Galectina-3: experiencia en pacientes chilenos con diagnóstico de insuficiencia cardíaca descompensada / Galectin-3 levels in patients hospitalized for decompensated heart failure

Background: Galectin-3 (Gal-3) is a mediator of myocardial fibrosis involved in cardiac remodeling and a potential new prognosis marker in heart failure (HF). Aim: To measure Gal-3 at the moment of discharge in patients hospitalized for HF and its association with different variables. Material and Methods: Patients hospitalized for decompensated HF from four hospitals between August 2014 and March 2015, were included. Demographic, clinical and laboratory variables were recorded at the time of admission. At discharge, a blood sample was withdrawn to measure Gal-3 and brain natriuretic propeptide (Pro-BNP). Patients were separated in two groups, according to the level of Gal-3 (using a cutoff value of 17.8 ng/mL), comparing clinical and laboratory values between groups. Results: We included 52 patients with HF aged 70 ± 17 years (42% females). Functional capacity was III-IV in 46% of patients and the ejection fraction was 34.9 ± 13.4%. Pro-BNP values at discharge were 5,323 ± 8,665 pg/mL. Gal-3 values were 23.8 ± 16.6 ng/mL. Sixty percent of patients had values over 17.8 ng/mL. Those with elevated Gal-3 levels were older (75 ±16 and 62 ± 15 years, respectively, p = 0.025) and were hypertensive in a higher proportion (90.5% and 57.1% respectively, p = 0.021). Conclusions: In patients hospitalized for HF, Gal-3 levels are higher in older and hypertensive subjects.

Incidencia e importancia pronóstica del deterioro de la función renal en pacientes hospitalizados con insuficiencia cardiaca / Deterioration of kidney function as a risk factor for mortality among patients hospitalized for heart failure

Background: Acute deterioration of kidney function among patients admitted to the hospital for cardiac failure is associated with an increased mortality. Aim: To investigate the association between deterioration of kidney function and mortality among patients hospitalized for cardiac failure. Material and Methods: Patients admitted for decompensated cardiac failure to 14 Chilean hospitals between 2002 and 2009 were incorporated to the study. Clinical and laboratory features were registered. Serum creatinine values on admission and discharge were determined. Hospital and long term mortality was determined requesting death certificates to the National Identification Service at the end of follow up, lasting 635 ± 581 days. Results: One thousand sixty four patients were incorporated and 1100, aged 68 ± 13 years (45% females) had information about renal function. Seventy seven percent were hypertensive and 36% were diabetic. Mean ejection fraction was 41 ± 18% and 34% had an ejection fraction over 50%. Mean admission creatinine was 1.7 ± 1.6 mg/dl and 19% had a creatinine over 2 mg/dl. Serum creatinine increased more than 0.5 mg/dl during hospitalization in 9% of general patients and in 11% of diabetics. The increase in creatinine was associated with a higher risk of hospital mortality (odds ratio (OR) 12.9, 95% confidence intervals (CI) 6.7-27.6) and long term mortality (OR 2.1, 95% CI 1.6-3). Conclusions: The deterioration of renal function during hospitalization of patients with heart failure is a risk factor for hospital and long term mortality.

[Deterioration of kidney function as a risk factor for mortality among patients hospitalized for heart failure]. / Incidencia e importancia pronóstica del deterioro de la función renal en pacientes hospitalizados con insuficiencia cardiaca.

BACKGROUND: Acute deterioration of kidney function among patients admitted to the hospital for cardiac failure is associated with an increased mortality. AIM: To investigate the association between deterioration of kidney function and mortality among patients hospitalized for cardiac failure. MATERIAL AND METHODS: Patients admitted for decompensated cardiac failure to 14 Chilean hospitals between 2002 and 2009 were incorporated to the study. Clinical and laboratory features were registered. Serum creatinine values on admission and discharge were determined. Hospital and long term mortality was determined requesting death certificates to the National Identification Service at the end of follow up, lasting 635 ± 581 days. RESULTS: One thousand sixty four patients were incorporated and 1100, aged 68 ± 13 years (45% females) had information about renal function. Seventy seven percent were hypertensive and 36% were diabetic. Mean ejection fraction was 41 ± 18% and 34% had an ejection fraction over 50%. Mean admission creatinine was 1.7 ± 1.6 mg/dl and 19% had a creatinine over 2 mg/dl. Serum creatinine increased more than 0.5 mg/dl during hospitalization in 9% of general patients and in 11% of diabetics. The increase in creatinine was associated with a higher risk of hospital mortality (odds ratio (OR) 12.9, 95% confidence intervals (CI) 6.7-27.6) and long term mortality (OR 2.1, 95% CI 1.6-3). CONCLUSIONS: The deterioration of renal function during hospitalization of patients with heart failure is a risk factor for hospital and long term mortality.

[Heart energy metabolism and its role in the treatment of heart failure]. / Metabolismo energético del corazón y sus proyecciones en el tratamiento de la insuficiencia cardíaca.

It is unknown why heart failure progresses even when patients are treated with the best therapy available. Evidences suggest that heart failure progression is due to loss of neurohumoral blockade in advanced stages of the disease and to alterations in myocardial metabolism induced, in part, by this neurohumoral activation. Alterations in cardiac energy metabolism, especially those related to substrate utilization and insulin resistance, reduce the efficiency of energy production, causing a heart energy reserve deficit. These events play a basic role in heart failure progression. Therefore, modulation of cardiac metabolism has arisen as a promissory therapy in the treatment of heart failure. This review describes myocardial energy metabolism, evaluates the role of impaired energy metabolism in heart failure progression and describes new therapies for heart failure involving metabolic intervention.

Metabolismo energético del corazón y sus proyecciones en el tratamiento de la insuficiencia cardíaca / Heart energy metabolism and its role in the treatment of heart failure

It is unknown why heart failure progresses even when patients are treated with the best therapy available. Evidences suggest that heart failure progression is due to loss of neurohumoral blockade in advanced stages of the disease and to alterations in myocardial metabolism induced, in part, by this neurohumoral activation. Alterations in cardiac energy metabolism, especially those related to substrate utilization and insulin resistance, reduce the efficiency of energy production, causing a heart energy reserve deficit. These events play a basic role in heart failure progression. Therefore, modulation of cardiac metabolism has arisen as a promissory therapy in the treatment of heart failure. This review describes myocardial energy metabolism, evaluates the role of impaired energy metabolism in heart failure progression and describes new therapies for heart failure involving metabolic intervention.

Polución por material particulado fino (PM 2.5) incrementa las hospitalizaciones por insuficiencia cardiaca / Small particle air pollution (PM2.5) leads to an in crease in hospitalization rate for congestive heart failure

Antecedentes: Estudios recientes han reportado una asociación entre la contaminación ambiental por material particulado (PM) y el riesgo de hospitalizaciones de pacientes con insuficiencia cardiaca (IC). La región metropolitana de nuestro país constituye un área geográfica en la cual la contaminación es especialmente relevante, asociándose a incrementos periódicos en la morbimortalidad por causa respiratoria. Sin embargo el efecto de la polución por PM en la morbilidad de pacientes con IC no ha sido evaluado en forma sistemática. Objetivo: Evaluar la asociación entre el PM fino y las hospitalizaciones por IC descompensada en hospitales pertenecientes al registro ICARO del área metropolitana. Métodos: Estudio prospectivo. Entre enero 2002 a diciembre de 2008 se recolectaron las fichas médicas de 529 pacientes residentes de Santiago hospitalizados por IC descompensada. Las variables meteorológicas y de contaminación fueron obtenidas de la red MACAM. Para estudiar la asociación entre las hospitalizaciones y los niveles de contaminación (PM10 y PM2,5), se aplicó un diseño de Casos cruzados estratificado por tiempo (Time-stratified Case-crossover), controlando por temperatura y punto de rocío. El impacto de los niveles de contaminación en el número de hospitalizaciones se evaluó asumiendo una latencia en el efecto de la polución de 0 a 10 días. Resultados: La edad media de la población en estudio fue de 73.8 años. La etiología más frecuente fue isquémica (27 por ciento) e hipertensiva (27 por ciento). Un 73.2 por ciento de los pacientes eran hipertensos y 32.6 por ciento tenían antecedentes de diabetes mellitus. Se observó un aumento en la admisión por IC descompensada en pacientes de ambos sexos, menores de 74 años, con desde un 22.7 por ciento (p=0.03) por cada incremento en 10 ug/m3 de PM2.5 calculado con media móvil, cuatro días después de la exposición hasta un 44.8 por ciento (p=0.006) a 10 días de la exposición. Los pacientes con antecedentes de ...

Background: Recent studies have reported an increase risk of hospitalization in patients with congestive heart failure (CHF) in association with air pollution by small particles. The Metropolitan region in Chile is characterized by high pollution indexes which are related to increased mortality from respiratory diseases. No systematic evaluation of the effect of particle pollution upon morbidity in patients with CHF is available. Aim. To evaluate the association between fine particle pollution and hospitalization rate for decompensated CHF in hospitals participating in the ICARO registry of CHF in the Metropolitan area of Santiago. Methods. In a prospective design the clinical records of 529 patients who were hospitalized for decompensated CHF from Jan 2002 to Dec 2008 were analyzed Meteorological and pollution indexes were obtained from de MACAM monitoring network. A time stratified case cross-over design was used to study the association between hospitalization rate and pollution indexes (PM10 and PM25. Data was controlled for temperature and "punto de rocío" . A 0 to 10 day latency period was estimated to evaluate the influence of pollution on hospitalization rate. Results. The mean age of patients was 73.8 years. Etiologies for CHF included ischemic heart disease (27 percent) and hypertensive heart disease (27 percent). 73.2 percent of patients were hypertensives and 32.6 percent had evidence of DM. Hospitalization rate for CHF in men or women > 74 years of age increased from 22.7 percent 4 days after exposure to 44.8 percent 10 days after exposure (p=0.006). Diabetic patients were more susceptible to hospitalization with an 18 percent increased rate for each 10ug/m3 PM2.5 concentration at 8 days after exposure. Male and female hypertensive patients <74 years of age were also susceptible with a 28 percent (2.1 to 43/5 percent, CI) increase in hospitalization rate at 5 days after exposure. Conclusion: Patients with CHF who are diabetics or hy...

El tratamiento con atorvastatina reduce la actividad de xantina-oxidasa unida al endotelio en pacientes con insuficiencia cardíaca crónica: ¿un posible nuevo efecto pleiotrópico? / Treatment with atorvastatin reduces the activity of xanthine oxydase bound to endothelium in patients with chronic heart failure

El aumento en la actividad de la xantina-oxidasa unida al endotelio (XOec) puedeparticipar como un importante mediador de la disfunción endotelial en la insuficiencia cardíaca crónica (IC). Las estatinas son capaces de reducir el estrés oxidativo y restaurar la disfunción endotelial a través de mecanismos independientes de la reducción del colesterol. Sin embargo, el efecto de estos fármacos en la actividad de XOec es completamente desconocido. Nosotros estudiamos la hipótesis que atorvastatina durante 8 semanas reduce la actividad de XOec de manera independiente de los cambios en el colesterol. Metodología: Un total de 25 pacientes con IC (Fracción de eyección < 40 por ciento y Clase funcional NYHA II-III) recibieron placebo por 4 semanas, seguido por 8 semanas de atorvastatina 20 mg por día. Muestras desangre fueron recolectadas basalmente, 4 semanas y 12 semanas. La actividad de XOec y los niveles de ácido úrico fueron medidos por espectrofotometría.Resultados: El tratamiento con atorvastatina, pero no el placebo, redujo la actividad de ecXO (p<0.01), los niveles de ácido úrico (p<0.05), colesterol total (p<0.01), LDL-colesterol (p<0.01) y triglicéridos (p<0.05) sin cambios en los niveles de HDL-colesterol y creatinina. Además, no se encontraron correlaciones estadísticas entre la fracción de cambio de XOec y las fracciones de cambio de parámetros lipídicos. Conclusión: El efecto beneficioso a corto plazo de la atorvastatina en relación a la mejoría de la función endotelial demostrado en estudios previos, estaría asociado a una disminución en la actividad de XOec de una manera independiente a los cambios en el colesterol, lo que sugiere la presencia de un nuevo efecto pleiotrópico de las estatinas.

An increased activity of endothelium bound xanthine oxydase (XOeb) may play an important role as a mediator of endothelial dysfunction in chronic heart failure (CHF). Statins reduce oxydative stress and improve endothelial dysfunction through mechanisms unrelated to cholesterol lowering. However, the effect of statins on XOeb activity is unknown. We hypothesized that atorvastatin administered for 6 weeks would reduce XOeb independently of changes in serum cholesterol levels. Methods: 25 patients with CHF (NYHA class II or III with ejection fraction <40 percent received placebo for 4 weeks followed by atorvastatin, 20mg per day, for 8 weeks. Blood samples were obtained before statin administration and 4 and 12 weeks later. Spectrophotometry was used to determine XOeb and uric aced levels. Results: Atorvastatin, but not placebo, reduced XOeb activity (p<0.01), and uric acid (p<0.05), total cholesterol (p<0.01), LDL-cholesterol (p<0.01) and triglyceride levels (p<0.05). No changes were observed inHDL and creatinine levels. There was no correlation between XOeb changes and changes in the other lipid parameters. Conclusion: The known improvement in endothelial dysfuncion related to statin use previously reported is associated to a decrease in XOec activity independently of changes in cholesterol levels, suggesting a new pleiotropic effect of statins.

Gln(27)-->Glubeta(2)-adrenergic receptor polymorphism in heart failure patients: differential clinical and oxidative response to carvedilol.

We investigated the clinical response of chronic heart failure patients with beta(2)-adrenergic receptor Gln(27)-->Glu polymorphism treated for 6 months with carvedilol, a alpha/beta-antagonist with antioxidant properties. The 6-min. walk test, the left ventricular ejection fraction, heart rate, plasma norepinephrine and malondialdehyde, a stress oxidative marker, concentrations were evaluated at baseline and after treatment for 6 months with carvedilol in 33 stable chronic heart failure patients with the Gln(27)-->Glubeta(2)-adrenergic receptor polymorphism. Carvedilol significantly increased the left ventricular ejection fraction, while decreasing the heart rate and malondialdehyde plasma concentrations in chronic heart failure patients with the Glu(27)beta(2)-adrenergic receptor allele. There were however, no significant changes in patients with the Gln(27)beta(2)-adrenergic receptor variant.

Influencia de factores socioculturales en la evolución alejada de pacientes con insuficiencia cardíaca / Influence of social and cultural factors in the late course of patients with congestive heart failure

Objetivo: Evaluar el impacto de los factores socioculturales (SC) en Las características del cuidado de la insuficiencia cardiaca (IC) y la evolución post alta en pacientes admitidos con diagnostico de IC descompensada a hospitales del registro ICARO en el periodo 2006-2008.Método: Registro prospectivo de 14 hospitales. Se incorporaron en forma consecutiva pacientes admitidos con el diagnostico de IC descompensada entre enero 2006 y mayo 2008. La mortalidad al fin del seguimiento se determino por la base de datos del Servicio Nacional del Registro Civil e Identificación. Se definió como terapia optima la combinación de en betabloqueador con cualquiera de los siguientes: inhibidores de la enzima convertidora de angiotensina (IECA), antagonistas del receptor de angiotensina Il (ARAlI), hidralazina/isosorbide o espironolactona. Las características de los pacientes se compararon mediante t de Student o chi cuadrado según correspondía. La sobrevida se evaluó mediante Kaplan-Meier.Resultados: Los pacientes de bajo nivel SC son do mayor edad (71 +/- 11 v/s 66 +/-15 años respectivamente, p<0.01). predomina el género femenino (52.2 por ciento v/s 26.1 por ciento, p<0,01), y su previsión fue mayoritariamente FONASA (90 por ciento). La etiología isquémica fue más frecuente en el estrato SC alto (34,5 vs. 16,6 por ciento) y la hipertensiva en el nivel SC bajo (30,3 v/s 16,6 por ciento). La utilización de ARA II fue más frecuente en el nivel SC alto con una tendencia a menor utilización de IECA, el uso de betabloqueadores espironolactona hidralazina e isosorbide amiodarona y anticoagulante fue menor en el estrato SC bajo.

Aim: to evaluate de impact of social and cultural (S-C) factors in the care and course of patients with congestive heart failure (CHF) enrolled in the ICARO study (national registry for patients with head failure). Methods: Patients were enrolled from 2006 through 2008. They were discharged from 14 hospitals participating in the prospectively designed ICARO study. Late mortality was obtained from the national Identification registry. Optimal medical therapy was defined as the use of a betablocker in addition to any of the following ACE inhibitors, ARA II. combination of hydralazine and nitrates, or spironolactone. Statistical analysis included Students t tesl. chi square and Kaplan Meir and Log-rank testing, as appropriate. Results: Patients with a low S-C level were older (71 +/- 11 vs 66 +/- IS years. p<0.01). more frequently females (52.2 percent vs 26.1 percent, p<0.01) and most of them belonged in the FONASA health insurance system (90 percent). Ischemic heart disease was more prevalent in the high S-C level (34.5 vs 16.6 percent) and hypertension in the low S-C level (30.3 vs 16.6 percent). ARA II rather than ACE inhibitors were more commonly used in the high S-C level: A CE inhibitors, betablockers, spironolactone, hydralazine-nitrates, amiodarone and anticoagulatioo were less frequently used in the low S-C level. After discharge a more intensive treatment of heart failure was observed; however, this was less seen in the low S-C level. Patients with decreased left ventricular ejection fraction were similarly treated in both groups. An optimal therapy for CHF was used in 43.7 percent, 43.3 percent and 51.1 percent in S-C levels low, intermediate and high, respectively (NS). Independent predictors for late mortality were age>70 years (HR 2.71 (CI 1.55-3.03), low S-C level (HR 1.57, CII. 17- 2.09), EF<50 percent (HR 1.49, CI 1.04-2.14) and absence of optimal medical therapy at discharge (HR 0.52, CI 0.41-0.66).

Interacción entre los polimorfismos del receptor ß1 y ß2 adrenérgico como predictor de riesgo de insuficiencia cardiaca crónica / Interactions between ß1 and ß2 adrenergic receptor polymorphisms as risk factors for chronic heart failure

Background: ß adrenergic receptors (AR) are highly polymorphic and important regulators of cardiovascular homeostasis. Among these, ß1 and ß2 AR regulate cardiac contractility and frequency and are important pharmacological targets. Aim: To evaluate genotype and gene-gene interaction between ß1-AR Arg389Gly and ß2-AR ArglSGly GlnZ7Gly and Thrl 64Ile polymorphisms, as risk factors for HF. Material and methods: Eighty chronic HF patients and eighty-eight controls matched by age and sex were genotyped for ß1 -AR Arg389Gly ß2-AR ArgWGly, GlnZ7Glu and Thr164Ile polymorphisms. Results: The presence of ß2-AR Glu afiele was a risk predictor for HF (odds ratio (OR) =2.81; 95 percent confidence intervals (CI) =1.49-5.31). Interactions that increased the risk for HF were found in patients carrying at least one of the ß2-AR Glu and ß2-AR Gly allele (OR =3.81; 95 percent CI =1.50-0.70) and ß2-AR Glu and ß1 -AR Gly allele combination (OR =5.51; 95 percent CI =2.19-13.86). Furthermore, the frequency of ß2-AR Glu allele was higher among patients with a history ofacute myocardial infarction (with infarction: 0.534, without: 0.313, p =0.01). Conclusions: ß2-AR Glu allele could be a risk predictor for HF. This risk could be enhanced by the additional presence of ß2-AR GlyW or ß1-AR Arg389 alleles. The frequency of ß2-AR Gln27 Glu allele was higher among patients with a history of myocardial infarction.

[Inflammation and endothelial dysfunction in patients with chronic heart failure]. / Inflamación y disfunción endotelial en pacientes con insuficiencia cardiaca crónica.

BACKGROUND: In chronic heart failure (CHF), endothelial dysfunction (ED) is a consequence of an imbalance of vascular tone regulating substances. The relationship between ED and inflammation has not been fully investigated. AIM: To assess the association between inflammation and ED in CHF. MATERIAL AND METHODS: Forty two patients aged 56+/-14 years (80% male) with a CHF in functional capacity II-III (New York Heart Association) and an ejection fraction (FE) <40% were consecutively studied. Patients were classified according to the presence or absence of ED, evaluated by reactive vasodilation measured by ultrasound, after brachial artery compression. Circulating levels of highly sensitive C reactive protein (usCRP), tumor necrosis factor a (TNFá) and interleukin-6 (IL-6) were determined by ELISA. A group of 15 healthy subjects of similar age, were studied as controls. RESULTS: Sixty seven percent of patients had ED. Compared to controls, patients with CHF had higher usCRP (0.58+/-0.4 and 4.9+/-7.1 mg/dl respectively, p <0.01) and IL-6 (1.38+/-0.06 and 3.1+/-1.7 mg/dl respectively, p <0.01). Compared to patients without ED, patients with CHF and ED had higher levels of usCRP (3.0+/-0.4 and 6.0+/-5.7 mg/dl respectively, p <0.01) and TNFá (0.31+/-0.26 and 1.0+/-1.1 pg/ml, p =0.02). No differences in IL-6 were found between CHF groups. CONCLUSIONS: In CHF patients, the presence of ED was associated with increased levels of inflammatory markers.

Serum uric acid correlates with extracellular superoxide dismutase activity in patients with chronic heart failure.

Increased serum uric acid has been identified as an independent risk factor for cardiovascular disease. However, because of its antioxidant capacity, uric acid may play a beneficial role in endothelial function. This paradoxical relationship between uric acid and endothelial function in chronic heart failure patients remains poorly understood. Thirty-eight chronic heart failure patients (New York Heart Association functional class II-III, mean age 58+/-10 years and mean left ventricular ejection fraction 25+/-8%) and twelve age-and-sex-matched healthy controls were studied. Chronic heart failure patients showed higher uric acid levels (7.3+/-2.3 mg/dL vs. 6.1+/-0.2 mg/dL, p<0.05) and lower extracellular superoxide dismutase activity (136+/-36 U ml(-1) min(-1) vs. 203+/-61 U ml(-1) min(-1), p<0.01) and endothelium-dependent vasodilatation (4.0+/-1.6% v. 9.1+/-3.0%, p<0.01) when compared with control subjects. In chronic heart failure patients, correlations between both uric acid levels and extracellular superoxide dismutase activity (r=0.45; p<0.01), and uric acid and endothelium-dependent vasodilatation (r=0.35; p=0.03) were detected. These correlations were not observed in healthy individuals, suggesting a positive effect of uric acid on endothelial function partially mediated by modulation of extracellular superoxide dismutase activity in chronic heart failure.

Inflamación y disfunción endotelial en pacientes con insuficiencia cardiaca crónica / Inflammation and endothelial dysfunction in patients with chronic heart failure

Background: In chronic heart failure (CHF), endothelial dysfunction (ED) is a consequence of an imbalance of vascular tone regulating substances. The relationship between ED and inflammation has not been fully investigated. Aim: To assess the association between inflammation and ED in CHF. Material and methods: Forty two patients aged 56±14 years (80 percent male) with a CHF in functional capacity II-III (New York Heart Association) and an ejection fraction (FE) <40 percent were consecutively studied. Patients were classified according to the presence or absence of ED, evaluated by reactive vasodilation measured by ultrasound, after brachial artery compression. Circulating levels of highly sensitive C reactive protein (usCRP), tumor necrosis factor a (TNFá) and interleukin-6 (IL-6) were determined by ELISA. A group of 15 healthy subjects of similar age, were studied as controls. Results: Sixty seven percent of patients had ED. Compared to controls, patients with CHF had higher usCRP (0.58±0.4 and 4.9±7.1 mg/dl respectively, p <0.01) and IL-6 (1.38±0.06 and 3.1±1.7 mg/dl respectively, p <0.01). Compared to patients without ED, patients with CHF and ED had higher levéis of usCRP (3.0±0.4 and 6.0±5.7 mg/dl respectively, p <0.01) and TNFá (0.31±0.26 and 1.0±1.1 pg/ml, p =0.02). No differences in IL-6 were found between CHF groups. Conclusions: In CHF patients, the presence of ED was associated with increased levéis of inflammatory markers.

Pleiotropic effects of atorvastatin in heart failure: role in oxidative stress, inflammation, endothelial function, and exercise capacity.

BACKGROUND: Increased oxidative stress, a common feature in chronic heart failure, has been associated with inflammation, endothelial dysfunction, and extracellular matrix degradation. Statins have known anti-inflammatory and anti-oxidant effects; however, their role in chronic heart failure is still controversial. METHODS: This was a prospective study of 38 patients with stable systolic chronic heart failure. Patients received a 4-week placebo course, followed by atorvastatin 20 mg/day for 8 weeks. Oxidative stress, inflammation and remodeling markers, brachial artery flow-mediated vasodilation, and 6-minute walk test were evaluated at baseline, 4, and 8 weeks. RESULTS: Mean age was 58 +/- 12. Mean left ventricular ejection fraction was 27% +/- 12%. No significant differences were observed between measurements at baseline and after placebo. Atorvastatin induced a significant decrease of matrix metalloproteinase-9 activity, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-6, and malondialdehyde, and a significant increase of endothelial superoxide dismutase activity when compared with placebo. No differences in tissue inhibitor of matrix metalloproteinase and matrix metalloproteinase-2 activities were observed. Atorvastatin use was associated with an improved flow-dependent brachial vasodilation and exercise capacity in the 6-minute walk test. CONCLUSIONS: In chronic heart failure patients, atorvastatin therapy is associated with a decrease of inflammation and extracellular matrix remodeling, improving both endothelial function and exercise capacity.

[Interactions between beta1 and beta2 adrenergic receptor polymorphisms as risk factors for chronic heart failure]. / Interacción entre los polimorfismos del receptor beta1, y beta2 adrenérgico como predictor de riesgo de insuficiencia cardiaca crónica.

BACKGROUND: Beta adrenergic receptors (AR) are highly polymorphic and important regulators of cardiovascular homeostasis. Among these, beta1 and beta2 AR regulate cardiac contractility and frequency and are important pharmacological targets. AIM: To evaluate genotype and gene-gene interaction between beta1-AR Arg389Gly and beta2-AR Arg16Gly, Gln27Glu and Thr164Ile polymorphisms, as risk factors for HF. MATERIAL AND METHODS: Eighty chronic HF patients and eighty-eight controls matched by age and sex were genotyped for beta1-AR Arg389Gly, beta2-AR Arg16Gly, Gln27Glu and Thr164Ile polymorphisms. RESULTS: The presence of beta2-AR Glu allele was a risk predictor for HF (odds ratio (OR) = 2.81; 95% confidence intervals (CI) = 1.49-5.31). Interactions that increased the risk for HF were found in patients carrying at least one of the beta2-AR Glu and beta2-AR Gly allele (OR = 3.81; 95% CI = 1.50-0.70) and beta2-AR Glu and beta1-AR Gly allele combination (OR = 5.51; 95% CI = 2.19-13.86). Furthermore, the frequency of beta2-AR Glu allele was higher among patients with a history of acute myocardial infarction (with infarction: 0.534, without: 0.313, p = 0.01). CONCLUSIONS: Beta2-AR Glu allele could be a risk predictorfor HF. This risk could be enhanced by the additional presence of beta2-AR Gly16 or beta1-AR Arg389 alleles. The frequency of beta2-AR Gln27 Glu allele was higher among patients with a history of myocardial infarction.

Superóxido dismutasa ligada al endotelio es un sensible marcador de estrés oxidativo y disfunción endotelial en la insuficiencia cardíaca / Endothelial linked superoxide dismutase is a sensitive marker of oxidative stress and endothelial dysfunction in patients with congestive heart failure

Introducción: En pacientes con insuficiencia cardíaca (IC) existe activación neurohumoral que contribuye a la progresión clínica de la enfermedad y se ha asociado a aumento del estrés oxidativo (EO) y deterioro de la capacidad funcional. Pacientes con IC avanzada tienen niveles aumentados de malodihaldehido, un marcador de EO, pero niveles normales de enzimas antioxidantes. En la pared vascular, la enzima superóxido dismutasa ligada a endotelio (SODec) representa un importante sistema enzimático antioxidante que contribuye a la inactivación de especies reactivas del oxígeno (ROS) y a la modulación del tono vascular. Objetivo: Estudiar el rol de SODec como marcador de EO en IC y su correlación con la función endotelial. Métodos: Estudiamos 20 pacientes con IC moderada (Clase II-III) con fracción de eyección de ventrículo izquierdo (FEVI) < 40 por ciento. Se determinaron los niveles plasmáticos de MDA por sustancias reactivas del ácido tiobarbitúrico y los sistemas de defensa antioxidantes eritrocitarios SOD y catalasa (CAT) por espectofotometría. La enzima ecSOD se liberó de la superficie endotelial mediante la administración de heparina en bolo (5000 U) en la arteria braquial determinando su actividad en sangre venosa. La función endotelial se determinó mediante ecografía de arteria braquial para determinar la vasodilatación dependiente de endotelio. Se utilizó un grupo control de personas sanas pareadas por edad y sexo. Los resultados se expresan como promedio ± DES y en el análisis estadístico se utilizó t-Student y correlación lineal de Pearson. Resultados: Edad promedio de 59 ± 16 años, 17 hombres (85 por ciento). Nueve con etiología isquémica (45 por ciento). La FEVI fue de 33 ± 5 por ciento, el test de caminata de 6 minutos de 412 ± 90 m. Los niveles plasmáticos de MDA y de SOD y CAT eritrocitarios fueronsimilares en pacientes con IC y en grupo control. En los pacientes con IC encontramos una disminución significativa de la actividad de SODec (p< 0.001)...

Effects of carvedilol on oxidative stress and chronotropic response to exercise in patients with chronic heart failure.

BACKGROUND: Our previous studies suggest that the increase in heart rate from rest to peak exercise is reduced in patients with chronic heart failure (CHF) and this is associated with increased oxidative stress, as determined by malondialdehyde (MDA) plasma levels. AIM: To investigate the effects of carvedilol on the heart rate response to exercise and oxidative stress in patients with CHF. METHODS AND RESULTS: Thirty stable NYHA classes II-III CHF patients received carvedilol therapy for 6 months, at a mean maintenance dose of 25 mg (range 6.25-50 mg/day). After treatment, the patients showed a significant improvement in their functional NYHA class (p=0.013), increased left ventricular ejection fraction (LVEF) (24+/-1.4% to 31+/-2.3%, p=0.003) and 6-min walk distance (499+/-18 to 534+/-18 m, p=0.03), without changes in the peak VO2. At baseline, norepinephrine (NE) plasma levels increased with exercise (510+/-51 to 2513+/-230 pg/mL, p<0.001), and these levels were not affected by carvedilol. Chronotropic responsiveness index (increase in heart rate divided by the increase in NE from rest to peak exercise) was not changed by carvedilol (0.049+/-0.001 to 0.042+/-0.001, p=0.6). MDA levels of CHF patients decreased after treatment with carvedilol (2.4+/-0.2 to 1.1+/-0.2 microM, p<0.001), without changes in antioxidant enzyme activities. CONCLUSIONS: Carvedilol treatment in patients with CHF results in reduced oxidative stress without restoration of the chronotropic responsiveness index.