorar el valor pronóstico del NT-proBNP en pacientes con SCA-SEST sin disfunción ventricular. Material y métodos: De una cohorte de pacientes con SCA-SEST sometidos a angiografía se seleccionaron 393 con fracción de eyección del ventrículo izquierdo menor igual 40 por ciento. Laboratorios centrales independientes analizaron las angiografías y las determinaciones de NT-proBNP, troponina T, mioglobina y proteína C reactiva. Se empleó un punto de corte de NT-proBNP de 586 pg/ml. El punto final primario fue la incidencia de muerte o infarto a los 180 días. Resultados: Ochenta y tres pacientes (21 por ciento) tuvieron NT-proBNP mayor igual 586 pg/ml y 310 (79 por ciento) niveles < 586 pg/ml. Los pacientes con NT-proBNP elevado eran más añosos, con mayor frecuencia de sexo femenino; tuvieron una proporción mayor de marcadores séricos elevados y una proporción mayor de enfermedad coronaria extensa y de lesiones coronarias complejas. Estos pacientes, comparados con aquellos con NT-proBNP < 586 pg/ml, tuvieron una incidencia mayor de muerte (9,6 por ciento versus 2,3 por ciento; p = 0,002), infarto (9,6 por ciento versus 3,2 por ciento; p = 0,01) y muerte o infarto (16,9 por ciento versus 5,5 por ciento; p = 0,001) a los 180 días. Ajustando por variables clínicas, electrocardiográficas y angiográficas, el NT-proBNP resultó ser un predictor independiente del punto final combinado de muerte o infarto a los 6 meses y de muerte por cualquier causa. Conclusiones: El NT-proBNP es un predictor independiente de muerte e infarto y de muerte global a los 6 meses en pacientes con SCA-SEST sin disfunción ventricular.

Determinación combinada de proteína C reactiva y troponina I en pacientes que concurren a la Unidad de Emergencias con dolor precordial / Prognostic value of C-reactive and troponin I C in patients with chest pain

Introducción y objetivos: Los hallazgos clínicos, electrocardiográficos y los niveles séricos de CK-MB son variables pronósticas en la evaluación de pacientes con dolor precordial. El objetivo de este trabajo fue determinar el valor pronóstico adicional de la troponina I (TnI) y de la proteína C reactiva (PCR) en una población de pacientes con dolor de precordial que consultan al Departamento de Emergencias. Material y métodos: Se realizó el seguimiento de 784 pacientes consecutivos con dolor precordial durante 120 días para evaluar la frecuencia de muerte o IM no fatal. Se obtuvo sangre al ingreso para evaluar los niveles de TnI y PCR. Los investigadores fueron ciegos a estos resultados. Resultados: Del total de pacientes, 394 (50,2 por ciento) fueron dados de alta (dolor no coronario) y 390 (49,8 por ciento) fueron hospitalizados con diagnóstico de angina inestable o infarto. La frecuencia de muerte o infarto a los 120 días fue del 3,8 por ciento; la frecuencia más alta (14,9 por ciento) se observó en el grupo con TnI y PCR elevadas (p = 0,0001). Se identificaron cuatro predictores independientes de muerte o infarto por regresión de Cox: enfermedad coronaria previa (HR 2,97, IC 95 por ciento 1,42- 6,25; p = 0,004); cambios del segmento ST (HR 3,01, IC 95 por ciento 1,31-7,14; p = 0,009); TnI = 0,4 ng/ml (HR 2,85, IC 95 por ciento 1,23-6,66; p = 0,015) y PCR = 5 mg/L (HR 2,42, IC 95 por ciento 1,45-5,26; p = 0,020). La combinación de TnI y PCR fue superior que la estratificación convencional por clínica y ECG, especialmente en el grupo de riesgo intermedio. Conclusiones: En pacientes con dolor torácico, la combinación de TnI y PCR mejora la estratificación de riesgo en comparación con el uso convencional de la clínica y el ECG, especialmente en los pacientes con un nivel de riesgo intermedio.

La proteína C reactiva no predice hallazgos coronarios de alto riesgo en los síndromes coronarios agudos sin elevación del ST: un estudio de cohorte prospectivo. Subestudio angiográfico del Estudio PACS / C-reactive protein don't predict high risk coronary angiographic findings in patients with non-st elevation acute coronary syndromes a large prospective cohort study

Antecedentes: Los marcadores inflamatorios se han asociado con una evolución clínica adversa en pacientes con síndromes coronarios agudos (SCA). Además, la morfología de la placa en la angiografía se relacionó con mal pronóstico, observándose una relación estrecha entre los marcadores de injuria miocárdica, como es la troponina T, y la presencia de lesiones coronarias complejas (LCC). Habiéndose postulado la teoría inflamatoria como un factor importante en el proceso fisiopatológico del SCA, el papel de los marcadores de inflamación para predecir aspectos angiográficos no se ha establecido. El propósito de este estudio fue el de determinar si la próteína C reactiva (PCR), un marcador inflamatorio, puede predecir la presencia de LCC. Material y métodos: Este estudio de cohorte prospectivo, multicéntrico incluyó 1252 pacientes con SCA sin elevación del ST. La PCR se midió en una mediana de 9 horas desde el comienzo de los síntomas, resultados que se mantuvieron ciegos hasta la finalización del estudio. De los pacientes en quienes se realizó angiografía coronaria, ingresaron en el estudio 590 (47 por ciento) y fueron revisadas por dos angiografistas que desconocían los resultados del laboratorio así como la evolución clínica. Se definieron LCC cuando existían algunas de la siguientes carecterísticas: trombo (+), flujo TIMI menor igual 2 o placa ulcerada (PU). Resultados: Se observó PCR (+) en 354 pacientes y PCR (-) en 236, 105 pacientes tuvieron trombos, de ellos 64 (18 por ciento) con PCR (+), 135 tuvieron flujo TIMI menor igual 2 y 81 (23 por ciento) con PCR (+). Finalmente 144 pacientes tuvieron lesiones ulceradas con un 30 por ciento (90 pacientes) con PCR (+). En total, 266 pacientes presentaron LCC, y de ellos el 47 por ciento (166 pacientes) con PCR (+) y 42 por ciento (100) p= 0,31. Conclusiones: En esta cohorte consecutiva de pacientes con SCA sin elevación del segmento ST, la proteína C reactiva, un marcador inflamatorio, no predijo la presencia de ninguno de los componentes de lesión coronaria compleja. A pesar de que la PCR es un fuerte predictor de mala evolución clínica, esto no se atribuiría a la presencia de una anatomía coronaria más compleja.