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Hypertension is the most important risk factor for global disease burden. Detection and management of hypertension are considered as key issues for individual and public health, as adequate control of blood pressure levels markedly reduces morbidity and mortality associated with hypertension. Aims of these practice guidelines for the management of arterial hypertension of the Spanish Society of Hypertension include offering simplified schemes for diagnosis and treatment for daily practice, and strategies for public health promotion. The Spanish Society of Hypertension assumes the 2018 European guidelines for management of arterial hypertension developed by the European Society of Cardiology and the European Society of Hypertension, although relevant aspects of the 2017 American College of Cardiology/American Heart Association guidelines and the 2020 International Society of Hypertension guidelines are also commented. Hypertension is defined as a persistent elevation in office systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg, and assessment of out-of-office blood pressure and global cardiovascular risk are considered of key importance for evaluation and management of hypertensive patients. The target for treated blood pressure should be < 130/80 for most patients. The treatment of hypertension involves lifestyle interventions and drug therapy. Most people with hypertension need more than one antihypertensive drug for adequate control, so initial therapy with two drugs, and single pill combinations are recommended for a wide majority of hypertensive patients., (Copyright © 2022 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Alcohol use disorder (AUD) causes complex alterations in the brain that are poorly understood. The heterogeneity of drinking patterns and the high incidence of comorbid factors compromise mechanistic investigations in AUD patients. Here we used male Marchigian Sardinian alcohol-preferring (msP) rats, a well established animal model of chronic alcohol drinking, and a combination of longitudinal resting-state fMRI and manganese-enhanced MRI to provide objective measurements of brain connectivity and activity, respectively. We found that 1 month of chronic alcohol drinking changed the correlation between resting-state networks. The change was not homogeneous, resulting in the reorganization of pairwise interactions and a shift in the equilibrium of functional connections. We identified two fundamentally different forms of network reorganization. First is functional dedifferentiation, which is defined as a regional increase in neuronal activity and overall correlation, with a concomitant decrease in preferential connectivity between specific networks. Through this mechanism, occipital cortical areas lost their specific interaction with sensory-insular cortex, striatal, and sensorimotor networks. Second is functional narrowing, which is defined as an increase in neuronal activity and preferential connectivity between specific brain networks. Functional narrowing strengthened the interaction between striatal and prefrontocortical networks, involving the anterior insular, cingulate, orbitofrontal, prelimbic, and infralimbic cortices. Importantly, these two types of alterations persisted after alcohol discontinuation, suggesting that dedifferentiation and functional narrowing rendered persistent network states. Our results support the idea that chronic alcohol drinking, albeit at moderate intoxicating levels, induces an allostatic change in the brain functional connectivity that propagates into early abstinence. SIGNIFICANCE STATEMENT Excessive consumption of alcohol is positioned among the top five risk factors for disease and disability. Despite this priority, the transformations that the nervous system undergoes from an alcohol-naive state to a pathologic alcohol drinking are not well understood. In our study, we use an animal model with proven translational validity to study this transformation longitudinally. The results show that shortly after chronic alcohol consumption there is an increase in redundant activity shared by brain structures, and the specific communication shrinks to a set of pathways. This functional dedifferentiation and narrowing are not reversed immediately after alcohol withdrawal but persist during early abstinence. We causally link chronic alcohol drinking with an early and abstinence-persistent retuning of the functional equilibrium of the brain., (Copyright © 2022 the authors.)

Sodium-glucose transport protein 2 (SGLT2) inhibitors are a new class of oral hypoglycemic agents that increase urinary glucose excretion independently of insulin secretion, although an apparently simple mechanism, but with multiple metabolic effects. Dapagliflozin was the first SGLT2 inhibitor marketed in Europe in 2012 for the treatment of patients with type 2 diabetes, and consequently, with the greatest clinical experience. The results of different clinical trials and real-life studies have demonstrated its effectiveness in glycemic control, as they reduce glycosylated hemoglobin, while achieving a decrease in body weight and blood pressure, among others, providing a comprehensive metabolic protection., (Copyright © 2021 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

To substantially reduce the risk of hospitalization and death among subjects with heart failure (HF) and reduced left ventricular ejection fraction, it is necessary to make a comprehensive approach of the different neurohormonal systems that are implied in its etiopathogenesis, including not only sympathetic nervous system, and renin-angiotensin system, but also vasoactive peptides and sodium-glucose transport protein 2. The DAPA-HF trial demonstrated that the addition of dapagliflozin to the standard treatment in HF with reduced left ventricular ejection fraction, markedly decreases the risk of cardiovascular death, HF hospitalization and overall death. In addition, dapagliflozin improves functional class and quality of life. Importantly, the prognostic benefit starts early after initiating treatment with dapagliflozin, regardless baseline therapy or the presence of diabetes. All these evidences make dapagliflozin as one of the mainstays of treatment for the management of HF with reduced left ventricular ejection fraction., (Copyright © 2021 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Despite traditional treatments, morbidity and mortality of patients with heart failure (HF) and reduced left ventricular ejection fraction remains unacceptably high. Traditionally, guidelines recommended a step by step approach in the management of this population. However, this approach could delay the prescription of some drugs with proven efficacy on morbidity and prognosis. As current HF guidelines recommend, an initial comprehensive approach with the aim of targeting all neurohormonal systems that are implied in the etiopathogenesis of HF seems necessary. The DAPA-HF trial demonstrated that dapagliflozin markedly reduces the risk of HF hospitalization, and also improves prognosis. Consequently, dapagliflozin should be considered as a first-line therapy in the management of these patients. On the other hand, primary care physicians are essential for the prevention and treatment of patients with HF and reduced left ventricular ejection fraction. As a result, it is mandatory that they know when and how dapagliflozin should be used. In this review, a practical approach for an appropriate use of this drug is provided., (Copyright © 2021 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Human imaging data suggest that the motivational processes associated with alcohol reward are reflected in the patterns of neural activation after alcohol or alcohol-related cues. In animal models of alcohol drinking, however, the changes in brain activation during voluntary alcohol ingestion are poorly known. In order to improve the translational utility of animal models, we examined alcohol-induced functional brain activation in Alko Alcohol (AA) and Marchigian-Sardinian alcohol-preferring (msP) rats that drink voluntarily high levels of alcohol, but exhibit widely different neurochemical and behavioral traits cosegregated with alcohol preference. Brain imaging was performed using manganese-enhanced MRI (MEMRI), which is based on accumulation of Mn2+ ions in activated neurons, allowing the identification of functional neuronal networks recruited during specific behaviors in awake animals during a subsequent imaging session under anesthesia. MEMRI was performed following 4 weeks of voluntary alcohol drinking, using water drinking as the control. Despite similar levels of alcohol drinking, strikingly different alcohol-induced neuronal activity patterns were observed in AA and msP rats. Overall, functional activation in the AA rats was more widespread, involving large cortical areas and subcortical structures, such as the bed nucleus of the stria terminalis, preoptic area, hypothalamus, periaqueductal grey, and substantia nigra. In the msP rats, however, alcohol-related activation was largely confined to prefrontal cortical regions and insular cortex, and olfactory areas. Overlapping areas of activation found in both rat lines included the nucleus accumbens, prelimbic, orbital, and insular cortex. In conclusion, our data reveal strikingly different brain circuits associated with alcohol drinking in two genetically different rat lines and suggest innately different motivational and behavioral processes driving alcohol drinking. These findings have important implications for the use of these lines in translational alcohol research., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To ascertain the opinion of physicians about diagnostic criteria, control targets, control rates, and therapeutic approach of patients with dyslipidaemia in Spain., Methods: A specific questionnaire was created about diagnostic criteria, control targets, control rates, lipid lowering therapies, and therapeutic inertia in patients with dyslipidaemia. Physicians completed the questionnaire online during a 4-month period., Results: A total of 959 questionnaires were collected from all over Spain. The most frequent scale to stratify cardiovascular risk is SCORE (54.9%), and guidelines from the European Society of Cardiology are the most common guidelines used (50.5%). The majority of patients are on primary prevention (57.7%), and 31.4% have a high-very high cardiovascular risk. More than 70% of investigators considered that the target among patients at very high risk and those in secondary prevention is an LDL cholesterol < 70 mg/dL. It is considered by 60.0% and 66.4% of investigators that their patients on primary and secondary prevention, respectively, achieve control targets. Statins are the most common lipid lowering drugs used, followed by ezetimibe. In the majority of cases, when a patient is not adequately controlled with statins, there is an increase in the dose or a change to another statin. Poor adherence to treatment and therapeutic inertia are the main reasons for poor LDL cholesterol control., Conclusions: The Cardio Right Care CVR Control project allows those aspects to be identified, as well as areas of improvement in patients with dyslipidaemia in Spain., (Copyright © 2020 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Neuroimaging techniques are now widely used to study human cognition. The functional associations between brain areas have become a standard proxy to describe how cognitive processes are distributed across the brain network. Among the many analysis tools available, dynamic models of brain activity have been developed to overcome the limitations of original connectivity measures such as functional connectivity. This goes in line with the many efforts devoted to the assessment of directional interactions between brain areas from the observed neuroimaging activity. This opinion article provides an overview of our model-based whole-brain effective connectivity to analyze fMRI data, while discussing the pros and cons of our approach with respect to other established approaches. Our framework relies on the multivariate Ornstein-Uhlenbeck (MOU) process and is thus referred to as MOU-EC. Once tuned, the model provides a directed connectivity estimate that reflects the dynamical state of BOLD activity, which can be used to explore cognition. We illustrate this approach using two applications on task-evoked fMRI data. First, as a connectivity measure, MOU-EC can be used to extract biomarkers for task-specific brain coordination, understood as the patterns of areas exchanging information. The multivariate nature of connectivity measures raises several challenges for whole-brain analysis, for which machine-learning tools present some advantages over statistical testing. Second, we show how to interpret changes in MOU-EC connections in a collective and model-based manner, bridging with network analysis. Our framework provides a comprehensive set of tools that open exciting perspectives to study distributed cognition, as well as neuropathologies., (© 2019 Massachusetts Institute of Technology.)

T***he current control of low-density lipoprotein cholesterol among patients with atherosclerotic cardiovascular disease is very low and this is associated with an increase of cardiovascular outcomes. In addition, the latter this happens, the risk will be greater. This is mainly due to an insufficient use of the lipid-lowering therapy currently available. In fact, with current treatments (statins, ezetimibe and PCSK9 inhibitors), the majority of patients in secondary prevention should achieve low-density lipoprotein cholesterol goals. For these reasons, in this manuscript promoted by the Spanish Society of Cardiology we propose three simple and feasible decision-making algorithms that include the majority of clinical scenarios among patients with ischemic heart disease, with the double aim of attaining therapeutic goals in the majority of patients as soon as possible; in secondary prevention the magnitude of the benefit is risk- and time-dependent., (Copyright © 2019 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

The current paradigm in the nutrition sciences states that the basic nutritional unit is not the nutrients, but the foods that contain them (oils, nuts, dairy products, eggs, red or processed meats, etc.). These act as a food matrix in which the different nutrients synergistically or antagonistically modulate their effects on the various metabolic pathways determining health and disease. Food is not based on nutrients or isolated foods but on complex mixtures of one and the other that are part of a specific food pattern, a concept that has been targeted as the most pertinent to evaluate the associations between nutrition and health or disease. This document presents a summary of the available evidence on the relationship between different foods and cardiovascular health, and offers simple recommendations to be implemented in the dietary advice offered by the health professional., (Copyright © 2019. Publicado por Elsevier España, S.L.U.)

The current paradigm in the nutrition sciences states that the basic nutritional unit is not the nutrients, but the foods that contain them (oils, nuts, dairy products, eggs, red or processed meats, etc.). These act as a food matrix in which the different nutrients synergistically or antagonistically modulate their effects on the various metabolic pathways determining health and disease. Food is not based on nutrients or isolated foods but on complex mixtures of one and the other that are part of a specific food pattern, a concept that has been targeted as the most pertinent to evaluate the associations between nutrition and health or disease. This document presents a summary of the available evidence on the relationship between different foods and cardiovascular health, and offers simple recommendations to be implemented in the dietary advice offered by the health professional., (Copyright © 2019. Publicado por Elsevier España, S.L.U.)

The study of brain communication based on fMRI data is often limited because such measurements are a mixture of session-to-session variability with subject- and condition-related information. Disentangling these contributions is crucial for real-life applications, in particular when only a few recording sessions are available. The present study aims to define a reliable standard for the extraction of multiple signatures from fMRI data, while verifying that they do not mix information about the different modalities (e.g., subjects and conditions such as tasks performed by them). In particular, condition-specific signatures should not be contaminated by subject-related information, since they aim to generalize over subjects. Practically, signatures correspond to subnetworks of directed interactions between brain regions (typically 100 covering the whole brain) supporting the subject and condition identification for single fMRI sessions. The key for robust prediction is using effective connectivity instead of functional connectivity. Our method demonstrates excellent generalization capabilities for subject identification in two datasets, using only a few sessions per subject as reference. Using another dataset with resting state and movie viewing, we show that the two signatures related to subjects and tasks correspond to distinct subnetworks, which are thus topologically orthogonal. Our results set solid foundations for applications tailored to individual subjects, such as clinical diagnostic., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The objective of this protocol is to know which test are needed to study an anaemia in a patient with chronic kidney disease, the differential diagnosis of renal anaemia, to know and correct other deficiency anaemias, and the criteria for referral to Nephrology or other specialties of the anaemic patient with chronic kidney disease., (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

The objective of this protocol is to know which test are needed to study an anaemia in a patient with chronic kidney disease, the differential diagnosis of renal anaemia, to know and correct other deficiency anaemias, and the criteria for referral to Nephrology or other specialties of the anaemic patient with chronic kidney disease., (Copyright © 2017. Publicado por Elsevier España, S.L.U.)

The objective of this protocol is to know which test are needed to study an anaemia in a patient with chronic kidney disease, the differential diagnosis of renal anaemia, to know and correct other deficiency anaemias, and the criteria for referral to Nephrology or other specialties of the anaemic patient with chronic kidney disease., (Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

In inflammatory disease, the levels of high-density lipoprotein cholesterol (HDL-C) decrease, and the composition of HLD-C changes. Data from the "non-inflammatory" general population indicate the presence of the same phenomenon, albeit to a smaller extent. Levels of uricaemia contribute to the overall inflammatory state of patients. The aim of this study was to analyse the association between inflammatory state, levels of uricaemia, and levels of HLD-C in a hypertensive Spanish population aged 65 or older. This was a retrospective analysis of the FAPRES database. We compared lipid levels [HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides] in terciles of patients according to their leukocyte counts and uricaemia. When we observed statistically significant differences at a 95% confidence level, we constructed a multivariable linear regression model to adjust for possible confounders. We analysed 860 patients (52.7% women) with a mean age of 72.9 years (±5.8). Participants in the highest tercile for leukocytes or uricaemia presented with significantly lower levels of HDL-C and higher levels of triglycerides, but there was no difference in total cholesterol or LDL-C. The multivariable analysis confirmed an independent and inverse association between HDL-C and both leukocytes (β = -0.001, p = 0.025) and uricaemia (β = -1.054, p = 0037) as well as an independent, direct association between triglycerides and both leukocytes (β = 0.004, p = 0.049), and uricaemia (β = 8.411, p = 0.003). In hypertensive adults aged 65 or older, inflammatory state, and uricaemia independently operate to decrease HDL-C-these findings confirm those described in studies in people with inflammatory disease. This phenomenon could help to define a proatherogenic profile in people without inflammatory disease.

The Rubinstein-Taybi Syndrome (RSTS) is a congenital disease that affects brain development causing severe cognitive deficits. In most cases the disease is associated with dominant mutations in the gene encoding the CREB binding protein (CBP). In this work, we present the first quantitative analysis of brain abnormalities in a mouse model of RSTS using magnetic resonance imaging (MRI) and two novel self-developed automated algorithms for image volumetric analysis. Our results quantitatively confirm key syndromic features observed in RSTS patients, such as reductions in brain size (-16.31%, p < 0.05), white matter volume (-16.00%, p < 0.05), and corpus callosum (-12.40%, p < 0.05). Furthermore, they provide new insight into the developmental origin of the disease. By comparing brain tissues in a region by region basis between cbp(+/-) and cbp(+/+) littermates, we found that cbp haploinsufficiency is specifically associated with significant reductions in prosencephalic tissue, such us in the olfactory bulb and neocortex, whereas regions evolved from the embryonic rhombencephalon were spared. Despite the large volume reductions, the proportion between gray-, white-matter and cerebrospinal fluid were conserved, suggesting a role of CBP in brain size regulation. The commonalities with holoprosencephaly and arhinencephaly conditions suggest the inclusion of RSTS in the family of neuronal migration disorders.

Background and Objective: Meaningful targeting of brain structures is required in a number of experimental designs in neuroscience. Current technological developments as high density electrode arrays for parallel electrophysiological recordings and optogenetic tools that allow fine control of activity in specific cell populations provide powerful tools to investigate brain physio-pathology. However, to extract the maximum yield from these fine developments, increased precision, reproducibility and cost-efficiency in experimental procedures is also required., Methods: We introduce here a framework based on magnetic resonance imaging (MRI) and digitized brain atlases to produce customizable 3D-environments for brain navigation. It allows the use of individualized anatomical and/or functional information from multiple MRI modalities to assist experimental neurosurgery planning and in vivo tissue processing., Results: As a proof of concept we show three examples of experimental designs facilitated by the presented framework, with extraordinary applicability in neuroscience., Conclusions: The obtained results illustrate its feasibility for identifying and selecting functionally and/or anatomically connected neuronal population in vivo and directing electrode implantations to targeted nodes in the intricate system of brain networks., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction and Objectives: The CHADS2 score is a proven, essential tool for estimating cardioembolic risk (mainly stroke) in patients with nonvalvular atrial fibrillation, with the purpose of determining the indication for anticoagulant therapy. In this study we analyzed the use of CHADS2 in hypertensive patients without known atrial fibrillation in a Mediterranean population., Methods: The study included 887 hypertensive patients aged 65 years or older without atrial fibrillation or anticoagulant therapy, who attended a medical consultation. Data on the patients' main risk factors, cardiovascular history, and medication were collected, basic laboratory analyses and electrocardiography were performed, and the CHADS2 score (heart failure, hypertension, age ≥ 75 years, diabetes mellitus, and previous stroke or transient ischemic attack) was calculated. A clinical follow-up was carried out, recording hospital admissions for a stroke or transient ischemic attack. The median duration of follow-up was 804 days., Results: Mean age was 72.5 (SD,5.7) years, 46.6% were men, 27.8% had diabetes, and 8.6% were smokers. During follow-up, 40 patients were hospitalized for a stroke or transient ischemic attack (4.5%). The event-free survival analysis showed significant differences according to the CHADS2 score (log rank test, P < .001). On multivariate analysis, smoking and CHADS2 ≥3 were independent predictors of stroke or transient ischemic attack., Conclusions: The CHADS2 may be useful for estimating the risk of stroke or transient ischemic attack in hypertensive patients without known atrial fibrillation., (Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Neurons are able to express long-lasting and activity-dependent modulations of their synapses. This plastic property supports memory and conveys an extraordinary adaptive value, because it allows an individual to learn from, and respond to, changes in the environment. Molecular and physiological changes at the cellular level as well as network interactions are required in order to encode a pattern of synaptic activity into a long-term memory. While the cellular mechanisms linking synaptic plasticity to memory have been intensively studied, those regulating network interactions have received less attention. Combining high-resolution fMRI and in vivo electrophysiology in rats, we have previously reported a functional remodelling of long-range hippocampal networks induced by long-term potentiation (LTP) of synaptic plasticity in the perforant pathway. Here, we present new results demonstrating an increased bilateral coupling in the hippocampus specifically supported by the mossy cell commissural/associational pathway in response to LTP. This fMRI-measured increase in bilateral connectivity is accompanied by potentiation of the corresponding polysynaptically evoked commissural potential in the contralateral dentate gyrus and depression of the inactive convergent commissural pathway to the ipsilateral dentate. We review these and previous findings in the broader context of memory consolidation.

Background: Clinical inertia, the failure of physicians to initiate or intensify therapy when indicated, is a major problem in the management of hypertension and may be more prevalent in elderly patients. Overcoming clinical inertia requires understanding its causes and evaluating certain factors, particularly those related to physicians., Objective: The objective of our study was to determine the rate of clinical inertia and the physician-reported reasons for it., Methods: An observational, cross-sectional, multi-center study was carried out in a primary care setting. We included 512 physicians, with a consecutive sampling of 1,499 hypertensive patients with clinical inertia., Main Outcome Measure: Clinical inertia was defined when physicians did not modify treatment despite knowing that the therapeutic target had not been reached. Clinical inertia was considered to be justified (JCI) when physicians provided an explanation for not intensifying treatment and as not justified (nJCI) when no reasons were given., Results: JCI was observed in 30.1 % (95 % CI 27.8-32.4) of patients (n = 451) and nJCI in 69.9 % (95 % CI 67.6-72.2) (n = 1,058). JCI was associated with higher blood pressure (BP) values (both systolic and diastolic) and diabetes (p = 0.012) than nJCI. nJCI was associated with patients having an isolated increase of systolic or diastolic or high borderline BP values or cardiovascular disease., Conclusion: Physicians provided reasons for not intensifying treatment in poorly controlled patients in only 30 % of instances. Main reasons for not intensifying treatment were borderline BP values, co-morbidity, suspected white coat effect, or perceived difficulty achieving target. nJCI was associated with high borderline BP values and cardiovascular disease.

Aim: To determine whether there are gender differences in the epidemiological profile of atrial fibrillation (AF) and to characterise the clinical, biochemical, and therapeutic factors associated with AF., Methods: Each investigator (primary care physicians or physicians based in hospital units for hypertension treatment) recruited the first 3 patients with an age of ≥ 65 years and a clinical diagnosis of hypertension (ambulatory blood pressure monitoring and an electrocardiogram, were performed) on the first working day of the week for 5 wk and identified those individuals with atrial fibrillation. A binary logistic regression was performed, including all of the variables that were significant in the univariate analysis, to establish the variables that were associated with the presence of arrhythmia., Results: A total of 1028 patients were included in the study, with a mean age of 72.8 ± 5.8 years. Of these patients, 47.3% were male, 9% were smokers, 27.6% were diabetics, 48.3% had dyslipidaemia, 10.9% had angina, and 6.5% had experienced a myocardial infarction. Regarding gender differences, the men exhibited a larger waist circumference, a lower body mass index, less obesity, and a more extensive history of diabetes, smoking, ischaemic heart disease, kidney failure, peripheral arterial disease and carotid disease than the women. There were no differences, however, in the prevalence of AF between the men and the women (11.5% vs 9.2%, respectively; P = no significant). Regarding treatment, the women received antiplatelet agents and diuretics less frequently, but there were no other differences in the use of antihypertensive and antithrombotic therapies. In the multivariate analysis, AF in the total study population was associated with age, alcohol consumption, the presence of heart disease, and decreased glomerular filtration. In the women, AF was associated with all of the factors included in the overall analysis, as well as the presence of left ventricle hypertrophy. In contrast, in the men, the only risk factors associated with AF were age, the presence of heart disease and alcohol consumption., Conclusion: In patients with hypertension over 65 years of age, there are relevant gender differences in the factors associated with AF.

Objectives: To examine the evolution of hypertension management and blood pressure (BP) control in Spain in the last decade across PRESCAP 2002, 2006 and 2010., Methods: The methodology of the three studies was the same. They were multicenter and cross-sectional surveys aimed to determine BP control rates in hypertensive patients in primary care in Spain during 2002, 2006 and 2010, respectively. In each study, patients at least 18 years, with an established diagnosis of hypertension were included. Adequate BP control was defined as BP less than 140/90 mmHg in the general population (<130/85 mmHg in PRESCAP 2002 and less than 130/80 mmHg in PRESCAP 2006 and PRESCAP 2010 for patients with diabetes, chronic kidney disease and cardiovascular disease)., Results: A total of 12,754 patients (mean age 63.3 ± 10.8 years; 57.2% women), 10,520 patients (64.6 ± 11.3 years; 53.7% women) and 12,961 patients (66.3 ± 11.4; 52.0% women) were included in PRESCAP 2002, PRESCAP 2006 and PRESCAP 2010 studies respectively. With regard to BP control rates, 36.1% [95% confidence interval (CI) 35.2-36.9%], 41.4% (95% CI 40.5-42.4%) and 46.3% of patients (95% CI 45.4-47.1%) achieved BP goals in PRESCAP 2002, PRESCAP 2006 and PRESCAP 2010, respectively (P < 0.0001). In PRESCAP 2002, 56% of patients were on monotherapy, 35.6% were taking two drugs and 8.4% at least three drugs. In PRESCAP 2006 these numbers were 44.4, 41.1 and 14.5%, respectively, and in PRESCAP 2010 they were 36.4, 44.1 and 19.5%, respectively (P < 0.0001)., Conclusion: BP control rates have improved in Spain from 2002 to 2010. This may be related, at least in part, with the higher use of antihypertensive treatment, particularly combined therapy.

Background: Some studies have described a large number of hypertensive patients who are followed by a primary care physician without achieving adequate blood pressure (BP) control but whose treatment nevertheless is not intensified. It is not known whether physicians are aware of this clinical inertia and what factors are associated with this problem., Objective: The aim of this study was to describe the factors associated with clinical inertia in hypertensive patients., Methods: This was an observational, cross-sectional, multicentre study conducted in a network of primary care centres and hospital hypertension units in Spain. Using a consecutive sampling approach, 512 physicians selected 5077 hypertensive patients in whom they suspected poor BP control after chart review. The main variables documented were BP control and cardiovascular risk according to European Society of Hypertension guidelines, changes in treatment after visit, type of treatment, and healthcare setting. A binomial logistic regression multivariate analysis, adjusted for physician, was performed., Results: Of the selected patients, 70.9% had poor BP control according to measurements taken in the physician's office, and in 1499 (42.1%) of those poorly controlled patients, treatment was not intensified (clinical inertia). Factors associated with clinical inertia were as follows: being seen at a primary care centre (p < 0.001), not having left ventricular hypertrophy (p < 0.001) or microalbuminuria (p < 0.001), taking fixed-dose (p = 0.049) or free-dose (p = 0.001) combination therapy, BP measured in other settings (nurse's office, patient's home) than the physician's office (p = 0.034) or the pharmacy (p = 0.019), older age (p = 0.032), and lower systolic (p < 0.001) and diastolic (p < 0.001) BP. Of the hypertensive patients with clinical inertia, 90.2% (95% CI 88.7, 91.7) had high cardiovascular risk., Conclusions: Clinical inertia was associated with a profile that included older age, lack of co-morbid conditions and being seen at a primary care centre.

The SCORE table indiscriminately recommends the use of total cholesterol (SCORE-TC) or atherogenic index (SCORE-AI) for calculating cardiovascular (CV) risk. We evaluated reliability and agreement between both methods and the clinical implications for the identification of high CV risk. Observational study (n=8942) in a 40- to 65-year-old population. Spearman's Rho correlation was 0.987 (P<.001), the agreement intraclass correlation coefficient was 0.671 (IC 95% 0.413-0.796; with Bland-Altman's method, the average of the differences between models was 0.74. Kappa index was poor, 0.297 (P<.001) and positive specific agreement was 0.31. Discrepancies fitted individuals with high CV risk with SCORE-TC and not-high with SCORE-AI (4.7%) and 5.8% (n=518) of individuals were classified as high-risk according to SCORE-TC versus 1.1% (n=95) according to SCORE-AI. Poor agreement was found between SCORE-TC and SCORE-IA for identification of high cardiovascular risk individuals., (Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Chronic low-grade inflammation in obesity is characterized by macrophage accumulation in white adipose tissue (WAT) and abnormal cytokine production. We tested the hypothesis that grape-seed procyanidin extract (PE), with known anti-inflammatory and antioxidant effects, would improve local and systemic inflammation in diet-induced obesity rats. First, we analyzed the preventive effects of procyanidins (30 mg/kg per day) on rats fed a 60% kcal fat diet for 19 weeks. Second, we induced cafeteria diet obesity for 13 weeks to investigate the corrective effects of two PE doses (25 and 50 mg/kg per day) for 10 and 30 days. In the preventive model, PE group had reduced not only body weight but also plasmatic systemic markers of inflammation tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). The PE preventive treatment significantly showed an increased adiponectin expression and decreased TNF-α, interleukin-6 and CRP expression in mesenteric WAT and muscle TNF-α. A reduced NF-κB activity in liver is also observed which can be related to low expression rates of hepatic inflammatory markers found in PE group. Finally, PE dietary supplementation is linked to a reduced expression of Emr1 (specific marker of macrophage F4/80), which suggests a reduced macrophage infiltration of WAT. In the corrective model, however, only the high dose of PE reduced CRP plasma levels in the short treatment without changes in plasmatic TNF-α. In conclusion, orally ingested PE helps preventing imbalanced obesity cytokine pattern, but its corrective effects need to be further investigated. The dietary regular intake of food or drinks containing procyanidins might help prevent low-grade inflammatory-related diseases., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background and Objectives: Control of arterial blood pressure (BP) in hypertensive patients differs based on the evaluation procedure. This fact can be enhanced in subjects over 65 years of age. We have studied the degree of BP control with determinations in the office or ambulatory blood pressure monitoring (ABPM)., Methods: A multicenter, cross-sectional study was conducted in primary care (PC) and hypertension units in the Valencian Community. The first three hypertensive patients ≥ 65 years who attended the consultation on the first day of visits of the week of each investigator were included in the study. Cardiovascular risk factors, target organ damage and associated cardiovascular disease were recorded. Good clinical control values were defined as < 140/90 in the office and < 130/80 by ABPM for 24-hour according to 2007 ESH/ESC guidelines., Results: A total of 1,028 hypertensive patients were included, 52.7% of whom were women, with a mean age of 72.6 years. Mean clinical BP was 146.7/81.1 mmHg and 24-hour ABPM 128.5/70.8 mmHg. Ninety-two percent of the patients were treated with antihypertensive drugs (35.6% monotherapy and 56.4% with combinations of two or more drugs). Good clinical control was found in 35.3% of cases (CI 95%: 32.4-38.2) and 50.9% (CI 95%: 47.8-54.0) (P < .001) had good control of 24-hour BP in ABPM. Male gender, personal background of heart disease and stroke were associated with good control of hypertension (P < .01) in 24-hour ABPM., Conclusions: In hypertensive patients over 65 years, and compared to the clinical determination of BP, the evaluation of ABMP showed a better proportion of controlled subjects. These findings support a wider use of ABPM to evaluate the control of BP in this population., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Natural plant extracts are candidates for the development of new functional foods. Most of them are usually complex mixtures of molecules of uncertain bioavailability that are often partially metabolized before they finally reach the target cells IN VIVO. IN VITRO studies of the bioactivity of these extracts suggest that their direct application to some cell cultures might be a long way from becoming a reality. To overcome this limitation, we seeded Caco-2 cells onto culture inserts and after 21 days, cocultured these with INS-1E on the base of the well. After 24 hours of coculture, TEER (transepithelium electrical resistance) measurements indicated no changes in the permeability of the Caco-2 barrier. We also found no changes in either the ability of Caco-2 cells to metabolize the flavan-3-ol component of a grape-seed procyanidin-rich extract, or in the flavanols' ability to pass through the barrier. However, the expression of the Caco-2 SGLT-1 gene increased due to the coculture. GSIS (glucose stimulated insulin secretion) was maintained in the INS-1E cells with higher levels of insulin secretion despite the fact that the insulin gene expression was unmodified by the cocultivation. Furthermore, we found that in some of the assays requiring several medium changes there was a tendency to lose β-cells. Neutral red assay showed that seeded cells should only be cocultured for a short time to obtain a higher consistency. In conclusion, four hours coculture with Caco-2 cells and INS-1E is a suitable method for checking the bioactivity of natural plant extracts of unknown bioavailability on β-cells., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction and Objectives: Age and arterial hypertension are two of the main factors associated with atrial fibrillation and an increased risk of embolism. The objective of this study was to determine the prevalence of atrial fibrillation and the extent of antithrombotic use in hypertensive patients aged ≥65 years in the Spanish region of Valencia., Methods: Each study investigator enrolled the first three hypertensive patients aged ≥65 years who came for a consultation on the first day of each week for 5 weeks. Each patient's risk factors, history of cardiovascular disease, CHADS(2) score and medical treatment were noted and an ECG was recorded. Data were analyzed centrally. A patient was regarded as having atrial fibrillation if it was observable on the ECG or reported in medical records., Results: The study included 1,028 hypertensive patients with a mean age of 72.8 years. Overall, 10.3% had atrial fibrillation: in 6.7%, it was observable on the ECG while 3.6% were in sinus rhythm but had a history of the condition. Factors associated with atrial fibrillation were age, alcohol intake, structural heart disease and glomerular filtration rate. In total, 76.2% of patients with ECG evidence of atrial fibrillation and a CHADS(2) score >1 were taking anticoagulants compared with 41.7% of those who had a history of the condition but were currently in sinus rhythm., Conclusions: The prevalence of atrial fibrillation in our group of hypertensives was 10.3%; in 1.7%, it was previously undiagnosed. Antithrombotic use was high in patients with current atrial fibrillation, but lower in those who had experienced an episode previously., (Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Introduction and Objectives: Age and arterial hypertension are two of the main factors associated with atrial fibrillation and an increased risk of embolism. The objective of this study was to determine the prevalence of atrial fibrillation and the extent of antithrombotic use in hypertensive patients aged >or=65 years in the Spanish region of Valencia., Methods: Each study investigator enrolled the first three hypertensive patients aged >or=65 years who came for a consultation on the first day of each week for 5 weeks. Each patient's risk factors, history of cardiovascular disease, CHADS2 score and medical treatment were noted and an ECG was recorded. Data were analyzed centrally. A patient was regarded as having atrial fibrillation if it was observable on the ECG or reported in medical records., Results: The study included 1,028 hypertensive patients with a mean age of 72.8 years. Overall, 10.3% had atrial fibrillation: in 6.7%, it was observable on the ECG while 3.6% were in sinus rhythm but had a history of the condition. Factors associated with atrial fibrillation were age, alcohol intake, structural heart disease and glomerular filtration rate. In total, 76.2% of patients with ECG evidence of atrial fibrillation and a CHADS2 score >1 were taking anticoagulants compared with 41.7% of those who had a history of the condition but were currently in sinus rhythm., Conclusions: The prevalence of atrial fibrillation in our group of hypertensives was 10.3%; in 1.7%, it was previously undiagnosed. Antithrombotic use was high in patients with current atrial fibrillation, but lower in those who had experienced an episode previously.

Background: The relationship between basal heart rate (HR) and the occurrence of myocardial ischemia, sudden death, cardiovascular mortality have been described. Therefore, further studies are warranted to evaluate the behaviour of heart rate in different scenarios. We sought to determine whether ambulatory heart rate is associated with the presence of target organ damage (TOD) in hypertensive patients., Patients and Methods: Crossectional study of essential hypertensive patients in whom a twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed. The relationship between TOD and 24 hour ambulatory heart rate (HR) was analyzed., Results: Five hundred and sixty-six patients with arterial hypertension were included (55.8% male, mean age 59.9 +/- 14.2 years). 15% were smokers, 62.2% had dyslipidemia, 18.4% diabetes mellitus. Heart rate values were higher during activity as compared to the resting period (72.8 vs 63.3 bpm, p < 0.001). Heart rate, in both periods, was not associated with the presence of TOD. Nevertheless, the patients with nocturnal HR > or = 65 bpm have high risk and a high prevalence of TOD. This relationship was also present in multivariate analysis (HR 2.41; CI 95% 1.41-4.11; p=0.001)., Conclusion: An elevated nocturnal HR, > or = 65 bpm, obtained with ABPM registry, is associated with the presence of TOD in hypertensive patients. ABPM is a powerful tool for hypertensive patients not only to monitor BP control but also to obtain information on HR which may provide additional information about current and future cardiovascular risk.

Ambulatory blood pressure (BP) monitoring has become useful in the diagnosis and management of hypertensive individuals. In addition to 24-hour values, the circadian variation of BP adds prognostic significance in predicting cardiovascular outcome. However, the magnitude of circadian BP patterns in large studies has hardly been noticed. Our aims were to determine the prevalence of circadian BP patterns and to assess clinical conditions associated with the nondipping status in groups of both treated and untreated hypertensive subjects, studied separately. Clinical data and 24-hour ambulatory BP monitoring were obtained from 42,947 hypertensive patients included in the Spanish Society of Hypertension Ambulatory Blood Pressure Monitoring Registry. They were 8384 previously untreated and 34,563 treated hypertensives. Twenty-four-hour ambulatory BP monitoring was performed with an oscillometric device (SpaceLabs 90207). A nondipping pattern was defined when nocturnal systolic BP dip was <10% of daytime systolic BP. The prevalence of nondipping was 41% in the untreated group and 53% in treated patients. In both groups, advanced age, obesity, diabetes mellitus, and overt cardiovascular or renal disease were associated with a blunted nocturnal BP decline (P<0.001). In treated patients, nondipping was associated with the use of a higher number of antihypertensive drugs but not with the time of the day at which antihypertensive drugs were administered. In conclusion, a blunted nocturnal BP dip (the nondipping pattern) is common in hypertensive patients. A clinical pattern of high cardiovascular risk is associated with nondipping, suggesting that the blunted nocturnal BP dip may be merely a marker of high cardiovascular risk.

Objective: To assess the relationship between different serum lipid profiles and the prevalence of established cardiovascular disease (CVD) in an elderly population., Research Design and Methods: An analysis was undertaken of the PREV-ICTUS population-based study on Spanish subjects aged > or =60 years. The following definitions were used: abnormal LDL cholesterol (LDL-C): > or =130 mg/dl (> or =3.3 mmol/L), or > or =100 mg/dl (> or =2.5 mmol/L) in those with diabetes or CVD, or treatment with any hypolipidaemic drug; low HDL cholesterol (HDL-C): <40 mg/dl (<1 mmol/L) (men), or <50 mg/dl (<1.3 mmol/L) (women), and abnormal triglycerides (TG): > or =150 mg/dl (> or =1.7 mmol/L) or treatment with fibrates. We defined eight groups: A (normal lipid profile), B (isolated abnormal LDL-C), C (isolated abnormal TG), D (isolated low HDL-C), E (abnormal LDL-C and HDL-C), F (abnormal LDL-C and TG), G (abnormal TG and HDL-C), H (abnormal LDL-C, HDL-C and TG). A multivariate analysis was performed to assess the relationship between each lipid profile and CVD., Results: A total of 6010 subjects (mean age 71.7 years, 53.5% women, 73.2% with hypertension, 29.2% with diabetes mellitus, 24.3% with CVD), were included in the analysis. LDL-C elevation was present in 78.1%, 23.3% had low HDL-C and 35.7% abnormal TG. Combined dyslipidaemias were frequent (40.3%). Odds ratios (95% confidence intervals) for CVD, compared with those with a normal lipid profile, were 2.07 (1.24-3.46) for abnormal HDL-C (p = 0.005), 4.09 (3.10-5.39) for abnormal LDL-C; 6.41 (4.59-8.95) for abnormal LDL-C plus HDL-C, 5.33 (3.98-7.14) for abnormal LDL-C plus TG and 7.59 (5.51-10.5) for those with the three parameters altered (all p < 0.001). Compared with those with isolated LDL-C elevation, those with abnormal LDL-C plus HDL-C had 1.57 (1.30-1.97) higher odds of having CVD (p < 0.001), the figures being 1.30 (1.11-1.53) for those with abnormal LDL-C plus TG and 1.86 (1.52-2.28) for those with abnormal LDL-C, TG plus HDL-C (p < 0.001)., Conclusions: Lipid abnormalities are frequent in the elderly, and are associated with the presence of CVD. Low HDL-C and/or abnormal TG levels, when added to abnormal LDL-C, are associated with a higher prevalence of CVD, suggesting the advisability of a comprehensive lipid evaluation and treatment earlier in life.

Objective: The aim of this study is to evaluate the effect of trimetazidine (TMZ) on myocardial systolic dysfunction resulting from an isolated episode of induced coronary ischemia., Methods: In a double-blinded randomized design we studied 13 mongrel anesthetized dogs of either sex (6 of them treated with oral TMZ previously). The anterior descending coronary artery was totally occluded during 15 minutes followed by 60 minutes of reperfusion. Global and regional cardiac variables were recorded in control and ischemic areas., Results: There were no significant differences between TMZ and placebo series with respect to global cardiac function variables. Both series showed no significant variations in global variables during the ischemia-reperfusion process. The shortening fraction in the ischemic area fell significantly during the ischemic period in both TMZ and placebo series reaching dyskinetic values. Myocardial contractility dysfunction persisted after 60 minutes of reperfusion in both series with no significant differences (41% vs 50% placebo)., Conclusions: Contrary to shorter and repeated occlusion periods, myocardial contractility recovery after a complete episode of ischemia did not show significant differences between TMZ-treated and placebo series.

Introduction and Objectives: The need for more specific, more sensitive and earlier biochemical markers of acute myocardial infarction, has led to the development of alternative methods to CK-MB). The aim of this work is to assess the usefulness of TnT measurement, in comparison with other markers for detecting transitory ischemic processes without necrosis in some experimental models., Methods: The plasma levels of Troponine T, CK, CK-MB and adenosine were assessed as markers of ischemic myocardial injury. Two protocols were used: in Series I and II very brief (2 min ischemia with 3-min reperfusion) repeated (20 episodes) ischemias were induced, while Series III involved a single 15-min ischemia with a 60-min reperfusion. In Series I the coronary occlusor was placed close to the anterior descending coronary artery (AD); in Series II and III it was placed distally in the AD. Blood samples were taken from the peripheral vein (PVB) and corresponding coronary segment vein; in a basal situation, during ischemia, upon reperfusion, after 24 hours, and after 5 and 10 days. The plasma levels of adenosine, troponine T, CK and CK-MB as well as general and regional function parameters were measured., Results: In Series I we observed hypokinesis that lasted 10 days, reaching its maximum on days 4-5. In Series II and III regional function was restored by 24 hours. CK and CK-MB showed similar behaviour; they rose significantly when the chest was opened (p < 0.05) reaching the highest value at 24 hours in all the series. Adenosine rose significantly only during reperfusion (p < 0.05). Troponine T increased after ischemia but not before, remained high for 5 days in all series (PVB)., Conclusions: Troponine T rises in absence of necrosis, preferably when the ischemia is longer.

Objective: To analyze whether nitroglycerin and nifedipine can reduce myocardial stunning due to very brief, repeated coronary ischemias., Material and Methods: In 33 anaesthetized and open chest dogs, the lengthening and shortening fractions were analyzed with ultrasonic crystals in the ischemic and control myocardial areas. Twenty repeated coronary occlusions of 2 minutes each, with a recovery time of 3 minutes between each occlusion, were induced. At the beginning of the experiment, nitroglycerin (0.3 mg i.v. and 80 micrograms/kg/min perfusion) was administered in series A (n = 8), nifedipine (5 mu/kg i.v. and 1 microgram/kg/min perfusion) in series B (n = 9). The results were compared with control results (n = 16) without drugs., Results: Changes in the shortening fraction of the ischemic area during coronary occlusions were similar in all three series; after the last occlusion the shortening fraction in the control series was -14.9% with respect to basal values, -14.6% in series A and -16.6% in series B. Sixty minutes after the last ischemia, the shortening fraction impairment in respect to the basal values was larger in the control series (-18.9%) and in series A (-16.9%). In series B there was recovery (-13.5%) (p < 0.05 vs control series)., Conclusions: Our study indicates that nitroglycerin does not seem to have cardioprotective effects against brief, repeated ischemia. However, nifedipine decreases postischemic dysfunction due to this model of ischemia, probably by avoiding the intracellular Ca overload produced during cardiac ischemia.

Headache is one of the most frequent complications of the subarachnoid puncture. Physiopathology and the different clinical factors involved in this type of headache are reviewed. The treatment is based in two types of procedures: those increasing cerebrospinal fluid production and those trying to decrease its leakage, like the epidural blood patch.