Dietary Fiber Modulates the Release of Gut Bacterial Products Preventing Cognitive Decline in an Alzheimer's Mouse Model.

Fiber intake is associated with a lower risk for Alzheimer´s disease (AD) in older adults. Intake of plant-based diets rich in soluble fiber promotes the production of short-chain fatty acids (SCFAs: butyrate, acetate, propionate) by gut bacteria. Butyrate administration has antiinflammatory actions, but propionate promotes neuroinflammation. In AD patients, gut microbiota dysbiosis is a common feature even in the prodromal stages of the disease. It is unclear whether the neuroprotective effects of fiber intake rely on gut microbiota modifications and specific actions of SCFAs in brain cells. Here, we show that restoration of the gut microbiota dysbiosis through the intake of soluble fiber resulted in lower propionate and higher butyrate production, reduced astrocyte activation and improved cognitive function in 6-month-old male APP/PS1 mice. The neuroprotective effects were lost in antibiotic-treated mice. Moreover, propionate promoted higher glycolysis and mitochondrial respiration in astrocytes, while butyrate induced a more quiescent metabolism. Therefore, fiber intake neuroprotective action depends on the modulation of butyrate/propionate production by gut bacteria. Our data further support and provide a mechanism to explain the beneficial effects of dietary interventions rich in soluble fiber to prevent dementia and AD. Fiber intake restored the concentration of propionate and butyrate by modulating the composition of gut microbiota in male transgenic (Tg) mice with Alzheimer´s disease. Gut dysbiosis was associated with intestinal damage and high propionate levels in control diet fed-Tg mice. Fiber-rich diet restored intestinal integrity and promoted the abundance of butyrate-producing bacteria. Butyrate concentration was associated with better cognitive performance in fiber-fed Tg mice. A fiber-rich diet may prevent the development of a dysbiotic microbiome and the related cognitive dysfunction in people at risk of developing Alzheimer´s disease.

Expression of VEGF- and tight junction-related proteins in the neocortical microvasculature of patients with drug-resistant temporal lobe epilepsy.

The blood-brain barrier (BBB) maintains the optimal microenvironment for brain function. Tight junctions (TJs) allow endothelial cells to adhere to each other, leading to the formation of a barrier that prevents the penetration of most molecules via transcellular routes. Evidence has indicated that seizure-induced vascular endothelial growth factor (VEGF) type 2 receptor (VEGFR-2) pathway activation weakens TJs, inducing vasodilatation and increasing vascular permeability and subsequent brain injury. The present study focused on investigating the expression levels of VEGF-related (VEGF-A and VEGFR-2) and TJ-related proteins (claudin-5, occludin and ZO-1) in the neocortical microvasculature of patients with drug-resistant temporal lobe epilepsy (TLE). The results obtained from hippocampal sclerosis TLE (HS-TLE) patients were compared with those obtained from patients with TLE secondary to lesions (lesion-TLE) and autopsy samples. The Western blotting and immunofluorescence results showed that VEGF-A and VEGFR-2 protein expression levels were increased in HS-TLE and lesion-TLE patients compared to autopsy group. On the other hand, claudin-5 expression was higher in HS-TLE patients and lesion-TLE patients than autopsies. The expression level of occludin and ZO-1 was decreased in HS-TLE patients. Our study described modifications to the integrity of the BBB that may contribute to the pathogenesis of TLE, in which the VEGF system may play an important role. We demonstrated that the same modifications were present in both HS-TLE and lesion-TLE patients, which suggests that seizures modify these systems and that they are not associated with the establishment of epilepsy.

The nuclear receptor FXR, but not LXR, up-regulates bile acid transporter expression in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Patients with non-alcoholic steatohepatitis (NASH) have increased plasmatic and hepatic concentrations of bile acids (BA), suggesting that they can be associated with the progression of the disease. Hepatic nuclear receptors are known to modulate genes controlling BA metabolism; thus, in this work we aimed to compare the expression of liver nuclear receptors -farnesoid X (FXR), small heterodimer partner (SHP) and liver X alpha (LXRα) receptors- and BA transporters -sodium+/taurocholate cotransporting polypeptide (NTCP) and bile salt export pump (BSEP)- in liver biopsy samples of patients with simple steatosis (SS) and NASH. MATERIAL AND METHODS: Forty patients with biopsy-proven NALFD were enrolled between 2009 and 2012; liver biopsies were classified as SS (N = 20) or NASH (N = 20) according to the NAFLD activity score. Gene expression of nuclear FXR, LXRα, SHP, NTCP and BSEP was analyzed by real-time reverse transcription polymerase chain reaction and protein level was quantified by western blot. RESULTS: Gene expression of FXR, SHP, NTCP and BSEP was significantly up-regulated in the NASH group in comparison with SS patients (P < 0.05). In contrast, protein level for FXR, SHP and NTCP was decreased in the NASH patients vs. the SS group (P < 0.05). Gene and protein profile of LXRα did not show differences between groups. CONCLUSIONS: The results suggest that liver nuclear receptors (FXR and SHP) and BA transporters (NTCP and BSEP) are associated with the progression of NAFLD.

A metal mixture induces transformation upon antioxidant depletion in a hepatic cell line.

INTRODUCTION: Metals are ubiquitous soil, air, and water pollutants. A mixture of arsenic cadmium and lead, in particular, has commonly been found in the vicinity of smelter areas. The mixture of As-Cd-Pb has been shown to be carcinogenic, and transforming potential and oxidative stress have been proposed as principal mechanisms involved in this process. The aim of this work was to explore the role of the antioxidant barrier in the establishment of cell transformation upon chronic exposure to a metal mixture containing 2 µM NaAsO(2), 2 µM. CdCl(2), and 5 µM Pb(C(2)H(3)O(2))(2)∙3H(2)O in WRL-68 cells-a non-transformed human hepatic cell line. MATERIAL AND METHODS: In this study, we used a WRL-68 cell model of human embryonic hepatic origin treated with antioxidant inhibitors (L-Buthionine-sulfoxamine and aminotriazole) to test the role of the antioxidant barrier in the establishment of cell transformation upon chronic exposure to a metal mixture of As-Cd-Pb (2 µM NaAsO(2), 2 µM CdCl(2) and 5 µM Pb(C(2)H(3)O(2))(2)∙3H(2)O). We evaluated oxidative damage markers, including reactive oxygen species, lipid peroxidation, and genotoxicity, as well as antioxidant response markers, including glutathione concentration, catalase activity, and superoxide dismutase activity, which promote morphological transformation, which can be quantified by foci formation. RESULTS: As expected, we found an increase in the intracellular concentration of the metals after treatment with the metal mixture. In addition, treatment with the metal mixture in addition to inhibitors resulted in a large increase in the intracellular concentration of cadmium and lead. Our results describe the generation of reactive oxygen species, cytotoxicity, genotoxicity, and oxidative damage to macromolecules that occurred exclusively in cells that were morphologically transformed upon exposure to a metal mixture and antioxidant barrier inhibition. CONCLUSION: Our results show the importance of the antioxidant barrier role in the protection of cellular integrity and the transformation potential of this metal mixture via free radicals.

Bilirubin alone as a biomarker for short-term mortality in acute-on-chronic liver failure: an important prognostic indicator.

BACKGROUND AND AIMS. Acute-on-chronic liver failure has been recognized as a sudden deterioration of cirrhosis, with a high short-term mortality. Prognostic scores are used to assess liver dysfunction. However, there is not enough information on a score to predict short term mortality in those patients. We aimed to investigate the prognostic value of bilirubin concentration in predicting the 1-week outcome of patients with acute-on-chronic liver failure. MATERIAL AND METHODS. We performed a retrospective analysis with a cohort of 65 patients (33 women/32 men), age average of 64 years, diagnosed with acute-on-chronic liver failure with at least 1 week follow-up. Demographics, clinical and biochemical variables were analyzed. Most patients died (59 %) within 1 week of follow-up. RESULTS. In univariate logistic regression analysis, admission to the intensive care unit, use of vasoactive drugs, need for parenteral nutrition, and levels of conjugated, unconjugated, and total bilirubin at the time of hospital admission were significantly associated with 1-week mortality; in a multivariate logistic regression, conjugated (p = 0.01), unconjugated (p =0.01), and total bilirubin (p = 0.009) were independently associated with 1-week mortality. In ROC curve analysis, conjugated (0.751, p < 0.05) and total bilirubin (0.746, p < 0.05) levels were significantly the best short-term mortality predictors. CONCLUSIONS. High levels of bilirubin are able to predict short-term mortality in these patients. Also, we suggest that bilirubin can be used as a biochemical marker to improve triage of patients with acute-on-chronic liver failure especially with emerging interventions such as extracorporeal liver assist devices and possibly improved early phase pharmacological therapies.

Metabolic syndrome and nonalcoholic fatty liver disease. The role of endothelial progenitor cells.

BACKGROUND: Endothelial dysfunction has been previously described in metabolic syndrome patients. The levels of circulating endothelial progenitor cells (EPCs) inversely correlates with the incidence of cardiovascular disease. The aim of this study was to investigate the association between NAFLD, metabolic syndrome and EPC levels. MATERIAL AND METHODS: A cross-sectional pilot study was performed at a university hospital in Mexico. Two groups of patients without previously known chronic diseases were studied and classified according to the presence of NAFLD. Anthropometric, dietary, and biochemical variables, and circulating EPC number were measured and compared between the groups. RESULTS: Forty subjects were included and classified into two groups: patients with NAFLD (n = 20) and a control group (n = 20). The overall prevalence of insulin resistance and metabolic syndrome was 25% and 17.5%, respectively. EPC levels were found to be higher in the NAFLD group (p < 0.05) as in the patients with insulin resistance (p < 0.01) and metabolic syndrome (p < 0.01). These levels showed correlation with the severity of steatosis. CONCLUSIONS: Patients with NAFLD have increased levels of EPC, such levels are associated with the severity of NAFLD. These findings may suggest that these cells may play a role in the early natural history of NAFLD. EPC might be increased in an attempt to repair the endothelial damage resulting from metabolic alterations accompanying NAFLD. Further studies are needed to establish the dynamics of these cells in NAFLD.

High coffee intake is associated with lower grade nonalcoholic fatty liver disease: the role of peripheral antioxidant activity.

BACKGROUND & AIMS: Some phytochemicals present in coffee have a potential antioxidant role which seems to protect the human body against cardiovascular diseases, liver disease and malignancies. Nonalcoholic fatty liver disease is a common disease with limited therapeutic options. This study investigated the antioxidant effect of coffee by measuring antioxidant enzymes and lipid peroxidation markers in patients with nonalcoholic fatty liver disease. MATERIAL AND METHODS: We performed a case-control study at the University Hospital, Mexico City. Anthropometric, metabolic, dietary and biochemical variables of all patients were determined and compared. The presence of nonalcoholic fatty liver disease was established by ultrasonography. All patients completed a dietary questionnaire in order to determine their of coffee consumption. Catalase, superoxide dismutase and thiobarbituric acid reactive substances were measured in all of the patients. RESULTS: Seventy-three subjects with and 57 without nonalcoholic fatty liver disease were included. Patients with nonalcoholic fatty liver disease had significantly higher body mass index, blood glucose, homeostasis model of assessment-insulin resistance and insulin values in comparison to patients without nonalcoholic fatty liver disease. On the one hand, there was a significant difference in coffee intake between the groups (p < 0.05, for all comparisons). There was no significant difference between groups in catalase (0.39 ± 0.74 vs. 0.28 ± 0.69 nM/min/mL), superoxide dismutase (5.4 ± 3.45 vs. 4.7 ± 2.1 U/mL) or thiobarbituric acid-reactive substances (4.05 ± 1.87 vs. 3.94 ± 1.59 µM/mL). CONCLUSIONS: A high intake of coffee has a protective effect against nonalcoholic fatty liver disease however there was no significant difference in the antioxidant variables analyzed.

Protective Effect of Tilia americana var. mexicana Against Kainic Acid-induced Damage in Brain, Liver, and Kidney: Behavioral and Biochemical Changes.

Tiliaamericana var. mexicana (Tilia) possesses anticonvulsant, antioxidant, neuroprotective, and hepatoprotective activities. The spectrum of anticonvulsant activity in status epilepticus models has not been sufficiently explored. We evaluated the effects of ethyl acetate (EAc), and methanol (ME) extracts on kainic acid (KA)-induced seizures by measuring rats'behavior (severity and latency) and lipoperoxidation in different brain areas (cerebellum, brain hemispheres, cortex, and medulla), kidneys, and liver. Male Wistar rats were administered KA (10 mg/kg, i.p.) after three days of pretreatment with Tilia extract (100 mg/kg). The EAc and ME Tilia extracts significantly decreased the severity of phase 1 and phase 2 seizures, respectively. The ME Tilia extract increased the latency to seizure (27 ± 2 min) compared to the control (13 ± 2 min). The ME and EAc Tilia extracts significantly prevented the increased lipid peroxidation caused by KA-induced seizures in the cerebellum, brain hemispheres, cortex, medulla, liver, and kidneys. The vehicle olive oil (OO) also showed anticonvulsant effects, decreasing the severity of seizures to phase 3 and lipoperoxidation levels in the cerebellum, brain hemispheres, cortex, medulla, liver, and kidneys. The anticonvulsant activity of Tilia is mediated by antioxidant effects in central and systemic areas that involve synergistic interactions among the chemical constituents of these extracts (glucosides of quercetin and kaempferol), while vehicle OO showed the same effects, probably due to its constituent oleuropein.

Exposure to Sub-Lethal Doses of Permethrin Is Associated with Neurotoxicity: Changes in Bioenergetics, Redox Markers, Neuroinflammation and Morphology.

Permethrin (PERM) is a member of the class I family of synthetic pyrethroids. Human use has shown that it affects different systems, with wide health dysfunctions. Our aim was to determine bioenergetics, neuroinflammation and morphology changes, as redox markers after subacute exposure to PERM in rats. We used MDA determination, protein carbonyl assay, mitochondrial O2 consumption, expression of pro-inflammatory cytokines and a deep histopathological analysis of the hippocampus. PERM (150 mg/kg and 300 mg/kg body weight/day, o.v.) increased lipoperoxidation and carbonylated proteins in a dose-dependent manner in the brain regions. The activities of antioxidant enzymes glutathione peroxidase, reductase, S-transferase, catalase, and superoxide dismutase showed an increase in all the different brain areas, with dose-dependent effects in the cerebellum. Cytokine profiles (IL-1ß, IL-6 and TNF-α) increased in a dose-dependent manner in different brain tissues. Exposure to 150 mg/kg of permethrin induced degenerated and/or dead neurons in the rat hippocampus and induced mitochondrial uncoupling and reduction of oxidative phosphorylation and significantly decreased the respiratory parameters state 3-associated respiration in complex I and II. PERM exposure at low doses induces reactive oxygen species production and imbalance in the enzymatic antioxidant system, increases gene expression of pro-inflammatory interleukins, and could lead to cell damage mediated by mitochondrial functional impairment.

[Biomarkers for detection and prediction in acute coronary syndrome]. / Biomarcadores de detección y predicción de síndrome coronario agudo.

Diagnosis of patients with suggestive symptoms of acute coronary syndrome (ACS), in an emergency department, is problematic. Troponine or CKMB are the gold standard biochemical markers to diagnose the ACS, and the clinical practice guidelines of the various scientific societies recommend their use with the best available evidence. Other biomarkers such as myoglobin, hs-PCR and natriuretic peptides, support the diagnosis of ACS although its recognition in clinical practice guidelines has a lower level of evidence. New biomarkers with sufficient reliability would be necessary to anticipate the clinical presentation of the entity. There are biomarkers such as inflammatory cytokines, cellular adhesion molecules, acute-phase reactants, plaque destabilization and rupture biomarkers, markers of myocardial ischemia and stretch, that may provide earlier assessment of the overall risk of the patient and help identify future events. Possibly, its clinical use would decrease the number of consultations in the emergency department and help prevent future adverse effects. The objective of this review is to study the potential clinical utility of new biomarkers of risk stratification in patients with ACS, as well as deepen the knowledge of the pathophysiology of this syndrome.

[Body mass index in the prognosis of first myocardial infarction]. / Índice de masa corporal como factor pronóstico en pacientes tras un primer infarto de miocardio.

BACKGROUND AND OBJECTIVES: The value of body mass index in the prognosis of patients with ischemic heart disease is not well defined. The objective of our study was to determine the association of body mass index with classic and emergent cardiovascular risk factors and with intra-hospital and 6-months mortality. PATIENTS AND METHODS: We conducted a prospective, multicenter study with a 6-months follow-up. We included 1063 patients between the ages of 25-75 years old who were consecutively admitted to the hospital within the first 24 hours of the onset of symptoms between years 2001 and 2003. We determined demographic and anthropometric variables, as well as classic and emergent factors of risk, clinical variables and the treatment administered. We carried out a univariate and multivariate analysis. RESULTS: The percentage of patients with overweight or obesity in this population was 73.56%. Overweight and obesity were associated with classical risk factors, except for smoking, and emergent risk factors. Body mass index was not associated with short-or mid-term prognosis. CONCLUSIONS: Body mass index is not a useful anthropometric measure to determine the prognosis of patients after a first myocardial infarction.

Drug-Resistant Temporal Lobe Epilepsy Alters the Expression and Functional Coupling to Gαi/o Proteins of CB1 and CB2 Receptors in the Microvasculature of the Human Brain.

Cannabinoid receptors 1 and 2 (CB1 and CB2, respectively) play an important role in maintaining the integrity of the blood-brain barrier (BBB). On the other hand, BBB dysfunction is a common feature in drug-resistant epilepsy. The focus of the present study was to characterize protein expression levels and Gαi/o protein-induced activation by CB1 and CB2 receptors in the microvascular endothelial cells (MECs) isolated from the brain of patients with drug-resistant mesial temporal lobe epilepsy (DR-MTLE). MECs were isolated from the hippocampus and temporal neocortex of 12 patients with DR-MTLE and 12 non-epileptic autopsies. Immunofluorescence experiments were carried out to determine the localization of CB1 and CB2 receptors in the different cell elements of MECs. Protein expression levels of CB1 and CB2 receptors were determined by Western blot experiments. [35S]-GTPγS binding assay was used to evaluate the Gαi/o protein activation induced by specific agonists. Immunofluorescent double-labeling showed that CB1 and CB2 receptors colocalize with tight junction proteins (claudin-5, occludin, and zonula occludens-1), glial fibrillary acidic protein and platelet-derived growth factor receptor-ß. These results support that CB1 and CB2 receptors are expressed in the human isolated microvessels fragments consisting of MECs, astrocyte end feet, and pericytes. The hippocampal microvasculature of patients with DR-MTLE presented lower protein expression of CB1 and CB2 receptors (66 and 43%, respectively; p < 0.001). However, its Gαi/o protein activation was with high efficiency (CB1, 251%, p < 0.0008; CB2, 255%, p < 0.0001). Microvasculature of temporal neocortex presented protein overexpression of CB1 and CB2 receptors (35 and 41%, respectively; p < 0.01). Their coupled Gαi/o protein activation was with higher efficiency for CB1 receptors (103%, p < 0.006), but lower potency (p < 0.004) for CB2 receptors. The present study revealed opposite changes in the protein expression of CB1 and CB2 receptors when hippocampus (diminished expression of CB1 and CB2) and temporal neocortex (increased expression of CB1 and CB2) were compared. However, the exposure to specific CB1 and CB2 agonists results in high efficiency for activation of coupled Gαi/o proteins in the brain microvasculature of patients with DR-MTLE. CB1 and CB2 receptors with high efficiency could represent a therapeutic target to maintain the integrity of the BBB in patients with DR-MTLE.

Dose-Dependent Behavioral and Antioxidant Effects of Quercetin and Methanolic and Acetonic Extracts from Heterotheca inuloides on Several Rat Tissues following Kainic Acid-Induced Status Epilepticus.

Kainic acid (KA) has been used to study the neurotoxicity induced after status epilepticus (SE) due to activation of excitatory amino acids with neuronal damage. Medicinal plants can protect against damage caused by KA-induced SE; in particular, organic extracts of Heterotheca inuloides and its metabolite quercetin display antioxidant activity and act as hepatoprotective agents. However, it is unknown whether these properties can protect against the hyperexcitability underlying the damage caused by KA-induced SE. Our aim was to study the protective effects (with regard to behavior and antioxidant activity) of administration of natural products methanolic (ME) and acetonic (AE) extracts and quercetin (Q) from H. inuloides at doses of 30 mg/kg (ME30, AE30, and Q30 groups), 100 mg/kg (ME100, AE100, and Q100 groups), and 300 mg/kg (ME300, AE300, and Q300 groups) against damage in brain regions of male Wistar rats treated with KA. We found dose-dependent effects on behavioral and biochemical studies in the all-natural product groups vs. the control group, with decreases in seizure severity (Racine's scale) and increases in seizure latency (p < 0.05 in the ME100, AE100, Q100, and Q300 groups and p < 0.01 in the AE300 and ME300 groups); on lipid peroxidation and carbonylated proteins in all brain tissues (p < 0.0001); and on GPx, GR, CAT, and SOD activities with all the treatments vs. KA (p ≤ 0.001). In addition, there were strong negative correlations between carbonyl levels and latency in the group treated with KA and in the group treated with methanolic extract in the presence of KA (r = -0.9919, p = 0.0084). This evidence suggests that organic extracts and quercetin from H. inuloides exert anticonvulsant effects via direct scavenging of reactive oxygen species (ROS) and modulation of antioxidant enzyme activity.

Estimated creatinine clearance: a determinant prognostic factor in heart failure.

BACKGROUND AND OBJECTIVE: Patients with heart failure and overt kidney failure (KF) have poor prognosis. Even mild degrees of kidney dysfunction might have prognostic value. The aim was to assess whether creatinine clearance values estimated with Cockroft formula correlated with survival at 2 years of follow-up in an outpatient heart failure unit population. PATIENTS AND METHOD: 423 patients (72% men), with a mean (standard deviation) age of 65.5 (11) years, were studied. Etiology of heart failure was mainly ischemic heart disease (59.6%). Mean left ventricle ejection fraction was 32.3% (13.3%). Patients were grouped according to stages of chronic kidney disease: $ 90 ml/min; 89-60 ml/min; 59-30 ml/min; 29-15 ml/min, and < 15 ml/min or on dialysis. KF was defined as creatinine clearance < 60 ml/min. RESULTS: Prevalence of KF was 52%. Mortality at 2 years was 3.2% in patients with creatinine clearance >or= 90 ml/min; 13.7% between 89-60 ml/min; 23.7% between 59-30 ml/min; 51% between 29-15 ml/min and 80% in patients with creatinine clearance < 15 ml/min or on dialysis (p < 0.001). Mortality was 30.4% in patients with KF and 10.3% in those without it (p < 0.001). CONCLUSIONS: Creatinine clearance values estimated by Cockroft formula had a highly predictive prognostic value in patients with heart failure. Even mild degrees of kidney function impairment showed higher mortality than normal kidney function values.

Expression and localization of the polarity protein CRB2 in adult mouse brain: a comparison with the CRB1rd8 mutant mouse model.

Acquisition of cell polarization is essential for the performance of crucial functions, like a successful secretion and appropriate cell signaling in many tissues, and it depends on the correct functioning of polarity proteins, including the Crumbs complex. The CRB proteins, CRB1, CRB2 and CRB3, identified in mammals, are expressed in epithelial-derived tissues like brain, kidney and retina. CRB2 has a ubiquitous expression and has been detected in embryonic brain tissue; but currently there is no data regarding its localization in the adult brain. In our study, we characterized the presence of CRB2 in adult mice brain, where it is particularly enriched in cortex, hippocampus, hypothalamus and cerebellum. Double immunofluorescence analysis confirmed that CRB2 is a neuron-specific protein, present in both soma and projections where colocalizes with certain populations of exocytic and endocytic vesicles and with other members of the Crumbs complex. Finally, in the cortex of CRB1rd8 mutant mice that contain a mutation in the Crb1 gene generating a truncated CRB1 protein, there is an abnormal increase in the expression levels of the CRB2 protein which suggests a possible compensatory mechanism for the malfunction of CRB1 in this mutant background.

Does heart failure therapy differ according to patient sex?

OBJECTIVES: To assess differences in clinical characteristics, treatment and outcome between men and women with heart failure (HF) treated at a multidisciplinary HF unit. All patients had their first unit visit between August 2001 and April 2004. PATIENTS: We studied 350 patients, 256 men, with a mean age of 65 +/- 10.6 years. In order to assess the pharmacological intervention more homogeneously, the analysis was made at one year of follow-up. RESULTS: Women were significantly older than men (69 +/- 8.8 years vs. 63.6 +/- 10.9 years, p < 0.001). Significant differences were found in the HF etiology and in co-morbidities. A higher proportion of men were treated with ACEI (83% vs. 68%, p < 0.001) while more women received ARB (18% vs. 8%, p = 0.006), resulting in a similar percentage of patients receiving either of these two drugs (men 91% vs. women 87%). No significant differences were observed in the percentage of patients receiving beta-blockers, loop diuretics, spironolactone, anticoagulants, amiodarone, nitrates or statins. More women received digoxin (39% vs. 22%, p = 0.001) and more men aspirin (41% vs. 31%, p = 0.004). Carvedilol doses were higher in men (29.4 +/- 18.6 vs. 23.8 +/- 16.4, p = 0.03), ACEI doses were similar between sexes, and furosemide doses were higher in women (66 mg +/- 26.2 vs. 56 mg +/- 26.2, p < 0.05). Mortality at 1 year after treatment analysis was similar between sexes (10.4% men vs. 10.5% women). CONCLUSIONS: Despite significant differences in age, etiology and co-morbidities, differences in treatment between men and women treated at a multidisciplinary HF unit were small. Mortality at 1 year after treatment analysis was similar for both sexes.

[Left atrium diameter: a simple echocardiographic parameter with high prognostic value in heart failure]. / Diámetro de la aurícula izquierda: un parámetro ecocardiográfico sencillo con importante significado pronóstico en la insuficiencia cardíaca.

BACKGROUND AND OBJECTIVE: Left atrium diameter (LAD) is a very simple and easy parameter to obtain by echocardiography. It is influenced by systolic and diastolic ventricular dysfunction and by the coexistence of mitral regurgitation. We evaluated LAD as a predictor of prognosis (2 year mortality) in a heart failure (HF) population admitted to an outpatient HF unit. We compared LAD (mm/m2) with other echocardiographic parameters (left ventricular ejection fraction, left ventricular end-diastolic and end-systolic diameters [mm/m2], mitral regurgitation, degree of diastolic dysfunction and pulmonary artery pressure). PATIENTS AND METHOD: We studied 368 patients (73% men; mean age [standard deviation]: 65.2 [11] years; 60% of ischemic etiology). The mean left ventricular ejection fraction by echocardiography was 32.3% (13.1%). The majority of patients were in NYHA (New York Heart Association) class II (48%) or III (43%). RESULTS: Two years mortality was 20.6%. In the univariate analysis LAD (p < 0.001), left ventricular end-diastolic diameter (p < 0.001), left ventricular end-systolic diameter (p = 0.003), the degree of mitral regurgitation (p = 0.002) and the pattern of diastolic dysfunction (p = 0.004) showed a significant relationship with 2 years mortality, but not left ventricular ejection fraction and pulmonary pressure. In the echocardiographic multivariate analysis, only LAD remained significantly associated with mortality. In the multivariate analysis including important clinical parameters such as age, sex, etiology, time lapsed since symptoms onset, NYHA functional class, and the presence of diabetes, hypertension and atrial fibrillation, LAD remained as independent predictor of 2 years mortality. Patients with LAD less than 25 mm/m2 have a 10.9% mortality, whereas those with LAD equal or greater than 25 mm/m2 have a 30.1% mortality (p < 0.001). CONCLUSIONS: LAD was a good predictor of 2 years mortality, better than other echocardiographic parameters in patients of our outpatient HF unit and was independent of strong clinical parameters.

[Clinical, echocardiographic and prognostic evaluation of atrial fibrillation in patients with heart failure]. / Valoración clínica, ecocardiográfica y pronóstica de la fibrilación auricular en pacientes con insuficiencia cardíaca.

BACKGROUND AND OBJECTIVE: We aimed to assess the prevalence of atrial fibrillation (AF) in a general heart failure (HF) population admitted to a HF unit, analyze the parameters associated with AF, and evaluate its prognostic significance. PATIENTS AND METHOD: 389 patients, 64 with AF at the first visit. Mean (SD) age was 65.38 (10.77) years and 72.5% were men. The main etiology was ischemic heart disease (59.9%). Mean ejection fraction (EF) was 32.25% (13%). Vital status at 2 years was available in 377 patients (97%), 314 in sinus rhythm (SR) and 63 in AF. RESULTS: The prevalence of AF was 15.8%. AF was associated with: older age, female gender, valvular and hypertensive etiology, longer time since the onset of HF symptoms, higher EF, higher left atrium diameter, degree of mitral regurgitation, and lower quality of life, but not with the NYHA functional class. The 2-years mortality (16.7%) was significantly higher in patients with AF (33.3% vs 18.4%; OR = 2.20; 95% confidence interval, 1.21-4). However, when adjusted for other relevant variables such as age, NYHA functional class, ejection fraction, sex and etiology, AF did not remain as an independent prognostic factor. The strongest mortality differences between patients with AF and those with SR where observed in ischemic heart disease and dilated cardiomyopathy. CONCLUSIONS: AF was associated mainly with age, valvular and hypertensive etiology, higher left atrium diameter and lower end-systolic left ventricular diameter. Two years mortality was significantly higher in patients with AF, although other parameters such as age and NYHA functional class had a higher prognostic value.