A First Attempt into the Production of Acylglycerol Mixtures from Echium Oil.

Enzymatic glycerolysis of Echium oil (Echium plantagineum) has been carried out in the presence of four commercial lipases. Different pretreatments of the reaction mixture, such as high pressure homogenization and addition of food grade monoolein as an emulsifier, were evaluated to test their influence on the glycerolysis reaction. In addition, the impact of reducing temperature and the utilization of a solvent generally recognized as safe as a flavoring agent, such as limonene, were also investigated. Conversion of ca. 60-70% of triacylglycerols and production of ca. 25-30% of monoacylglycerols (MAGs) were attained. Finally, at the best reaction conditions, the glycerolysis reaction was scaled up at pilot plant and the product mixture obtained was fractionated via molecular distillation. From this stage, two products were attained: a distillate containing 80% of MAGs and a residue containing approximately 50% of diacylglycerols and 50% of triacylglycerols. All these mixtures can be utilized as self-emulsifying vehicles for the formulation of bioactive substances and also as precursors for the production of structured bioactive lipids.

Valor pronóstico a largo plazo de los valores séricos y urinarios del fragmento N-terminal del péptido natriurético tipo B y del filtrado glomerular en pacientes con insuficiencia cardíaca / Long-term prognosis of serum and urine n-terminal proBNP levels and glomerular filtration rate in heart failure patients

Fundamento y objetivo: El amino-terminal pro-brain natriuretic peptide (NT-proBNP, ‘fragmento N terminal del péptino natriurético tipo B’) y el filtrado glomerular renal (eFGR) están relacionados con el pronóstico a corto plazo en la insuficiencia cardíaca (IC). Este estudio evalúa el poder predictivo de los valores NT-proBNP séricos y urinarios, así como del eFGR en pacientes con IC en un seguimiento a 60 meses. Pacientes y método: Se estudiaron 93 pacientes diagnosticados de IC (66 varones, edad: 65±12 años). El episodio primario fue muerte cardiovascular y el episodio combinado fue mortalidad o ingreso de origen cardíaco. Resultados: Solamente los valores séricos de NT-proBNP tuvieron un área bajo la curva significativa para la presencia de mortalidad cardíaca y episodios combinados: 0,70 (p=0,004) y 0,67 (p=0,019), respectivamente. El NT-proBNP urinario y el eFGR no obtuvieron áreas bajo la curva significativas. Los pacientes con altos valores de NT-proBNP en suero tuvieron una peor supervivencia (44 [IC del 95%: 38–50] versus 56 [IC del 95%: 53–59] meses; p=0,0006) y pronóstico para episodios (33 [IC del 95%: 28–38] versus 42 [IC del 95%: 28–38] meses; p=0,027). Al englobar la concentración del péptido y la disfunción renal, los pacientes con NT-proBNP sérico alto y bajo eFGR tuvieron la peor supervivencia (42 [IC del 95%: 33–52] meses; p=0,010). Por último, sólo los valores de NT-proBNP séricos mayores de 933pg/ml y de 550pg/ml predicen muerte cardiovascular (hazard ratio=2,81; p=0,033) y episodios (hazard ratio=1,79; p=0,049), respectivamente. Conclusiones: Los valores de NT-proBNP séricos fueron un factor predictivo de mortalidad y episodios cardiovasculares a 60 meses, superior a los valores urinarios de NT-proBNP y eFGR, en pacientes diagnosticados de insuficiencia cardíaca con disfunción renal moderada (AU)

Background and objective: The amino-terminal pro-brain natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR) values are related to short prognosis in patients with heart failure (HF). This study evaluates the prognostic power of serum and urinary NT-proBNP levels, and eGFR values, in HF patients during a 60-month follow-up. Patients and Methods: We studied 93 HF outpatients (66 males, age 65±12). Primary endpoint was defined as cardiovascular mortality and secondary endpoint as cardiovascular mortality or admissions. Results: Only serum NT-proBNP levels had a significant area under the curve for the prognosis of 60-month mortality and combined events, 0.70 (p=0.004) and 0.67 (p=0.019), respectively. Urinary NT-proBNP and eGFR did not have statistical significant areas under the curve. Patients with high serum NT-proBNP had the highest risk of cardiovascular death [44 (IC 95% 38–50) vs. 56 (IC 95% 53–59) months, p=0.0006] and combined events [33 (IC 95% 28–38) vs. 42 (IC 95% 28–38) months; p=0.027]. After the integration of serum NT-proBNP and renal function, patients with high peptide levels and low eGFR had the worst survival [42 (IC 95% 33–52) months; p=0.010]. Finally, only serum NT-proBNP concentration above 933pg/mL was a predictor of poor survival (hazard ratio=2.81, p=0.033) and NT-proBNP above 550pg/mL for combined events (hazard ratio=1.79, p=0.049). Conclusions: Serum NT-proBNP levels were superior to urine NT-proBNP and eGFR values for predicting 60-month cardiovascular death and combined events in HF patients (AU)

[Long-term prognosis of serum and urine n-terminal proBNP levels and glomerular filtration rate in heart failure patients]. / Valor pronóstico a largo plazo de los valores séricos y urinarios del fragmento N-terminal del péptido natriurético tipo B y del filtrado glomerular en pacientes con insuficiencia cardíaca.

BACKGROUND AND OBJECTIVE: The amino-terminal pro-brain natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR) values are related to short prognosis in patients with heart failure (HF). This study evaluates the prognostic power of serum and urinary NT-proBNP levels, and eGFR values, in HF patients during a 60-month follow-up. PATIENTS AND METHODS: We studied 93 HF outpatients (66 males, age 65+/-12). Primary endpoint was defined as cardiovascular mortality and secondary endpoint as cardiovascular mortality or admissions. RESULTS: Only serum NT-proBNP levels had a significant area under the curve for the prognosis of 60-month mortality and combined events, 0.70 (p=0.004) and 0.67 (p=0.019), respectively. Urinary NT-proBNP and eGFR did not have statistical significant areas under the curve. Patients with high serum NT-proBNP had the highest risk of cardiovascular death [44 (IC 95% 38-50) vs. 56 (IC 95% 53-59) months, p=0.0006] and combined events [33 (IC 95% 28-38) vs. 42 (IC 95% 28-38) months; p=0.027]. After the integration of serum NT-proBNP and renal function, patients with high peptide levels and low eGFR had the worst survival [42 (IC 95% 33-52) months; p=0.010]. Finally, only serum NT-proBNP concentration above 933 pg/mL was a predictor of poor survival (hazard ratio=2.81, p=0.033) and NT-proBNP above 550 pg/mL for combined events (hazard ratio=1.79, p=0.049). CONCLUSIONS: Serum NT-proBNP levels were superior to urine NT-proBNP and eGFR values for predicting 60-month cardiovascular death and combined events in HF patients.

Effect of statin treatment on mortality in a large cohort of heart failure patients.

We studied 3162 heart failure patients included in the Spanish BADAPIC registry in order to determine whether statin treatment influences prognosis. Patients were followed up for 35 +/- 22 months (median, 32 months). Patients on statins were more often male and had higher prevalences of risk factors, ischemic heart disease and systolic dysfunction (P< .001) than those not on statins. After adjustment for age, risk factors, ischemic heart disease, renal failure, ejection fraction, anemia, heart rate and drug treatment, statin treatment was found to be a favorable independent predictor of survival: the hazard ratio for mortality was 0.73 (95% confidence interval, 0.45-0.88; P< .001). During follow-up, the 3-year survival rate was higher in patients treated with statins (75% vs. 68%; P< .001). In patients with heart failure, statin treatment appears to be independently associated with better survival.

Inflammatory activation and left ventricular mass in essential hypertension.

BACKGROUND: Inflammation is an independent risk factor for high blood pressure, and as a consequence inflammatory cytokines could be related with left ventricular hypertrophy (LVH). We sought to assess the association and predictive role of different cytokine levels with LVH in a group of patients with essential hypertension (HT). METHODS: We studied 251 asymptomatic hypertensive patients (142 with LVH and 109 without LVH), referred from 11 hospitals. A routine physical examination, laboratory analyses, and echo-Doppler study were performed. Plasma soluble tumor necrosis factor (TNF) receptors (sTNF-R1 and sTNF-R2), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1ra) were centrally determined. RESULTS: Hypertensive patients with LVH had higher inflammatory cytokine levels than the group without hypertrophy (P < 0.001). Multivariate linear regression reported that sTNF-R1 (P < 0.01) was an independent predictor of left ventricular mass index (LVMI). All cytokines had significant area under the curves for detection of LVH, but sTNF-R1 has the highest area, 0.71 +/- 0.03 (P < 0.001). Finally, prevalence of LVH was increased in the group of patients with higher cytokine levels, and logistic regression analysis showed that sTNF-R1 (odds ratio = 2.59, 95% CI of 1.14-5.87) was an independent predictor of LVH. CONCLUSIONS: Cytokine levels were significantly correlated with LVMI in hypertensive patients. The sTNF-R1 was an independent predictor of LVMI. Plasma sTNF-R1 concentrations could be a predictive factor of LVH in patients with essential HT.

[Interleukin-4 and cardiac fibrosis in patients with heart failure]. / Interleucina-4 y fibrosis miocárdica en pacientes con insuficiencia cardiaca.

Interleukin-4 (IL-4) stimulates inflammatory responses, activates collagen synthesis, promotes fibrosis progression, and inhibits the production of inflammatory cytokines. We studied the relationship between the urinary IL-4 level and levels of markers of cardiac fibrosis and left ventricular volume in 98 patients with heart failure (HF). The left ventricular end-systolic volume index (LVESVI) and left ventricular end-diastolic volume index (LVEDVI) were calculated, and IL-4, tumor necrosis factor-alpha (TNF-alpha), IL-6, and aminoterminal propeptide of procollagen type III (PIIINP) levels were recorded. Comparison of urinary IL-4 and PIIINP levels in patients and control subjects gave values of 12 (12) pg/mL and 4 (3) pg/mL (P<.0001), respectively, and 5 (2) ng/mL and 4 (1) ng/mL (P<.0001), respectively. The IL-4 level correlated with LVESVI and LVEDVI (r = -0.22, P<.05), and with PIIINP (r = 0.24, P<.05). In patients with hypertensive cardiomyopathy, there was a good correlation between IL-4 and PIIINP levels (r = 0.7, P<.01). Correlations were also observed between IL-4 and TNF-alpha (r = 0.3, P<.01) and IL-6 (r = 0.5, P<.0001). The urinary IL-4 level correlated with cardiac fibrosis and remodeling in patients with HF. The relationship was stronger in those with hypertensive cardiomyopathy.

Interleucina-4 y fibrosis miocárdica en pacientes con insuficiencia cardiaca / Interleukin-4 and cardiac fibrosis in patients with heart failure

La interleucina 4 (IL-4) estimula la respuesta inflamatoria, activa la síntesis de colágeno, promueve la progresión de fibrosis e inhibe la producción de citocinas inflamatorias. Estudiamos las concentraciones urinarias de IL-4, su relación con los marcadores de fibrosis miocárdica y con los volúmenes del ventrículo izquierdo en 98 pacientes con insuficiencia cardiaca. Calculamos el índice de volumen telesistólico (IVTS) y telediastólico (IVTD), los valores de IL-4, factor de necrosis tumoral (TNF) alfa , IL-6 y propéptido aminoterminal del procolágeno tipo III (PIIINP). Comparamos los valores urinarios de IL-4 y PIIINP en pacientes y controles (12 ± 12 frente a 4 ± 3 pg/ml, p < 0,0001 y 5 ± 2 frente a 4 ± 1 ng/ml, p < 0,0001). La IL-4 se correlacionó con IVTS e IVTD (r = ­0,22; p < 0,05) y con PIIINP (r = 0,24; p < 0,05). En la cardiopatía hipertensiva encontramos una correlación entre IL-4 y PIIINP (r = 0,7; p < 0,01). Correlacionamos la IL-4 con TNF-α y la IL-6, obteniendo r = 0,3, p < 0,01 y r = 0,5, p < 0,0001. La IL-4 en orina se relaciona con la fibrosis miocárdica y el remodelado en la insuficiencia cardiaca. La relación es mayor en la cardiopatía hipertensiva (AU)

Interleukin-4 (IL-4) stimulates inflammatory responses, activates collagen synthesis, promotes fibrosis progression, and inhibits the production of inflammatory cytokines. We studied the relationship between the urinary IL-4 level and levels of markers of cardiac fibrosis and left ventricular volume in 98 patients with heart failure (HF). The left ventricular end-systolic volume index (LVESVI) and left ventricular end-diastolic volume index (LVEDVI) were calculated, and IL-4, tumor necrosis factor-alpha (TNF-alpha), IL-6, and aminoterminal propeptide of procollagen type III (PIIINP) levels were recorded. Comparison of urinary IL-4 and PIIINP levels in patients and control subjects gave values of 12 (12) pg/mL and 4 (3) pg/mL (P<.0001), respectively, and 5 (2) ng/mL and 4 (1) ng/mL (P<.0001), respectively. The IL-4 level correlated with LVESVI and LVEDVI (r = ­0.22, P<.05), and with PIIINP (r = 0.24, P<.05). In patients with hypertensive cardiomyopathy, there was a good correlation between IL-4 and PIIINP levels (r = 0.7, P<.01). Correlations were also observed between IL-4 and TNF-alpha (r = 0.3, P<.01) and IL-6 (r = 0.5, P<.0001). The urinary IL-4 level correlated with cardiac fibrosis and remodeling in patients with HF. The relationship was stronger in those with hypertensive cardiomyopathy (AU)

[8-hydroxy-2'-deoxyguanosine and lipid peroxidation in patients with heart failure]. / Valores de 8-hidroxi-2'-desoxiguanosina y de peroxidación lipídica en pacientes con insuficiencia cardiaca.

INTRODUCTION AND OBJECTIVES: Heart failure is associated with increased free radical production, which leads to a state of oxidative stress. Known markers of oxidative stress include 8-hydroxy-2'-deoxyguanosine, which reflects oxidative damage to DNA, and lipid peroxidation, which can be used to quantify damage to lipid-rich structures. The aims of this study were to compare 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels in heart failure patients and healthy subjects and to assess how these levels are influenced by heart failure etiology. METHODS: The study included 78 patients (57 male, age 64 [14] years) with heart failure and 12 control subjects. Patients completed a questionnaire and were graded according to the New York Heart Association classification. Doppler echocardiography was performed and blood samples were obtained. 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels were determined. RESULTS: Significant differences were observed between patients and control subjects in 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels, at 0.34 (0.54) ng/mL vs 0.04 (0.07) ng/mL (P<.05), and 18 (10) microM vs 8 (3) microM (P<.01), respectively. Subsequent analysis showed that heart failure etiology had a significant effect on the levels of the two markers (P<.05), which were highest in patients with hypertensive cardiomyopathy. CONCLUSIONS: Levels of 8-hydroxy-2'-deoxyguanosine and lipid peroxidation were higher in heart failure patients than in control subjects. The most significant increases were found in patients with hypertensive cardiomyopathy.

Valores de 8-hidroxi-2'-desoxiguanosina y de peroxidación lipídica en pacientes con insuficiencia cardiaca / 8-Hydroxy-2'-deoxyguanosine and lipid peroxidation in patients with heart failure

Introducción y objetivos. La insuficiencia cardiaca está asociada con un incremento en la producción de radicales libres, llegándose al estado de estrés oxidativo. Se conocen diversos marcadores de estrés oxidativo, como la 8-hidroxi-2'-desoxiguanosina, marcador del daño oxidativo en el ADN, y la peroxidación lipídica que permite cuantificar el daño en las estructuras ricas en lípidos. El propósito de este estudio es comparar los valores de 8-hidroxi-2'-desoxiguanosina y de peroxidación lipídica en pacientes con insuficiencia cardiaca y sujetos sanos, y evaluar la influencia de la etiología. Métodos. Estudiamos a 78 pacientes (57 varones, edad 64 ± 14 años) diagnosticados de insuficiencia cardiaca y a 12 controles. Los pacientes completaron un cuestionario y fueron clasificados de acuerdo con la New York Heart Association. Se les realizó un estudio eco-Doppler y extracción de sangre. Medimos las concentraciones de 8-hidroxi-2'-desoxiguanosina y de peroxidación lipídica. Resultados. Al comparar los valores de 8-hidroxi-2'-desoxiguanosina y peroxidación lipídica entre pacientes y controles obtuvimos diferencias significativas (0,34 ± 0,54 frente a 0,04 ± 0,07 ng/ml, p < 0,05 y 18 ± 10 frente a 8 ± 3 μmol/l, p < 0,01, respectivamente). Cuando comparamos las concentraciones de los 2 marcadores según la etiología de la insuficiencia cardiaca encontramos diferencias significativas en ambos (p < 0,05), que fueron mayores en la miocardiopatía hipertensiva. Conclusiones. Los valores de 8-hidroxi-2'-desoxiguanosina y peroxidación lipídica se encuentran aumentados en los pacientes con insuficiencia cardiaca al compararlos con los controles. El incremento más importante lo encontramos en pacientes con miocardiopatía hipertensiva

Introduction and objectives. Heart failure is associated with increased free radical production, which leads to a state of oxidative stress. Known markers of oxidative stress include 8-hydroxy-2'-deoxyguanosine, which reflects oxidative damage to DNA, and lipid peroxidation, which can be used to quantify damage to lipid-rich structures. The aims of this study were to compare 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels in heart failure patients and healthy subjects and to assess how these levels are influenced by heart failure etiology. Methods. The study included 78 patients (57 male, age 64 [14] years) with heart failure and 12 control subjects. Patients completed a questionnaire and were graded according to the New York Heart Association classification. Doppler echocardiography was performed and blood samples were obtained. 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels were determined. Results. Significant differences were observed between patients and control subjects in 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels, at 0.34 (0.54) ng/mL vs 0.04 (0.07) ng/mL (P<.05), and 18 (10) μM vs 8 (3) μM (P<.01), respectively. Subsequent analysis showed that heart failure etiology had a significant effect on the levels of the two markers (P<.05), which were highest in patients with hypertensive cardiomyopathy. Conclusions. Levels of 8-hydroxy-2'-deoxyguanosine and lipid peroxidation were higher in heart failure patients than in control subjects. The most significant increases were found in patients with hypertensive cardiomyopathy

[Myocardial remodeling and immunologic activation in patients with heart failure]. / Remodelado miocárdico y activación inmunitaria en pacientes con insuficiencia cardiaca.

INTRODUCTION AND OBJECTIVES: Immune response-mediated regulation of myocardial collagen remains poorly understood. Our objective was to investigate the relationship between ventricular remodeling and immunologic activation in patients with heart failure (HF) by comparing dilated and ischemic cardiomyopathy. METHODS: We studied 94 patients with HF and dilated cardiomyopathy (n=46) or ischemic cardiomyopathy (n=48). We recorded left ventricular (LV) volumes, E/A ratio, and ejection fraction. Plasma concentrations of tumor necrosis factor alpha (TNFalpha), soluble TNFa receptor I (sTNF-RI), sTNF-RII, interleukin-6 (IL-6) and IL-10 were measured. The serum procollagen type-III amino-terminal propeptide (PIIINP) level was also obtained. RESULTS: Ventricular volumes were greater in the dilated cardiomyopathy than in the ischemic cardiomyopathy group (P< .05). However, sTNF-RI, sTNF-RII and PIIINP levels were higher in the ischemic group (P< .05). In this group, there were significant correlations between ventricular volumes and IL-10 and sTNF-RII levels. There was also a significant correlation between PIIINP and sTNF-RII levels (r=0.30; P< .05). In the dilated cardiomyopathy group, there was a significant correlation between ventricular volumes and IL-10 level, and between PIIINP level and IL-6 (r=0.32; P< .05) and sTNF-RII levels (r=0.32; P< .05). Multiple linear regression analysis, which included cytokine levels, age, sex and ventricular function, showed that the sTNF-RII level was an independent predictor of the PIIINP level (adjusted r(2)=0.16; P< .0001) and of ventricular volumes (LV end-systolic volume index, adjusted r(2)=0.034; P< .05; and LV end-diastolic volume index, adjusted r(2)=.048; P< .05) in both groups. CONCLUSIONS: In HF, there is an interaction between proinflammatory cytokines and the extracellular matrix. Immunologic implications vary according to disease etiology. The elevation in proinflammatory cytokine and PIIINP levels is greater in patients with ischemic cardiomyopathy. Multiple regression analysis showed that the sTNF-RII level was an independent predictor of ventricular remodeling.

Remodelado miocárdico y activación inmunitaria en pacientes con insuficiencia cardiaca / Myocardial remodeling and immunologic activation in patients with heart failure

Introducción y objetivos. No se comprende bien la regulación del colágeno miocárdico mediada por la respuesta inmunitaria. Nuestro objetivo fue determinar las relaciones entre remodelado ventricular y activación inmunitaria en pacientes con insuficiencia cardiaca comparando miocardiopatía isquémica y dilatada. Métodos. Estudiamos a 94 pacientes con insuficiencia cardiaca: miocardiopatía dilatada (n = 46) e isquémica (n = 48). Determinamos volúmenes ventriculares, E/A y FE. Medimos las concentraciones de TNFα, sTNF-RI, sTNF-RII, IL-6 e IL-10 y calculamos los valores de PIIINP. Resultados. Los volúmenes ventriculares en la miocardiopatía dilatada fueron superiores a los del grupo isquémico (p < 0,05). Sin embargo, los valores de sTNF-RI, sTNF-RII y PIIINP fueron más elevados en el grupo isquémico (p < 0,05). En éste, los volúmenes ventriculares se correlacionaron significativamente con IL-10 y sTNF-RII. El PIIINP se correlacionó significativamente con sTNF-RII (r = 0,30; p < 0,05). En el grupo de miocardiopatía dilatada, los volúmenes ventriculares se correlacionaron significativamente con IL-10 y el PIIINP se correlacionó con IL-6 (r = 0,32; p < 0,05) y sTNF-RII (r = 0,32; p < 0,05). La regresión lineal múltiple, que incluyó citocinas, edad, sexo y función ventricular, demuestra que el sTNF-RII es un factor pronóstico independiente del PIIINP (r² ajustada = 0,16; p < 0,0001) y de los volúmenes ventriculares (IVTSVI, r² ajustada = 0,034; p < 0,05; IVTDVI, r² ajustada = 0,048; p < 0,05) en ambos grupos. Conclusiones. En la insuficiencia cardiaca hay una interacción de citocinas proinflamatorias con la matriz extracelular. La implicación inmunitaria es diferente dependiendo de la etiología. Las citocinas proinflamatorias y los valores de PIIINP son más elevados en los pacientes con miocardiopatía isquémica. La regresión múltiple demostró que el sTNF-RII es un factor pronóstico independiente de remodelado ventricular (AU)

Introduction and objectives. Immune response-mediated regulation of myocardial collagen remains poorly understood. Our objective was to investigate the relationship between ventricular remodeling and immunologic activation in patients with heart failure (HF) by comparing dilated and ischemic cardiomyopathy. Methods. We studied 94 patients with HF and dilated cardiomyopathy (n=46) or ischemic cardiomyopathy (n=48). We recorded left ventricular (LV) volumes, E/A ratio, and ejection fraction. Plasma concentrations of tumor necrosis factor α (TNFα), soluble TNFa receptor I (sTNF-RI), sTNF-RII, interleukin-6 (IL-6) and IL-10 were measured. The serum procollagen type-III amino-terminal propeptide (PIIINP) level was also obtained. Results. Ventricular volumes were greater in the dilated cardiomyopathy than in the ischemic cardiomyopathy group (P<.05). However, sTNF-RI, sTNF-RII and PIIINP levels were higher in the ischemic group (P<.05). In this group, there were significant correlations between ventricular volumes and IL-10 and sTNF-RII levels. There was also a significant correlation between PIIINP and sTNF-RII levels (r=0.30; P<.05). In the dilated cardiomyopathy group, there was a significant correlation between ventricular volumes and IL-10 level, and between PIIINP level and IL-6 (r=0.32; P<.05) and sTNF-RII levels (r=0.32; P<.05). Multiple linear regression analysis, which included cytokine levels, age, sex and ventricular function, showed that the sTNF-RII level was an independent predictor of the PIIINP level (adjusted r²=0.16; P<.0001) and of ventricular volumes (LV end-systolic volume index, adjusted r²=0.034; P<.05; and LV end-diastolic volume index, adjusted r²=.048; P<.05) in both groups. Conclusions. In HF, there is an interaction between proinflammatory cytokines and the extracellular matrix. Immunologic implications vary according to disease etiology. The elevation in proinflammatory cytokine and PIIINP levels is greater in patients with ischemic cardiomyopathy. Multiple regression analysis showed that the sTNF-RII level was an independent predictor of ventricular remodeling (AU)

[Utility of NT-proBNP for diagnosing heart failure in a heterogeneous population of patients with dyspnea. Spanish multicenter study]. / Utilidad del NT-proBNP para el diagnóstico de insuficiencia cardiaca en una población heterogénea de pacientes con disnea. Estudio multicéntrico español.

INTRODUCTION AND OBJECTIVES: Recent studies have shown that brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are useful in the diagnosis of heart failure in patients presenting with dyspnea. However, the cutoff values used with these markers vary according to patient characteristics and dyspnea severity. The aim of this study was to investigate the diagnostic accuracy of using the plasma NT-proBNP level for identifying heart failure in a heterogeneous population of patients with dyspnea. METHODS: A multicentre study involving 247 consecutive patients with recent-onset dyspnea was carried out at 12 Spanish hospitals. Patients previously diagnosed with heart failure or any other condition known to cause dyspnea were excluded. RESULTS: Of the 247 patients, 161 (65%) had heart failure. The remaining 86 (35%) presented with dyspnea of non-cardiac origin. Plasma NT-proBNP levels were higher in patients with heart failure (5600 [7988] pg/mL vs 1182 [4406] pg/mL; P=.0001), and increased as functional status deteriorated (P=.036). The area under the receiver operating characteristic curve was 0.87 (0.02) (95% CI, 0.81-0.91) for the optimum cutoff value of 1335 pg/mL. The sensitivity of this cutoff value for diagnosing heart failure was 77% (95% CI, 70%-83%), the specificity was 92% (95% CI, 84%-97%), the positive predictive value was 94%, and the negative predictive value was 68%. CONCLUSIONS: The plasma NT-proBNP concentration provides an accurate means of diagnosing heart failure. However, the negative predictive value found in this study was somewhat lower than the values found in previous studies involving more homogeneous patient populations.

Utilidad del NT-proBNP para el diagnóstico de insuficiencia cardiaca en una población heterogénea de pacientes con disnea. Estudio multicéntrico español / Utility of NT-proBNP for diagnosing heart failure in a heterogeneous population of patients with dyspnea. Spanish multicenter study

Introducción y objetivos. En estudios recientes se ha demostrado la utilidad de los péptidos natriuréticos cerebrales (BNP) para el diagnóstico de insuficiencia cardiaca. Sin embargo, los valores de corte de estos marcadores difieren según las características de los pacientes y la severidad de la disnea. El objetivo de nuestro estudio fue evaluar la eficacia diagnóstica de los valores plasmáticos de la fracción N-terminal del BNP (NT-proBNP) en una población heterogénea de pacientes con disnea. Métodos. Realizamos un estudio multicéntrico en 12 hospitales españoles en el que se incluyó a 247 pacientes que consultaron de forma consecutiva por disnea de reciente comienzo. Se excluyó a los pacientes previamente diagnosticados de insuficiencia cardiaca u otras causas conocidas de disnea. Resultados. De los 247 pacientes, 161 (65%) fueron diagnosticados de insuficiencia cardiaca y 86 (35%) presentaron disnea de origen no cardiaco. Los valores plasmáticos de NT-proBNP fueron más elevados en los pacientes con insuficiencia cardiaca (5.600 ± 7.988 frente a 1.182 ± 4.406 pg/ml; p = 0,0001), y fueron mayores con peor clase funcional (p = 0,036). El área bajo la curva ROC fue 0,87 ± 0,02 (intervalo de confianza [IC] del 95%, 0,81-0,91), para un valor de corte óptimo de 1.335 pg/ml. La sensibilidad de este valor de corte para diagnosticar insuficiencia cardiaca fue del 77% (IC del 95%, 70-83%); la especificidad, del 92% (IC del 95%, 84-97%); el valor predictivo positivo, del 94%, y el valor predictivo negativo del 68%. Conclusiones. Las concentraciones plasmáticas de NT-proBNP son útiles para el diagnóstico de insuficiencia cardiaca en este tipo de pacientes, aunque el valor predictivo negativo es algo más bajo que en estudios previos que incluyeron a pacientes más homogéneos (AU)

Introduction and objectives. Recent studies have shown that brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are useful in the diagnosis of heart failure in patients presenting with dyspnea. However, the cutoff values used with these markers vary according to patient characteristics and dyspnea severity. The aim of this study was to investigate the diagnostic accuracy of using the plasma NT-proBNP level for identifying heart failure in a heterogeneous population of patients with dyspnea. Methods. A multicentre study involving 247 consecutive patients with recent-onset dyspnea was carried out at 12 Spanish hospitals. Patients previously diagnosed with heart failure or any other condition known to cause dyspnea were excluded. Results. Of the 247 patients, 161 (65%) had heart failure. The remaining 86 (35%) presented with dyspnea of non-cardiac origin. Plasma NT-proBNP levels were higher in patients with heart failure (5600 [7988] pg/mL vs 1182 [4406] pg/mL; P=.0001), and increased as functional status deteriorated (P=.036). The area under the receiver operating characteristic curve was 0.87 (0.02) (95% CI, 0.81-0.91) for the optimum cutoff value of 1335 pg/mL. The sensitivity of this cutoff value for diagnosing heart failure was 77% (95% CI, 70%-83%), the specificity was 92% (95% CI, 84%-97%), the positive predictive value was 94%, and the negative predictive value was 68%. Conclusions. The plasma NT-proBNP concentration provides an accurate means of diagnosing heart failure. However, the negative predictive value found in this study was somewhat lower than the values found in previous studies involving more homogeneous patient populations (AU)

Maximum longitudinal relaxation velocity of the left ventricle: its clinical value and relationship with NT-proBNP plasma levels in heart failure.

BACKGROUND: M-mode recordings of the mitral annulus to measure the maximum ascending velocity during early diastole as an expression of maximum longitudinal relaxation velocity of the left ventricle (RVm) can be used as an index of left ventricular (LV) diastolic function. The purpose of this study was to determine the relationship of RVm with LV functional parameters in patients with heart failure, with N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels, and with their functional classification. METHODS AND RESULTS: RVm was recorded in 97 patients by M-mode echocardiography. Patients were classified according to the New York Heart Association (NYHA) and the concentration of NT-proBNP was determined. Patients with ejection fraction (EF)>40 showed a significant correlation between RVm and mitral annulus motion (MAM), mitral flow propagation velocity, E/A, age, deceleration time (DT), and NT-proBNP. In patients with EF40, though its relationship with NT-proBNP both in patients with EF>or40 it is influenced only by age. RVm values showed a significant decrease in NYHA class II and III.

Diagnostic and prognostic value of urine NT-proBNP levels in heart failure patients.

BACKGROUND: Plasma NT-proBNP levels are sensitive markers of ventricular dysfunction. However, studies of natriuretic peptides in urine are limited. AIMS: To compare urine and plasma NT-proBNP levels and to investigate the diagnostic and prognostic value of urine levels in heart failure (HF). METHODS: Urinary and plasma NT-proBNP levels were measured in 96 HF patients and 20 control subjects. The patients were functionally classified according to the NYHA criteria. RESULTS: Urine NT-proBNP was higher in HF patients than in control subjects (94+/-31 pg/ml vs. 67+/-6 pg/ml, p<0.0001), correlating with plasma NT-proBNP levels (r=0.78, p<0.0001). Urinary levels were elevated in the more severe functional classes and diminished in obese patients. Urine NT-proBNP was a good tool for diagnosis of HF, the area under the curve (AUC) being 0.96+/-0.02 (p<0.0001), and for predicting 12-month cardiac events (p=0.011). To determine the prognostic power of urinary NT-proBNP in detecting 12-month cardiac mortality, we obtained an AUC of 0.75+/-0.10 (p=0.015). CONCLUSION: Urinary NT-proBNP, a relatively simple non-invasive test, is a new candidate marker for the diagnosis and evaluation of prognosis in HF and for the characterization of functional status in these patients.

[Plasma concentration of big endothelin-1 and its relation with plasma NT-proBNP and ventricular function in heart failure patients]. / Relación de los valores plasmáticos de big endotelina-1 con NT-proBNP y la función ventricular de pacientes con insuficiencia cardíaca.

INTRODUCTION AND OBJECTIVES: Elevated plasma concentrations of big endothelin-1 (big ET-1) are related with severity and prognosis in patients with heart failure, and N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of ventricular remodeling. The purpose of this study was to investigate the relationship between plasma levels of big ET-1 and NT-proBNP, and between the former and ventricular function. PATIENTS AND METHOD: We studied 103 patients with heart failure (75 men, mean age 63 [13] years). Each participant completed a questionnaire and underwent Doppler echocardiographic study to measure ejection fraction (EF), mitral flow propagation velocity (Vp) and atrioventricular plane displacement (AVPD). Blood samples were also taken to determine plasma levels of big ET-1, aldosterone and NT-proBNP. RESULTS: For the whole population big ET-1 concentration was 1.03 [0.75] fmol/m, NT-proBNP 619 (307-1328) pg/mL, aldosterone 168 [102] pg/mL, EF 37 [10], Vp 37 [11] cm/s, and AVPD 8.0 [1.7] mm. Plasma big ET-1 correlated positively with plasma NT-proBNP (r=0.50, P<.0001). However, a negative correlation was found between big ET-1 and EF (r=-0.30, P<.01), Vp, (r=-0.30, P<.01) and AVPD (r=-0.21, P<.05). When ET-1 levels were divided into quartiles and the corresponding NT-proBNP, EF, Vp and AVPD values were compared, we found significant differences (ANOVA P<.0001, P<.01, P<.05 and P<.05, respectively). CONCLUSIONS: Plasma levels of big ET-1 correlated positively with NT-proBNP levels and inversely with EF, Vp and AVPD. These findings help clarify the relationships between ventricular function and the neurohormonal activation involved in heart failure, and may aid the search for therapeutic interventions.

Relación de los valores plasmáticos de big endotelina-1 con NT-proBNP y la función ventricular de pacientes con insuficiencia cardíaca / Plasma concentration of big endothelin-1 and its relation with plasma NT-proBNP and ventricular function in heart failure patients

Introducción y objetivos. Las concentraciones elevadas de big endotelina 1 (big ET-1) se relacionan con la gravedad y el pronóstico de los pacientes con insuficiencia cardíaca (IC), mientras que N-terminal proBNP (NTproBNP) es un marcador de remodelado ventricular. El objetivo de nuestro estudio fue relacionar los valores debig ET-1 con NT-proBNP y con la función miocárdica. Pacientes y método. Estudiamos a 103 pacientes (75varones; 63 ± 13 años) diagnosticados de IC. Cada participante completó un cuestionario y fue sometido a un estudio eco-Doppler para la medición de la fracción de eyección (FE), la velocidad de propagación del flujo mitral (Vp) y el desplazamiento del plano auriculo ventricular(DPAV). Se realizó una extracción de sangre para determinarlos valores de big ET-1, aldosterona y NT-proBNP. Resultados. Para toda la población, el valor de big ET-1 fue de 1,03 ± 0,75 fmol/ml, el de NT-proBNP de 619(307-1.328) pg/ml, el de aldosterona de 168 ± 102 pg/ml,la FE de 37 ± 10, la Vp de 37 ± 11 cm/s y el DPAV de 8,0± 1,7 mm. La big ET-1 se correlacionó positivamente con el NT-proBNP (r = 0,50; p < 0,0001) e inversamente conla FE (r = -0,30; p < 0,01), la Vp (r = -0,30; p < 0,01) y elDPAV (r = -0,21; p < 0,05). Al dividir la big ET-1 en cuartiles y comparar los valores de NT-proBNP, FE, Vp y DPAV obtuvimos diferencias estadísticamente significativas(ANOVA p < 0,0001, p < 0,01, p < 0,05 y p < 0,05,respectivamente). Conclusiones. Los valores plasmáticos de big ET-1muestran una correlación positiva con los de NT-pro BNP y una correlación inversa con la FE, la Vp y el DPAV. Estos hallazgos ayudan a esclarecer las relaciones entre la función ventricular y la activación neurohormonal en la insuficiencia cardíaca y facilitan la búsqueda de nuevas intervención es terapéuticas

Introduction and objectives. Elevated plasma concentrations of big endothelin-1 (big ET-1) are related with severity and prognosis in patients with heart failure, and N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of ventricular remodeling. The purpose of this study was to investigate the relationship between plasma levels of bigET-1 and NT-proBNP, and between the former and ventricular function. Patients and method. We studied 103 patients with heart failure (75 men, mean age 63 [13] years). Each participant completed a questionnaire and underwent Doppler echocardiographic study to measure ejection fraction(EF), mitral flow propagation velocity (Vp) and atrioventricular plane displacement (AVPD). Blood samples were also taken to determine plasma levels of big ET-1, aldosterone and NT-proBNP. Results. For the whole population big ET-1 concentration was 1.03 [0.75] fmol/m, NT-proBNP 619 (307-1328)pg/mL, aldosterone 168 [102] pg/mL, EF 37 [10], Vp 37[11] cm/s, and AVPD 8.0 [1.7] mm. Plasma big ET-1 correlated positively with plasma NT-proBNP (r=0.50,P<.0001). However, a negative correlation was found between big ET-1 and EF (r=-0.30, P<.01), Vp, (r=-0.30,P<.01) and AVPD (r=-0.21, P<.05). When ET-1 levels were divided into quartiles and the corresponding NT proBNP, EF, Vp and AVPD values were compared, we found significant differences (ANOVA P<.0001, P<.01,P<.05 and P<.05, respectively). Conclusions. Plasma levels of big ET-1 correlated positively with NT-proBNP levels and inversely with EF, Vpand AVPD. These findings help clarify the relationships between ventricular function and the neurohormonal activation involved in heart failure, and may aid the search for therapeutic interventions

Ventricular hypertrophy increases NT-proBNP in subjects with and without hypertension.

BACKGROUND: It has been published that hypertension (HT) must be taken into account when using NT-proBNP, but left ventricular (LV) hypertrophy without HT could be a cause of NT-proBNP elevation. In a population study we compared NT-proBNP in subjects with hypertrophy, with and without diagnosis of HT. METHODS: We studied 215 subjects from a random sample of 432 people who had declared to suffer from dyspnea. These 432 subjects were referred to their hospital where blood samples were taken, an echo-Doppler study was performed and a specific questionnaire was completed. We got a positive answer from 215, and 52 (24%) have LV hypertrophy. RESULTS: When we compared NT-proBNP in non-hypertrophic population, 148 +/- 286 pg/ml, with NT-proBNP in LV hypertrophic population, 202 +/- 209 pg/ml, we found P < 0.001. In the hypertrophic group, when we compared NT-proBNP (199 +/- 201 pg/ml) in normotensive subjects (LV mass index 170 +/- 70 g/m2, Vp 50 +/- 18 cm/s, LVEF 62 +/- 8) with NT-proBNP (205 +/- 220 pg/ml) in subjects with diagnosis of HT (LV mass index 169 +/- 37 g/m2, Vp 55 +/- 20 cm/s, LVEF 64 +/- 10), we found NS. CONCLUSIONS: This population study shows that NT-proBNP is elevated in patients with LV hypertrophy with or without HT. In LV hypertrophy the presence of HT does not influence the peptide levels significantly.

[NT-proBNP levels and hypertension. Their importance in the diagnosis of heart failure]. / Hipertensión y valores de NT-proBNP. Su importancia en el diagnóstico de insuficiencia cardíaca.

INTRODUCTION: N-terminal pro-brain natriuretic peptide (NT-proBNP) is useful in the diagnosis of heart failure. We compared NT-proBNP levels in patients with and without a diagnosis of arterial hypertension. PATIENTS AND METHOD: Participants were recruited from a random sample of 999 inhabitants from the Community of Valencia (eastern Spain). Of these patients, 432 said they suffered from dyspnea and were referred to their hospital (10 hospitals involved), where blood samples were taken, an echo-Doppler study was performed, and the patients completed a questionnaire. Of the 432 participants with dyspnea, 215 gave informed consent for their inclusion in the study, and 202 completed the study. Hypertension was diagnosed in 72 participants and 130 were normotensive. RESULTS: For the whole population, NT-proBNP, expressed as the median and range, was 88 (0-2586) pg/mL. When we compared hypertensive with normotensive participants, we found higher NT-proBNP levels in the former group: median 123, range 0-2184 pg/mL, versus median 77, range 0-2586 pg/mL (P<.01). When we excluded subjects with systolic left ventricular dysfunction, we found higher levels in participants with hypertension: 119 (0-2184 pg/mL) vs 72 (0-997 pg/mL) (P<.01). When we also excluded subjects with diastolic dysfunction, we found (median 85, range 0-430 pg/mL) and (median 66, range 0-997 pg/mL), respectively (p = NS). CONCLUSION: In a population study of subjects with dyspnea, hypertensive patients have higher NT-proBNP levels than subjects with normal blood pressure. This difference disappeared when patients with diastolic dysfunction were excluded from the analysis. Hypertension can thus be a confounding factor that potentially decreases the specificity of NT-proBNP levels for the diagnosis of heart failure. These findings should be taken into account when conducting clinical and epidemiological studies in which patients with both heart failure and hypertension are included.