Large-scale distribution of tuna species in a warming ocean.

Tuna are globally distributed species of major commercial importance and some tuna species are a major source of protein in many countries. Tuna are characterized by dynamic distribution patterns that respond to climate variability and long-term change. Here, we investigated the effect of environmental conditions on the worldwide distribution and relative abundance of six tuna species between 1958 and 2004 and estimated the expected end-of-the-century changes based on a high-greenhouse gas concentration scenario (RCP8.5). We created species distribution models using a long-term Japanese longline fishery dataset and two-step generalized additive models. Over the historical period, suitable habitats shifted poleward for 20 out of 22 tuna stocks, based on their gravity centre (GC) and/or one of their distribution limits. On average, tuna habitat distribution limits have shifted poleward 6.5 km per decade in the northern hemisphere and 5.5 km per decade in the southern hemisphere. Larger tuna distribution shifts and changes in abundance are expected in the future, especially by the end-of-the-century (2080-2099). Temperate tunas (albacore, Atlantic bluefin, and southern bluefin) and the tropical bigeye tuna are expected to decline in the tropics and shift poleward. In contrast, skipjack and yellowfin tunas are projected to become more abundant in tropical areas as well as in most coastal countries' exclusive economic zones (EEZ). These results provide global information on the potential effects of climate change in tuna populations and can assist countries seeking to minimize these effects via adaptive management.

Efecto a largo plazo del tratamiento con presión positiva continua de la vía aérea sobre la arteriosclerosis subclínica en el síndrome de apnea-hipopnea durante el sueño / Long-term effects of continuous positive airway pressure treatment on subclinical atherosclerosis in obstructive sleep apnoea syndrome

Antecedentes y objetivo: El síndrome de apnea-hipopnea durante el sueño (SAHS) es un factor de riesgo de arteriosclerosis. Nuestro objetivo fue evaluar la arteriosclerosis subclínica en los pacientes con SAHS y el efecto del tratamiento con continuous positive airway pressure (CPAP, «presión positiva continua de la vía aérea superior») sobre el grosor íntima-media carotídeo (GIMc). Pacientes y método: Se incluyeron 125 pacientes con sospecha de SAHS. Después de la polisomnografía, 107 pacientes fueron diagnosticados de SAHS; 58 cumplían criterios de tratamiento con CPAP. El GIMc se midió mediante ecografía a nivel basal y a los 2 años de seguimiento en 50 pacientes con SAHS en tratamiento con CPAP y 35 SAHS sin criterio de CPAP. Resultados: Los valores del GIMc fueron superiores en los pacientes con SAHS respecto a los que no tenían SAHS (665 ± 120 frente a 581 ± 78 μm, p = 0,005), sin asociarse con su nivel de gravedad. La presencia de placas de ateroma fue más prevalente en los SAHS que en los no SAHS (48 frente a 2%, p = 0,004). En los pacientes con SAHS, la media del GIMc permaneció estable durante el seguimiento en el grupo sin CPAP, y en el grupo tratado con CPAP disminuyó significativamente (679 ± 122 frente a 631 ± 117 μm, p < 0,0001). Conclusiones: Los pacientes con SAHS presentan un mayor grado de arteriosclerosis subclínica y no se asocia con su gravedad. La ecografía carotídea en el SAHS es un marcador fiable de arteriosclerosis. El tratamiento con CPAP en el SAHS disminuye el GIMc y el riesgo cardiovascular (AU)

Background and objective: Obstructive sleep apnoea (OSA) is associated with an increased risk of cardiovascular disease. Our objective was to evaluate subclinical atherosclerosis in OSA patients and the effect of continuous positive airway pressure (CPAP) treatment on carotid intima-media thickness (cIMT). Patients and method: We included 125 patients with suspected OSA. After polysomnography, 107 patients were diagnosed with OSA; 58 of these met the criteria for CPAP treatment. cIMT was measured by ultrasonography at baseline in all patients and after 2 years of follow up in 50 patients on CPAP and 35 without CPAP treatment. ResultsThe average cIMT was significantly thicker in OSA than in non-OSA patients (665 ± 120 vs. 581 ± 78 μm, P = .005) and did not differ according to OSA severity. Atheromatous carotid plaque was more prevalent in OSA than non-OSA patients (48 vs. 2%, P = .004). Among OSA patients, the mean cIMT remained stable over time in the group without CPAP, whereas cIMT decreased markedly in the CPAP group (679 ± 122 vs. 631 ± 117 μm, P < .0001). Conclusions: Increased cIMT was associated with presence of OSA, but not with its severity. Carotid ultrasound in OSA is a reliable marker of atherosclerosis. CPAP treatment with CPAP in OSA reduces cIMT and cardiovascular risk (AU)

Redistribución de grasa intraabdominal en el tratamiento a largo plazo con presión positiva continua de la vía aérea en los pacientes con síndrome de apnea-hipopnea durante el sueño / Intraabdominal fat redistribution in long-term continuous positive airway pressure treatment in obstructive sleep apnea patients

Fundamento y objetivo: La obesidad es el principal factor de riesgo del síndrome de apneas-hipopneas del sueño (SAHS). El objetivo es evaluar el efecto de la continuous positive airway pressure (CPAP, «presión positiva continua de la vía aérea» a largo plazo en pacientes con SAHS sobre la grasa intraabdominal. Pacientes y métodos: Se incluyeron 50 pacientes SAHS con criterio de CPAP y 35 SAHS no candidatos a CPAP con un seguimiento de 2 años. El visceral adipose tissue (VAT, «tejido adiposo visceral»), el subcutaneous adipose tissue (SAT, «tejido adiposo subcutáneo») y la preaortic intraabdominal fat (PIF, «grasa intraabdominal preaórtica») se midieron mediante ecografía. Resultados: En el grupo SAHS no candidatos a CPAP, la media del SAT y del VAT no cambió durante el seguimiento, pero se observó un aumento del PIF (55,19 [23,44] frente a 63,45 [23,94] mm, p = 0,021). En los pacientes SAHS tratados con CPAP, la media del VAT y del PIF no se modificó, pero el SAT disminuyó a los 2 años del tratamiento con CPAP (11,29 [5,69] frente a 10,47 [5,71] mm, p = 0,012). Conclusiones: El tratamiento con CPAP a largo plazo en los pacientes SAHS produce una redistribución de la grasa intraabdominal y se asocia a un perfil antropométrico de menor riesgo cardiovascular (AU)

Background and objective: Obesity is the main risk factor for obstructive sleep apnoea (OSA). The aim was to evaluate the long-term effect of continuous positive airway pressure (CPAP) on intraabdominal fat distribution in OSA patients. Patients and methods: Fifty OSA patients with and 35 without CPAP treatment criteria were followed-up for 2 years. Visceral and subcutaneous adipose tissue (VAT and SAT) and preaortic intraabdominal fat (PIF) were assessed by sonography. Results: In the non CPAP treated group, SAT and VAT mean values didn’t change, while a significantly PIF growth was observed (55.19 [23.44] vs. 63.45 [23.94] mm, P = .021). In the CPAP treated group, VAT and PIF mean were not changed, while SAT decreased significantly (11.29 [5.69] vs. 10.47 [5.71] mm, P = .012). Conclusions: Long-term CPAP treatment produces intraabdominal fat redistribution and is associated with an anthropometric profile of lower cardiovascular risk in OSA patients (AU)

[Long-term effects of continuous positive airway pressure treatment on subclinical atherosclerosis in obstructive sleep apnoea syndrome]. / Efecto a largo plazo del tratamiento con presión positiva continua de la vía aérea sobre la arteriosclerosis subclínica en el síndrome de apnea-hipopnea durante el sueño.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) is associated with an increased risk of cardiovascular disease. Our objective was to evaluate subclinical atherosclerosis in OSA patients and the effect of continuous positive airway pressure (CPAP) treatment on carotid intima-media thickness (cIMT). PATIENTS AND METHOD: We included 125 patients with suspected OSA. After polysomnography, 107 patients were diagnosed with OSA; 58 of these met the criteria for CPAP treatment. cIMT was measured by ultrasonography at baseline in all patients and after 2 years of follow up in 50 patients on CPAP and 35 without CPAP treatment. RESULTS: The average cIMT was significantly thicker in OSA than in non-OSA patients (665±120 vs. 581±78µm, P=.005) and did not differ according to OSA severity. Atheromatous carotid plaque was more prevalent in OSA than non-OSA patients (48 vs. 2%, P=.004). Among OSA patients, the mean cIMT remained stable over time in the group without CPAP, whereas cIMT decreased markedly in the CPAP group (679±122 vs. 631±117µm, P<.0001). CONCLUSIONS: Increased cIMT was associated with presence of OSA, but not with its severity. Carotid ultrasound in OSA is a reliable marker of atherosclerosis. CPAP treatment with CPAP in OSA reduces cIMT and cardiovascular risk.

Circulating PCSK9 in patients with type 2 diabetes and related metabolic disorders / Concentraciones circulantes de PCSK9 en población con diabetes tipo 2 y alteraciones metabólicas asociadas

Background: PCSK9 is a pivotal molecule in the regulation of lipid metabolism. Previous studies have suggested that PCSK9 expression and its function in LDL receptor regulation could be altered in the context of diabetes. The aim was to assess PCSK9 plasma levels in patients with type 2 diabetes (T2DM) and other related metabolic disorders as well as its relation to the metabolomic profile generated by nuclear magnetic resonance (NMR) and glucose homeostasis. Methods: There were recruited a total of 457 patients suffering from T2DM and other metabolic disorders (metabolic syndrome (MetS), obesity and atherogenic dyslipidaemia (AD) and other disorders). Anamnesis, anthropometry and physical examinations were conducted, and vascular and abdominal adiposity imaging were carried out. Biochemical studies were performed to determine PCSK9 plasma levels 6 weeks after lipid lowering drug wash-out in treated patients. A complete metabolomic lipid profile was also generated by NMR. The rs505151 and rs11591147 genetic variants of PCSK9 gene were identified in patients. Results: The results showed that PCSK9 levels are increased in patients with T2DM and MetS (14% and 13%;p < 0.005, respectively). Circulating PCSK9 levels were correlated with an atherogenic lipid profile and with insulin resistance parameters. PCSK9 levels were also positively associated with AD, as defined by lipoprotein particle number and size. The rs11591147 genetic variant resulted in lower levels of circulating PCSK9 and LDL cholesterol (LDL-C). Conclusions: PCSK9 plasma levels are increased in T2DM and MetS patients and are associated with LDL-C and other parameters of AD and glucose metabolism

Introducción: PCSK9 es una molécula clave en la regulación del metabolismo lipídico. Estudios previos sugieren que la expresión y función de PCSK9 entorno a la regulación del receptor LDL puede alterarse en la diabetes. El objetivo del estudio fue determinar los niveles circulantes de PCSK9 en pacientes con diabetes tipo 2 (DM) y otras enfermedades metabólicas y su relación con las lipoproteínas estudiadas mediante resonancia magnética nuclear (RMN) y la homeostasis de la glucosa. Métodos: Se estudiaron un total de 457 pacientes, afectos de DM y otras alteraciones metabólicas (síndrome metabólico [SMet], obesidad y dislipidemia aterogénica [DA] y otros). Se realizó anamnesis, antropometría, exploración física y estudio vascular de carótidas y adiposidad abdominal. Se realizó bioquímica incluyendo PCSK9 circulante (tras 6 semanas de lavado en pacientes con hipolipemiantes). Se estudió mediante RMN el perfil de lipoproteínas. Se determinaron las variantes genéticas rs505151 y rs11591147 del gen PCSK9. Resultados: Los niveles circulantes de PCSK9 están aumentados en pacientes con DM y SMet (14 y 13%; p<0.005, respectivamente). Los niveles circulantes de PCSK9 se correlacionaron de forma positiva con el perfil lipídico aterogénico y parámetros de resistencia insulínica. Los niveles circulantes de PCSK9 también se asociaron positivamente a DA, definida mediante el número y el tamaño de lipoproteínas analizado mediante RMN. Los portadores de la variante genética rs11591147 mostraron niveles inferiores de PCSK9 plasmática y cLDL. Conclusiones: Los niveles circulantes de PCSK9 están aumentados en pacientes con DM y SMet junto con parámetros de DA y metabolismo de la glucosa, más allá del cLDL

[Intraabdominal fat redistribution in long-term continuous positive airway pressure treatment in obstructive sleep apnea patients]. / Redistribución de grasa intraabdominal en el tratamiento a largo plazo con presión positiva continua de la vía aérea en los pacientes con síndrome de apnea-hipopnea durante el sueño.

BACKGROUND AND OBJECTIVE: Obesity is the main risk factor for obstructive sleep apnoea (OSA). The aim was to evaluate the long-term effect of continuous positive airway pressure (CPAP) on intraabdominal fat distribution in OSA patients. PATIENTS AND METHODS: Fifty OSA patients with and 35 without CPAP treatment criteria were followed-up for 2 years. Visceral and subcutaneous adipose tissue (VAT and SAT) and preaortic intraabdominal fat (PIF) were assessed by sonography. RESULTS: In the non CPAP treated group, SAT and VAT mean values didn't change, while a significantly PIF growth was observed (55.19 [23.44] vs. 63.45 [23.94] mm, P=.021). In the CPAP treated group, VAT and PIF mean were not changed, while SAT decreased significantly (11.29 [5.69] vs. 10.47 [5.71] mm, P=.012). CONCLUSIONS: Long-term CPAP treatment produces intraabdominal fat redistribution and is associated with an anthropometric profile of lower cardiovascular risk in OSA patients.

Circulating PCSK9 in patients with type 2 diabetes and related metabolic disorders.

BACKGROUND: PCSK9 is a pivotal molecule in the regulation of lipid metabolism. Previous studies have suggested that PCSK9 expression and its function in LDL receptor regulation could be altered in the context of diabetes. The aim was to assess PCSK9 plasma levels in patients with type 2 diabetes (T2DM) and other related metabolic disorders as well as its relation to the metabolomic profile generated by nuclear magnetic resonance (NMR) and glucose homeostasis. METHODS: There were recruited a total of 457 patients suffering from T2DM and other metabolic disorders (metabolic syndrome (MetS), obesity and atherogenic dyslipidaemia (AD) and other disorders). Anamnesis, anthropometry and physical examinations were conducted, and vascular and abdominal adiposity imaging were carried out. Biochemical studies were performed to determine PCSK9 plasma levels 6 weeks after lipid lowering drug wash-out in treated patients. A complete metabolomic lipid profile was also generated by NMR. The rs505151 and rs11591147 genetic variants of PCSK9 gene were identified in patients. RESULTS: The results showed that PCSK9 levels are increased in patients with T2DM and MetS (14% and 13%; p<0.005, respectively). Circulating PCSK9 levels were correlated with an atherogenic lipid profile and with insulin resistance parameters. PCSK9 levels were also positively associated with AD, as defined by lipoprotein particle number and size. The rs11591147 genetic variant resulted in lower levels of circulating PCSK9 and LDL cholesterol (LDL-C). CONCLUSIONS: PCSK9 plasma levels are increased in T2DM and MetS patients and are associated with LDL-C and other parameters of AD and glucose metabolism.

Terrestrial and marine perspectives on modeling organic matter degradation pathways.

Organic matter (OM) plays a major role in both terrestrial and oceanic biogeochemical cycles. The amount of carbon stored in these systems is far greater than that of carbon dioxide (CO2 ) in the atmosphere, and annual fluxes of CO2 from these pools to the atmosphere exceed those from fossil fuel combustion. Understanding the processes that determine the fate of detrital material is important for predicting the effects that climate change will have on feedbacks to the global carbon cycle. However, Earth System Models (ESMs) typically utilize very simple formulations of processes affecting the mineralization and storage of detrital OM. Recent changes in our view of the nature of this material and the factors controlling its transformation have yet to find their way into models. In this review, we highlight the current understanding of the role and cycling of detrital OM in terrestrial and marine systems and examine how this pool of material is represented in ESMs. We include a discussion of the different mineralization pathways available as organic matter moves from soils, through inland waters to coastal systems and ultimately into open ocean environments. We argue that there is strong commonality between aspects of OM transformation in both terrestrial and marine systems and that our respective scientific communities would benefit from closer collaboration.

Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess.

Hyperinsulinaemic androgen excess (HIAE) in prepubertal and pubertal girls usually precedes a broader pathological phenotype in adulthood that is associated with anovulatory infertility, metabolic syndrome and type 2 diabetes. The metabolic derangements that determine these long-term health risks remain to be clarified. Here we use NMR and MS-based metabolomics to show that serum levels of methionine sulfoxide in HIAE girls are an indicator of the degree of oxidation of methionine-148 residue in apolipoprotein-A1. Oxidation of apo-A1 in methionine-148, in turn, leads to an impaired maturation of high-density lipoproteins (HDL) that is reflected in a decline of large HDL particles. Notably, such metabolic alterations occur in the absence of impaired glucose tolerance, hyperglycemia and hypertriglyceridemia, and were partially restored after 18 months of treatment with a low-dose combination of pioglitazone, metformin and flutamide.

Circulating PCSK9 levels are positively correlated with NMR-assessed atherogenic dyslipidaemia in patients with high cardiovascular risk.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene regulates cholesterol homoeostasis by accelerating low-density lipoprotein receptor (LDLR) degradation resulting in the decreased catabolism of low-density lipoprotein (LDL) leading to hypercholesterolaemia. PCSK9 has also been related to other metabolic risk factors such as triglycerides (TGs) and glucose levels and body mass index (BMI). Therefore, our aim was to study the relationship between the PCSK9 and the lipid and lipoprotein profile. We studied 267 diabetic and metabolic syndrome patients who were not receiving any lipid-lowering therapy. We measured circulating lipids, cholesterol in remnant lipoproteins (RLPc) and PCSK9 levels. A detailed lipoprotein profile was determined based on NMR. Plasma PCSK9 levels were significantly and positively correlated with TG (r=0.136, P=0.033), total cholesterol (r=0.219, P<0.001) and apoB (apolipoprotein B; r=0.226, P=0.006) circulating levels and with an atherogenic profile of lipoprotein subclasses. In further detail, circulating PCSK9 levels were positively correlated with large very-low density lipoprotein (VLDL) particles, (r=0.210, P=0.001) and with their remnants, the intermediate-density lipoprotein (IDL) particles (r=0.206, P=0.001); positively correlated with smaller LDL particles (for small LDL: r=0.224, P<0.001; for medium small LDL: r=0.235, P<0.001; and for very small LDL: r=0.220, P<0.001); and with high-density lipoprotein (HDL) particles (r=0.146, P<0.001), which is mainly explained by the PCSK9 correlation with the smallest HDL particles (r=0.130, P=0.037). In addition, circulating PCSK9 levels were positively correlated with the pro-atherogenic circulating RLPc levels (r=0.171, P=0.006). All of the correlations were adjusted by age, gender and BMI. PCSK9 levels are significantly and positively correlated with atherogenic lipoproteins such as large VLDL, IDL, the smallest LDL, the smallest HDL particles and RLPc levels.

Interacción de FABP4 con proteínas de membrana de células endoteliales / Interaction of FABP4 with plasma membrane proteins of endothelial cells

Introducción: Fatty acid-binding protein 4 (FABP4) es una adipocina secretada por el tejido adiposo implicada en la regulación del metabolismo energético y la inflamación. FABP4 circulante se asocia con obesidad, dislipidemia aterogénica y síndrome metabólico. Estudios recientes muestran una asociación entre FABP4 circulante y disfunción endotelial, aunque se desconoce cómo se produce esta. El objetivo de este trabajo es estudiar la interacción entre FABP4 con las proteínas de la membrana citoplasmática en células endoteliales. Metodología: Se incubaron células HUVEC con y sin FABP4 (100 ng/ml) durante 5 min. La inmunolocalización de FABP4 se estudió mediante microscopia confocal. Para estudiar las interacciones de FABP4 con las proteínas de membrana de las células HUVEC se diseñó una estrategia que combina incubaciones con o sin 6XHistidine-tag FABP4 (FABP4-His) (100 ng/ml), cross-linking con formaldehído, extracción de proteínas de membrana y western blot. Resultados: Los resultados muestran que FABP4 colocaliza con CD31, una proteína utilizada como marcador de membrana citoplasmática. Además se observan diferentes patrones de western blot en función de la incubación con o sin FABP4-His. El inmunoblot revela la existencia de 3 complejos proteicos de aproximadamente 108, 77 y 33 kDa formados por FABP4 exógena y su posible receptor/es. Discusión: Los resultados obtenidos apoyan la existencia de un complejo proteico capaz de unir FABP4 a las células endoteliales mediante una unión específica. Además, nos permiten avanzar en el conocimiento de los efectos moleculares de FABP4 y, en caso de confirmarse, podrían utilizarse como diana terapéutica para prevenir enfermedades cardiovasculares

Introduction: Fatty acid binding protein (FABP4) is an adipose tissue-secreted adipokine implicated in the regulation of the energetic metabolism and inflammation. High levels of circulating FABP4 have been described in people with obesity, atherogenic dyslipidemia, diabetes and metabolic syndrome. Recent studies have demonstrated that FABP4 could have a direct effect on peripheral tissues and, specifically, on vascular function. It is still unknown how the interaction between FABP4 and the endothelial cells is produced to prompt these effects on vascular function. The objective of this work is studying the interaction between FABP4 and the plasma membrane proteins of endothelial cells. Methodology: HUVEC cells were incubated with and without FABP4 (100 ng/ml) for 5 minutes. Immunolocalization of FABP4 was studied by confocal microscopy. The results showed that FABP4 colocalizates with CD31, a membrane protein marker. A strategy which combines 6XHistidine-tag FABP4 (FABP4-His), incubations with or without FABP4-His (100 ng/ml), formaldehyde cross-linking, cellular membrane protein extraction and western blot, was designed to study the FABP4 interactions with membrane proteins of HUVECs. Results: The results showed different western blot profiles depending of the incubation with or without FABP4-His. The immunoblot revelead three covalent protein complexes of about 108, 77 and 33 kDa containing FAPB4 and its putative receptor. Discussion: The existence of a specific binding protein complex able to bind FABP4 to endothelial cells is supported by these results. The obtained results will permit us advance in the molecular knowledge of FABP4 effects as well as use this protein and its receptor as therapeutic target to prevent cardiovascular

[Interaction of FABP4 with plasma membrane proteins of endothelial cells]. / Interacción de FABP4 con proteínas de membrana de células endoteliales.

INTRODUCTION: Fatty acid binding protein (FABP4) is an adipose tissue-secreted adipokine implicated in the regulation of the energetic metabolism and inflammation. High levels of circulating FABP4 have been described in people with obesity, atherogenic dyslipidemia, diabetes and metabolic syndrome. Recent studies have demonstrated that FABP4 could have a direct effect on peripheral tissues and, specifically, on vascular function. It is still unknown how the interaction between FABP4 and the endothelial cells is produced to prompt these effects on vascular function. The objective of this work is studying the interaction between FABP4 and the plasma membrane proteins of endothelial cells. METHODOLOGY: HUVEC cells were incubated with and without FABP4 (100 ng/ml) for 5 minutes. Immunolocalization of FABP4 was studied by confocal microscopy. The results showed that FABP4 colocalizates with CD31, a membrane protein marker. A strategy which combines 6XHistidine-tag FABP4 (FABP4-His), incubations with or without FABP4-His (100 ng/ml), formaldehyde cross-linking, cellular membrane protein extraction and western blot, was designed to study the FABP4 interactions with membrane proteins of HUVECs. RESULTS: The results showed different western blot profiles depending of the incubation with or without FABP4-His. The immunoblot revelead three covalent protein complexes of about 108, 77 and 33 kDa containing FAPB4 and its putative receptor. DISCUSSION: The existence of a specific binding protein complex able to bind FABP4 to endothelial cells is supported by these results. The obtained results will permit us advance in the molecular knowledge of FABP4 effects as well as use this protein and its receptor as therapeutic target to prevent cardiovascular.

Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients.

HDL-increasing drugs such as fenofibrate and niacin have failed to decrease the cardiovascular risk in patients with type 2 diabetes. Drug-mediated quantitative and qualitative HDL modifications could be involved in these negative results. To evaluate the quantitative and qualitative effects of niacin and fenofibrate on HDL in patients with type 2 diabetes, a prospective, randomised controlled intervention trial was conducted. Thirty type 2 diabetic patients with low HDL were randomised to receive either fenofibrate (FFB) or niacin + laropiprant (ERN/LPR) as an add-on to simvastatin treatment for 12 weeks according to a crossover design. At the basal point and after each intervention period, physical examinations and comprehensive standard biochemical determinations and HDL metabolomics were performed. Thirty nondiabetic patients with normal HDL were used as a basal control group. ERN/LRP, but not FFB, significantly increased HDL cholesterol. Neither ERN/LRP nor FFB reversed the HDL particle size or particle number to normal. ERN/LRP increased apoA-I but not apoA-II, whereas FFB produced the opposite effect. FFB significantly increased Preß1-HDL, whereas ERN/LRP tended to lower Preß1-HDL. CETP and LCAT activities were significantly decreased only by ERN/LRP. PAF-AH activity in HDL and plasma decreased with the use of both agents. Despite their different actions on antioxidant parameters, none of the treatments induced detectable antioxidant improvements. ERN/LRP and FFB had strikingly different effects on HDL quantity and quality, as well as on HDL cholesterol concentrations. When prescribing HDL cholesterol increasing drugs, this differential action should be considered.

Prevalence of atherogenic dyslipidemia in primary care patients at moderate-very high risk of cardiovascular disease. Cardiovascular risk perception

Introduction: Atherogenic dyslipidemia is an important risk factor for cardiovascular disease. We aim to determine atherogenic dyslipidemia prevalence in primary care patients at moderate-very high cardiovascular risk and its associated cardiovascular risk perception in Spain. Methods: This cross-sectional study included 1137 primary care patients. Patients had previous cardiovascular disease, diabetes mellitus, SCORE risk ≥ 3, severe hypertension or dyslipidemia. Atherogenic dyslipidemia was defined as low HDL-C (< 40 mg/dL [males], < 50 mg/dL [females]) and elevated triglycerides (≥ 1 50 mg/dL). A visual analog scale was used to define a perceived cardiovascular disease risk score. Results: Mean age was 63.9 ± 9.7 years (64.6% males). The mean BMI was 29.1 ± 4.3 kg/m2, and mean waist circumference 104.2 ± 12.7 cm (males), and 97.2 ± 14.0 cm (females). 29.4% were smokers, 76.4% had hypertension, 48.0% were diabetics, 24.7% had previous myocardial infarction, and 17.8% peripheral arterial disease. European guidelines classified 83.6% at very high cardiovascular risk. Recommended HDL-C levels were achieved by 50.1% of patients and 37.3% had triglycerides in the reference range. Target LDL-C was achieved by 8.8%. The overall atherogenic dyslipidemia prevalence was 27.1% (34.1% in diabetics). This prevalence in patients achieving target LDL-C was 21.4%. Cardiovascular risk perceived by patients was 4.3/10, while primary care physicians scored 5.7/10. Conclusions: When LDL-C levels are controlled, atherogenic dyslipidemia is more prevalent in those patients at highest cardiovascular risk and with diabetes. This highlights the importance of intervention strategies to prevent the residual vascular risk in this population. Both patients and physicians underestimated cardiovascular risk

Introducción: La dislipidemia aterogénica representa un factor de riesgo importante de enfermedad cardiovascular. Se pretende determinar la prevalencia de dislipidemia aterogénica en pacientes de atención primaria con riesgo cardiovascular de moderado a muy alto y la percepción de riesgo cardiovascular asociado en España. Métodos: Estudio transversal que incluyó 1.137 pacientes de atención primaria. Los pacientes presentaban enfermedad cardiovascular previa, diabetes mellitus, SCORE ≥ 3, hipertensión arterial severa o dislipidemia. La dislipidemia aterogénica se definió como C-HDL bajo (< 40 mg/dl [hombres], < 50 mg/dl [mujeres]) y triglicéridos elevados (≥ 150 mg/dl). Para definir la puntuación de percepción de riesgo de enfermedad cardiovascular se utilizó una escala visual analógica. Resultados: La edad media fue de 63,9 ± 9,7 años (64,6% hombres). El IMC promedio fue de 29,1 ± 4,3 kg/m2, y la media del perímetro de la cintura de 104,2 ± 12,7cm (hombres) y 97,2 ± 14,0 cm (mujeres); el 29,4% eran fumadores, el 76,4% hipertensos, el 48,0% diabéticos, el 24,7% tenían antecedentes de infarto de miocardio y el 17,8% enfermedad arterial periférica. El 83,6% se clasificaron como pacientes de muy alto riesgo cardiovascular según las guías europeas. El 50,1% de los pacientes alcanzaron los niveles recomendados de C-HDL y el 37,3% tenían los triglicéridos dentro del rango. El 8,8% consiguieron niveles objetivo de C-LDL. La prevalencia general de dislipidemia aterogénica fue del 27,1% (34,1% en diabéticos). Esta prevalencia en los pacientes que alcanzaron niveles objetivo de C-LDL fue del 21,4%. El riesgo cardiovascular percibido por los pacientes fue de 4,3/10, mientras que sus médicos de atención primaria puntuaron un 5,7/10. Conclusiones: Cuando se controlan los niveles de C-LDL la dislipidemia aterogénica es más prevalente en aquellos pacientes con mayor riesgo cardiovascular y diabéticos, lo que pone de manifiesto la importancia de las estrategias de intervención para prevenir el riesgo vascular residual en esta población. Tanto pacientes como médicos subestimaron el riesgo cardiovascular

Prevalence of atherogenic dyslipidemia in primary care patients at moderate-very high risk of cardiovascular disease. Cardiovascular risk perception.

INTRODUCTION: Atherogenic dyslipidemia is an important risk factor for cardiovascular disease. We aim to determine atherogenic dyslipidemia prevalence in primary care patients at moderate-very high cardiovascular risk and its associated cardiovascular risk perception in Spain. METHODS: This cross-sectional study included 1137 primary care patients. Patients had previous cardiovascular disease, diabetes mellitus, SCORE risk ≥ 3, severe hypertension or dyslipidemia. Atherogenic dyslipidemia was defined as low HDL-C (<40 mg/dL [males], <50 mg/dL [females]) and elevated triglycerides (≥ 150 mg/dL). A visual analog scale was used to define a perceived cardiovascular disease risk score. RESULTS: Mean age was 63.9 ± 9.7 years (64.6% males). The mean BMI was 29.1 ± 4.3 kg/m(2), and mean waist circumference 104.2 ± 12.7 cm (males), and 97.2 ± 14.0 cm (females). 29.4% were smokers, 76.4% had hypertension, 48.0% were diabetics, 24.7% had previous myocardial infarction, and 17.8% peripheral arterial disease. European guidelines classified 83.6% at very high cardiovascular risk. Recommended HDL-C levels were achieved by 50.1% of patients and 37.3% had triglycerides in the reference range. Target LDL-C was achieved by 8.8%. The overall atherogenic dyslipidemia prevalence was 27.1% (34.1% in diabetics). This prevalence in patients achieving target LDL-C was 21.4%. Cardiovascular risk perceived by patients was 4.3/10, while primary care physicians scored 5.7/10. CONCLUSIONS: When LDL-C levels are controlled, atherogenic dyslipidemia is more prevalent in those patients at highest cardiovascular risk and with diabetes. This highlights the importance of intervention strategies to prevent the residual vascular risk in this population. Both patients and physicians underestimated cardiovascular risk.

Circulating FABP4 and FABP5 levels are differently linked to OSA severity and treatment.

OBJECTIVE: To evaluate circulating adipocyte and epidermal fatty acid-binding protein (FABP4 and FABP5) concentrations in patients with obstructive sleep apnea (OSA), as well as the effects of continuous positive airway pressure (CPAP) treatment. METHODS: Our cross-sectional study included 125 patients. After polysomnography, 58 participants met the criteria for CPAP treatment and were included in a closed cohort study of 8 weeks of CPAP treatment. General anthropometric and biochemical data and circulating FABP4 and FABP5 levels were determined in all patients at baseline and after CPAP treatment in those receiving this therapy. RESULTS: Circulating FABP4 but not FABP5 levels were higher in patients with OSA (P = 0.003). FABP4 but not FABP5 values were associated with parameters of OSA severity independently of age, gender, adiposity and insulin resistance (P < 0.05). FABP4 but not FABP5 concentrations were determinants of OSA presence (OR: 1.11, P = 0.010) and severity (OR: 1.06, P = 0.020). After CPAP treatment, FABP4 levels decreased in the more severe patients (P = 0.019), while FABP5 levels increased in all patients (P < 0.001). CONCLUSIONS: FABP4 is directly associated with obstructive sleep apnea severity and did not change with continuous positive airway pressure treatment, while FABP5 was not associated with obstructive sleep apnea severity and increased with continuous positive airway pressure treatment. FABP4 and FABP5 have different associations with obstructive sleep apnea. FABP4 but not FABP5 could be considered a marker of metabolic alterations in obstructive sleep apnea patients.

Akt and ERK/Nrf2 activation by PUFA oxidation-derived aldehydes upregulates FABP4 expression in human macrophages.

OBJECTIVE: In macrophages, adipocyte fatty acid-binding protein (FABP4) coordinates key events in oxidized LDL-induced foam cell formation, such as cholesterol trafficking and inflammatory responses. Nrf2 is a redox-sensitive transcription factor with antioxidant and anti-inflammatory properties. We investigated the involvement of the Nrf2 signaling pathway in FABP4-upregulation in response to aldehydes that are derived from polyunsaturated fatty acid (PUFA) oxidation. METHODS AND RESULTS: Using RT-PCR and western blotting, we found that the aldehyde 2,4-decadienal (2,4-DDE) produced a marked increase in FABP4 mRNA and protein levels. 2,4-DDE acts at the transcriptional level of FABP4 by promoting mRNA synthesis and prolonging the half-life of the de novo synthesized mRNA. 2,4-DDE consistently enhanced nuclear translocation of phosphorylated Nrf2, which was mediated by the activation of the Akt and ERK signaling pathways. A chromatin immunoprecipitation assay showed the in vivo binding of activated Nrf2 to a newly identified ARE site in the human FABP4 promoter. CONCLUSIONS: We propose an Akt and ERK/Nrf2-dependent FABP4 upregulation pathway in response to PUFA oxidation end-products in human macrophages. These results open a new avenue for putative therapeutic targets addressed to control atherogenesis.

Parallel evolution of circulating FABP4 and NT-proBNP in heart failure patients.

BACKGROUND: Circulating adipocyte fatty acid-binding protein (FABP4) levels are considered to be a link between obesity, insulin resistance, diabetes, and cardiovascular (CV) diseases. In vitro, FABP4 has exhibited cardiodepressant activity by suppressing cardiomyocyte contraction. We have explored the relationship between FABP4 and the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) as a clinical parameter of heart failure (HF). METHODS: We included 179 stable HF patients who were referred to a specialized HF unit, 108 of whom were prospectively followed for up to 6 months. A group of 163 non-HF patients attending a CV risk unit was used as the non-HF control group for the FABP4 comparisons. RESULTS: In the HF patients, FABP4 and NT-proBNP were assayed, along with a clinical and functional assessment of the heart at baseline and after 6 months of specialized monitoring. The FABP4 levels were higher in the patients with HF than in the non-HF high CV risk control group (p<0.001). The FABP4 levels were associated with the NT-proBNP levels in patients with HF (r=0.601, p<0.001), and this association was stronger in the diabetic patients. FABP4 was also associated with heart rate and the results of the 6-minute walk test. After the follow-up period, FABP4 decreased in parallel to NT-proBNP and to the clinical parameters of HF. CONCLUSIONS: FABP4 is associated with the clinical manifestations and biomarkers of HF. It exhibits a parallel evolution with the circulating levels of NT-proBNP in HF patients.

Even low physical activity levels improve vascular function in overweight and obese postmenopausal women.

OBJECTIVE: Some individuals with cardiovascular risk are unable to achieve even the lower internationally recommended level of physical activity (PA). We aimed to study the impact of a lower-than-advised level of PA on small artery vascular function and oxidative stress in overweight and obese postmenopausal women. METHODS: Forty-seven overweight and obese postmenopausal women completed a 4-month program of 1-hour low-intensity PA for 2 days per week. Before and after the intervention, PA level (metabolic equivalent tasks/h/wk), endogenous antioxidant status (superoxide dismutase and erythrocyte lysate and glutathione peroxidase erythrocyte lysate concentrations, superoxide dismutase plasma and glutathione peroxidase plasma [GPXa] activities, and oxidized low-density lipoprotein), asymmetrical dimethylarginine concentrations, endothelial function by small artery reactive hyperemia index (saRHI), and resting heart rate (RHR) were assessed. RESULTS: After the intervention, a significant increase in GPXa and decreases in asymmetrical dimethylarginine concentrations and RHR (P < 0.001 for all) were observed. Increases in PA were positively associated with increases in saRHI (r = 0.330, P = 0.027) and GPXa (r = 0.299, P = 0.05) and a decrease in RHR (r = -0.297, P = 0.047). Multivariate analyses showed that the independent predictors of saRHI improvement were an increase in PA (ß = 2.63; 95% CI, 1.24-4.19; P = 0.019), a decrease in RHR (ß = 1.96; 95% CI, 1.01-5.03; P = 0.048), and an increase in GPXa (ß = 2.64; 95% CI, 1.18-5.08; P = 0.021). CONCLUSIONS: Even low-intensity PA improves antioxidant capacity, RHR, and saRHI in postmenopausal women. Advising postmenopausal women to increase their PA at any level seems warranted based on our preliminary and hypothesis-generating data.

Substituting non-HDL cholesterol with LDL as a guide for lipid-lowering therapy increases the number of patients with indication for therapy.

AIM: Our objective was to assess the number of patients with an indication for lipid-lowering therapy according to their non-HDL cholesterol (N-HDL-C) (>130 mg/dL) concentrations despite on-target LDL (≤100 mg/dL) values determined using ultracentrifugation (UC) or direct enzymatic methods (DM). METHODS: In 1590 patients we studied the lipid profile using standard biochemical methods and sequential UC (N = 637) or triglyceride (TG) independent DM (N = 953). The indications for lipid-lowering therapy were compared by evaluating the real LDL concentration or N-HDL-C concentration. RESULTS: The LDL/N-HDL-C correlation significantly decreased with increasing triglyceride concentrations: normal (r = 0.924, p < 0.001), 150-400 mg/dL (r = 0.825, p < 0.001) and higher than 400 mg/dL (r = 0.460, p < 0.001) (p < 0.001). The percentage of patients with an N-HDL-C concentration above the recommended level, despite having an LDL concentration that was on target, also increased significantly across the TG tertiles (3.1%, 15.6% and 57.%, respectively; p < 0.001). Of the patients with a TG level above 400 mg/dL and an LDL concentration that was on target, 86% had an N-HDL-C concentration above 130 mg/dL. Of the patients with a TG level above 400 and an N-HDL-C concentration qualifying for therapy, 40% had an LDL concentration that was on target. The ApoB concentration had a stronger concordance with the LDL concentration than N-HDL-C. CONCLUSIONS: Using the N-HDL-C concentration as a therapeutic target in hypertriglyceridemic patients almost doubled the number of patients requiring treatment. The ApoB concentration had a better association with LDL when determining the need for lipid-lowering therapy.