Early detection and management of the high-risk patient with elevated blood pressure

Severe or important blood pressure elevations are associated with the risk of cardiovascular disease. However, a significant proportion of myocardial infarctions and strokes occur in subjects with only slight elevations or even with normal blood pressure. Both the coexistence of other cardiovascular risk factors, such as diabetes or dyslipidemia, or those recently recognized, such as elevations of C-reactive protein or abdominal obesity and metabolic syndrome, or the presence of target organ damage, such as microalbuminuria, left ventricular hypertrophy, mild renal dysfunction or increased intima-media thickness, all indicate the existence of a high cardiovascular risk in mild hypertensives or in subjects with normal or high-normal blood pressure. Unfortunately, these high-risk patients are often not recognized and thus under-treated

Effects of Eprosartan on Target Organ Protection

Hypertension is the most important cardiovascular risk factor for stroke. Blood pressure reduction by antihypertensive treatment is clearly efficacious in the prevention of stroke (both primary and secondary), although no clear differences have yet been observed between antihypertensive drug classes. However, a recent study reported the clear superiority of the angiotensin-receptor blocker eprosartan over the calcium channel blocker nitrendipine in cardiovascular protection of hypertensive patients with a previous stroke. Comparative studies using angiotensin-receptor blockers have also suggested the superiority of this class of drugs on primary stroke prevention. This effect may be linked to their beneficial actions on left ventricular hypertrophy, atrial enlargement, and supraventricular arrhythmias, endothelial dysfunction, inflammation, and remodelling, as well as a direct neuroprotective effect mediated through the stimulation of the angiotensin II type-2 receptor. In addition, a sympathoinhibition observed with the renin–angiotensin system blockers and particularly demonstrated with eprosartan, may help to explain the better cardiovascular and cerebrovascular protection in comparison with the calcium antagonist nitrendipine

Estudio cinético de los sistemas de transporte transmembranoso de sodio en la hipertensión arterial esencial

[spa] La hipertensión arterial es la enfermedad más frecuente de cuantas afectan a la especie humana. Su prevalencia actual se cifra en el 20 % y 25 % de la población mundial y su importancia radica en el hecho de ser uno de los principales factores de riesgo del padecimiento de enfermedades cardiovasculares que representan, sin lugar a dudas, la primera causa de muerte en la población occidental.Frente a un pequeño porcentaje de pacientes en los que se demuestra una causa definida de hipertensión arterial, en el resto (más del 95 % en poblaciones no seleccionadas) no se conoce su etiología y se clasifican dentro del grupo llamado HTA esencial.La investigación sobre la etiopatogenia de la HTA esencial ha puesto de manifiesto el carácter hereditario de la misma. Asimismo, estudios epidemiológicos, experimentales y clínicos han permitido establecer una inequívoca relación entre el consumo excesivo de sal en la dieta y la etiopatogenia de la HTA esencial.En los últimos años se ha producido un importante avance en el conocimiento del metabolismo del Na+ a nivel molecular y, más concretamente, de los mecanismos que regulan su transporte a través de las membranas celulares. La caracterización de estos sistemas de transporte iónico ha permitido la detección de anomalías de los mismos tanto en las células de los pacientes afectos de HTA esencial como en las de diferentes cepas de ratas hipertensas. Aunque los estudios en la especie humana se han realizado fundamentalmente en células sanguíneas, las alteraciones en ellas descritas han podido reproducirse en neuronas simpáticas, fibras musculares lisas vasculares y células tubulares renales de los animales de experimentación. No obstante, los resultados obtenidos por diferentes grupos de investigadores han sido contradictorios. Ello es probablemente debido a las diferentes metodologías empleadas, a que gran número de estudios se han realizado midiendo la actividad de uno o más sistemas de transporte a una concentración fija de cationes intra y extracelulares y, tal vez, a que la población hipertensa es heterogénea en cuanto a las anomalías de sus sistemas de transporte de Na+.Las alteraciones estables descritas hasta el momento son capaces de aumentar, probablemente de manera transitoria, la concentración intracelular de Na+, lo que a nivel de la fibra muscular lisa vascular puede promover un aumento en el contenido de Ca++, a través de la estimulación del contratransporte Na+-Ca++, que podría ser responsable del aumento del tono vascular y, por tanto, de las resistencias vasculares periféricas, alteración común primordial en los pacientes hipertensos.El objetivo de la tesis doctoral ha sido la detección de las posibles anomalías en los principales sistemas de transporte transmembranoso de Na+ (ATPasa Na+-K+, cotransporte Na+-K+-Cl-, contratransporte Na+-Li+ y difusión pasiva de Na+) en los eritrocitos de pacientes hipertensos esenciales. La detección de estas anomalías se ha efectuado a dos niveles. Por un lado, se han determinado los flujos de Na+ dependientes de los diferentes sistemas de transporte en eritrocitos con una concentración intracelular de Na+ fisiológica. Por otro, se han caracterizado las anomalías desde el punto de vista cinético en base a dos parámetros fundamentales, la velocidad máxima (Vmax) y la afinidad aparente del sistema para el Na+ intracelular (K50%). Asimismo, se han intentado definir subgrupos de hipertensos esenciales atendiendo a las anomalías detectadas y a la existencia de características clínicas diferenciales. El estudio de los sistemas de transporte se ha llevado a cabo después de someter a los hematíes a una sobrecarga sódica o potásica «in vitro», mediante la incubación de las células en diferentes soluciones de fosfato sódico o potásico. Ello ha permitido la obtención de 5 suspensiones celulares con diferentes concentraciones citosólicas de Na+. El flujo de sodio dependiente de la actividad ATPasa se ha considerado como el componente sensible a la ouabaína de la extrusión neta de Na+a través de la membrana eritrocitaria. El componente resistente a la ouabaína e inhibido por la bumetanida se ha considerado como el flujo de Na+ catalizado por el cotransporte Na+-K+-Cl-. El flujo de Na+ dependiente de la actividad del contratransporte Na+-'Li+ se ha considerado como el componente de la extrusión neta de Na+, resistente a la ouabaína y bumetanida, que es estimulado por Li+. Finalmente, el componente de la extrusión de Na+ resistente a la ouabaína y bumetanida en un medio rico en Mg++ y sacarosa se ha asumido como el flujo pasivo.El flujo dependiente de cada sistema de transporte se ha determinado en función de la concentración intracelular de Na+, lo que ha posibilitado el cálculo de los parámetros cinéticos (Vmax y K50 %) de cada sistema de transporte activo. Se han estudiado los sistemas de transporte de Na+ en los eritrocitos de 30 individuos normales y 72 pacientes afectos de HTA esencial.Las principales conclusiones de los resultados obtenidos han sido:El contenido intraeritrocitario de Na+, los flujos dependientes de los diferentes sistemas de transporte, así como sus características cinéticas, no tienen ninguna relación con la edad, sexo o cifras de tensión arterial en los individuos normotensos.Los flujos medios de Na+ dependientes de la ATPasa 5 Na+-K+, cotransporte Na+-K+-Cl- y la constante de permeabilidad pasiva para el Na+ (K,Na) son similares en la población de hipertensos esenciales y en los individuos control. Por el contrario, el flujo medio de Na+ dependiente del contratransporte Na+-Li+ es significativamente superior en la población hipertensa (p = 0,0105).Al utilizar el intervalo de confianza del 95 % del grupo control como criterio de normalidad de los diferentes parámetros, en el 60 % de los hipertensos no se detecta ninguna anomalía del transporte de Na+.El estudio de los sistemas de transporte de Na+ en eritrocitos con una concentración intracelular de Na+ fisiológica es poco útil tanto para discriminar a los pacientes hipertensos de los controles como para clasificar a los primeros en diferentes subgrupos.En la población de hipertensos esenciales, la velocidad máxima del sistema (Vmax) y la constante de afinidad aparente para el Na+ intracelular (K50 %) de la ATPasa y cotransporte no difieren de las del grupo control. Sin embargo, la Vmax (p < 0,0001) y la K50 % (p = 0,0079) del contratransporte son significativamente superiores en los pacientes hipertensos.Al utilizar el intervalo de confianza del 95 % del grupo control como criterio de normalidad de los diferentes parámetros cinéticos, en el 93 % de los hipertensos esenciales se detecta alguna anomalía de los sistemas de transporte de Na+.El 16,67 % de los pacientes presenta un aumento en la K50 % de la ATPasa por encima de los valores altos de la normalidad. A estos hipertensos los denominamos "Bomba". El 27,7 % presenta un aumento en los valores de la K50 % del cotransporte. A estos hipertensos los denominamos "Co". El 37,5 % presenta un aumento en la velocidad máxima del contratransporte. A ellos los denominamos "Contra +". El 6,94 % presenta un aumento de la constante de permeabilidad por difusión pasiva. A ellos los denominamos "FP +". El 4,2 presenta más de una anomalía en sus sistemas de transporte transmembranoso de Na+. El 6,94 % no presenta ninguna anomalía cinética de sus sistemas de transporte. A ellos los hemos denominado hipertensos "Nulos".El estudio de las características cinéticas de los sistemas de transporte transmembranoso de Na+ permite discriminar a la mayoría de los pacientes hipertensos de los normotensos, así como clasificarlos atendiendo a la anomalía fundamental que presentan.Salvo las diferencias de tensión arterial entre los "Co-" y "Contra+", los subgrupos obtenidos no presentan características clínicas que los diferencien entre sí.[eng] Several epidemiological, experimental and clinical studies have suggested the involvement of an «inorn error of Na+ metabolism» in the pathogenesis of essential hypertension. This likely implies the presence of inherited defects in Na+ transport proteins.Na+ transport has been extensively investigated in erythrocytes from essential hypertensive patients. However, most studies were done measuring the activity of one or more Na+ transport systems at a constant internal and external cation content. Therefore, the reported results varied from laboratory to laboratory and were unable to provide a coherent understanding of Na+ transport in hypertension.Abnormalities of sodium transport in hypertension are much more complexes than a simple increase or decrease in the activity of one or more Na+ transport systems. Indeed, a minimum kinetic approach to this field requires measurement of apparent affinities (K50 %) and maximal translocation rates (Vmax) for every Na+ transport system.We have performed a kinetic analysis of the interaction of internal Na+ with four different transport pathways (Na+-K+ ATPase, Na+-K+ cotransport, Na+-Li+ countertransport and Na+ leak) in erythrocytes from 72 essential hypertensive patients and 30 normotensive controls. The Vmax and K50 % of Na+-Li+ countertransport were significantly higher in hypertensive group than in normotensives, whereas Vmax and K50- O¡() ofNa+-K+ ATPase and Na+-K+ cotransport and the rate constant of Na+ leak did no differ between hypertensives and normotensives.When the upper end (95 % confidence limits) of the normotensive group was used as a cut-off point of the normality, 67 (93 %) of essential hypertensive patients exhibited some abnormalities in their Na+ transport systems. 12 (16.7 %) showed increased values of K50 % of Na+-K+ ATPase (Pump «-» hypertensives). 20 (27.7 %) exhibited increased values of K50 % of the Na+-K+ cotransport (Co «-» hypertensives). 27 (37.5 %) reveal increased values of Vmax of the Na+-Li+ countertransport (Counter «+» hypertensives) and 5 (6.9 OJo) showed increased values in the rate constant of Na+ leak (Leak «+» hypertensives). FinalIy 3 (4.2 %) patients present more than one abnormality in their transport systems.In target cells of hypertension such as vascular wall renal tubules or noradrenergic endings, the abnormalities reported above could raise the internal Na+ concentration thus leading to hypertension, through interaction with catecholamines and Ca++ transport

Current Situation of Medication Adherence in Hypertension

Despite increased awareness, poor adherence to treatments for chronic diseases remains a global problem. Adherence issues are common in patients taking antihypertensive therapy and associated with increased risks of coronary and cerebrovascular events. Whilst there has been a gradual trend toward improved control of hypertension, the number of patients with blood pressure values above goal has remained constant. This has both personal and economic consequences. Medication adherence is a multifaceted issue and consists of three components: initiation, implementation, and persistence. A combination of methods is recommended to measure adherence, with electronic monitoring and drug measurement being the most accurate. Pill burden, resulting from free combinations of blood pressure lowering treatments, makes the daily routine of medication taking complex, which can be a barrier to optimal adherence. Single-pill fixed-dose combinations simplify the habit of medication taking and improve medication adherence. Re-packing of medication is also being utilized as a method of improving adherence. This paper presents the outcomes of discussions by a European group of experts on the current situation of medication adherence in hypertension

Utility of FEV1/FEV6 index in patients with multimorbidity hospitalized for decompensation of chronic diseases

Spirometry remains essential for the diagnosis of airway obstruction. Nevertheless, its performance in elderly hospitalized patients with multimorbidity can be difficult. The aim of this study is to assess the utility of the COPD-6 portable device in this population. We included all patients hospitalized for exacerbation of chronic diseases in a medical ward specialized in the care of multimorbidity patients, between September 2017 and May 2018. A questionnaire including sociodemographic, cognitive and functional impairment, among other variables, was completed the last day of admission. Subsequently, patients attempted to perform three valid respiratory manoeuvres with the COPD-6 device and then conventional spirometry. A total of 184 patients were included (mean age of 79.61 years, 55% men). Forty-seven (25.54%) patients were able to perform complete spirometric manoeuvres and 99 (53.8%) could perform a valid FEV1/FEV6 determination. The inability to perform a valid spirometry was related with the patient's age, functional physical disability, cognitive impairment or the presence of delirium or dysphagia during admission. Only 9% of patients with a Mini Mental Cognitive Examination (MMEC) lower than 24 points could perform a valid spirometry. Of the patients with an MMEC < 24 points and unable to perform spirometry, 34% were able to complete the FEV1/FEV6 manoeuvres. No differences were found in the Charlson index, multimorbidity scale, number of domiciliary drugs, or length of stay between those patients able and those not able to perform respiratory manoeuvres. The agreement between the values for FEV1 measured with COPD-6 and those observed in the spirometry was good (r: 0.71; p<0.0001). Inability to perform a valid spirometry during hospitalization in elderly patients with multimorbidity is frequent and related with functional and cognitive impairment. FEV1/FEV6 determination using the COPD-6 portable device allows an important percentage of the patients with limitations to complete spirometric measurement

Multimorbidity gender patterns in hospitalized elderly patients

Patients with multimorbidity and complex health care needs are usually vulnerable elders with several concomitant advanced chronic diseases. Our research aim was to evaluate differences in patterns of multimorbidity by gender in this population and their possible prognostic implications, measured as in-hospital mortality, 1-month readmissions, and 1-year mortality. We focused on a cohort of elderly patients with well-established multimorbidity criteria admitted to a specific unit for chronic complex-care patients. Multimorbidity criteria, the Charlson, PROFUND and Barthel indexes, and the Pfeiffer test were collected prospectively during their stays. A total of 843 patients (49.2% men) were included, with a median age of 84 [interquartile range (IQR) 79-89] years. The women were older, with greater functional dependence [Barthel index: 40 (IQR:10-65) vs. 60 (IQR: 25-90)], showed more cognitive deterioration [Pfeiffer test: 5 (IQR:1-9) vs. 1 (0-6)], and had worse scores on the PROFUND index [15 (IQR:9-18) vs. 11.5 (IQR: 6-15)], all p <0.0001, while men had greater comorbidity measured with the Charlson index [5 (IQR: 3-7) vs. 4 (IQR: 3-6); p = 0.002]. In the multimorbidity criteria scale, heart failure, autoimmune diseases, dementia, and osteoarticular diseases were more frequent in women, while ischemic heart disease, chronic respiratory diseases, and neoplasms predominated in men. In the analysis of grouped patterns, neurological and osteoarticular diseases were more frequent in females, while respiratory and cancer predominated in males. We did not find gender differences for in-hospital mortality, 1-month readmissions, or 1-year mortality. In the multivariate analysis age, the Charlson, Barthel and PROFUND indexes, along with previous admissions, were independent predictors of 1-year mortality, while gender was non-significant. The Charlson and PROFUND indexes predicted mortality during follow-up more accurately in men than in women (AUC 0.70 vs. 0.57 and 0.74 vs. 0.62, respectively), with both p<0.001. In conclusion, our study shows differing patterns of multimorbidity by gender, with greater functional impairment in women and more comorbidity in men, although without differences in the prognosis. Moreover, some of these prognostic indicators had differing accuracy for the genders in predicting mortality

Clinical Experience with Diltiazem in the Treatment of Cardiovascular Diseases

Cardiovascular diseases are the leading cause of death in the world. Coronary artery diseases, atrial fibrillation or hypertensive heart disease, are among the most important cardiovascular disorders. Hypertension represents a significant risk factor for cardiovascular mortality; thus, control of high blood pressure has become a priority to prevent major complications. Although the choice of drugs for treating hypertension remains controversial, extensive clinical evidences point to calcium channel blockers as first-line agents. Diltiazem, a non-dihydropyridine calcium channel blocker, is an effective and safe antihypertensive drug, alone or in combination with other agents. Diltiazem lowers myocardial oxygen demand through a reduction in heart rate, blood pressure, and cardiac contractility, representing also a good alternative for the treatment of stable chronic angina. Furthermore, diltiazem reduces conduction in atrioventricular node, which is also useful for heart rate control in patients with atrial fibrillation. In this review, clinical experts highlight studies on diltiazem effectiveness and safety for the treatment of several cardiovascular diseases and make evidence-based recommendations regarding the management of diltiazem in the clinical pracSponsorship for this review and the article processing charges was funded by Lacer Spain. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Writing assistance in the preparation of this manuscript was provided by Patricia Rodriguez, PhD, and editorial assistance was provided by Springer Healthcare. Support for this assistance was funded by Lacer Spain

2012 ranking in research in Spanish public universities

Antecedentes: para garantizar la utilidad de las políticas de promoción de la investigación de las instituciones educativas, en los últimos años se están desarrollando estudios que analizan diversos indicadores, con la intención de valorar posibles cambios en el futuro. El objetivo de este trabajo es actualizar el ranking de producción y productividad en investigación de las universidades públicas españolas, con los datos del año 2012. Método: se sigue la misma metodología que en los años anteriores. Se evalúan siete indicadores: artículos en revistas indexadas en el JCR, tramos de investigación, proyectos I+D, tesis doctorales, becas FPU, doctorados con Mención hacia la Excelencia y patentes. Resultados: en los resultados obtenidos en el ranking global se perciben diferencias entre las universidades que poseen una mayor producción (Universidad de Barcelona, Complutense de Madrid y Universidad de Granada) y las que tienen una mayor productividad (Pompeu Fabra, Pablo de Olavide y Miguel Hernández de Elche). Conclusiones: al comparar los resultados con la edición anterior de 2011 se puede ver que las tres universidades más productivas se mantienen en los mismos puestos.Background: In order to guarantee the usefulness of promotion policies for the investigation of educational institutions, in recent years studies analyzing different indicators have been developed, with the intention of valuing possible changes in the future. The objective of this work is to update the research production and productivity ranking of Spanish public universities, using data from 2012. Method: The same methodology as previous years has been followed. Seven indicators have been evaluated: articles from journals indexed in the JCR, research lines, R+D projects, doctoral theses, Spanish research and training grants, doctorate courses awarded a mention of excellence and patents. Results: Amongst the results obtained in the global ranking there are differences between the universities with a higher production (University of Barcelona, Complutense University of Madrid and the University of Granada) and those with a higher productivity (Pompeu Fabra, Pablo de Olavide and Miguel Hernández de Elche). Conclusions: When comparing the results to those of 2011, it can be observed that the three most productive universities remain in the same positions

Guía de actuación para el farmacéutico comunitario en pacientes con hipertensión arterial y riesgo cardiovascular: Documento de consenso

La hipertensión arterial (HTA) es un problema de salud estrechamente relacionado con un aumento del riesgo de padecer una enfermedad cardiovascular. Además, la HTA puede producir o empeorar la lesión de ciertos órganos diana, lo que también puede influir negativamente en el pronóstico cardiovascular del paciente. En España, la HTA es una condición muy frecuente, afectando a unos diez millones de sujetos adultos. Por su accesibilidad y formación especializada en materia de medicamentos, el farmacéutico comunitario puede jugar un papel clave en la detección y seguimiento del paciente con HTA. Hasta la fecha, se han publicado numerosas guías clínicas sobre la atención a pacientes con HTA, dirigidas principalmente a médicos. Sin embargo, cada vez es más evidente la necesidad de que todos los profesionales de la salud participen en la atención integral a los pacientes con HTA y riesgo cardiovascular (RCV). La cooperación entre farmacéutico, médico, personal de enfermería y otros profesionales sanitarios es imprescindible para conseguir resultados que optimicen la prevención cardiovascular y mejoren la calidad de vida del paciente. Así, a fin de promover la gestión compartida de los pacientes con HTA y RCV se publica este documento, cuyo principal destinatario es el farmacéutico comunitario. El presente documento pretende ser una herramienta de referencia que dé soporte a los programas de atención farmacéutica al paciente con HTA y RCV que se están desarrollando actualmente en las oficinas de farmacia. El texto ha sido desarrollado de forma consensuada entre expertos de la Sociedad Española de Hipertensión-Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA), la Sociedad Española de Farmacia Comunitaria (SEFAC) y el Grupo de Investigación en Atención Farmacéutica de la Universidad de Granada (GIAF-UGR

Underdiagnosis and prognosis of chronic obstructive pulmonary disease after percutaneous coronary intervention: a prospective study

BACKGROUND Retrospective studies based on clinical data and without spirometric confirmation suggest a poorer prognosis of patients with ischemic heart disease (IHD) and chronic obstructive pulmonary disease (COPD) following percutaneous coronary intervention (PCI). The impact of undiagnosed COPD in these patients is unknown. We aimed to evaluate the prognostic impact of COPD - previously or newly diagnosed - in patients with IHD treated with PCI. METHODS: Patients with IHD confirmed by PCI were consecutively included. After PCI they underwent forced spirometry and evaluation for cardiovascular risk factors. All-cause mortality, new cardiovascular events, and their combined endpoint were analyzed. RESULTS: A total of 133 patients (78%) male, with a mean (SD) age of 63 (10.12) years were included. Of these, 33 (24.8%) met the spirometric criteria for COPD, of whom 81.8% were undiagnosed. IHD patients with COPD were older, had more coronary vessels affected, and a greater history of previous myocardial infarction. Median follow-up was 934 days (interquartile range [25%-75%]: 546-1,160). COPD patients had greater mortality (P=0.008; hazard ratio [HR]: 8.85; 95% confidence interval [CI]: 1.76-44.47) and number of cardiovascular events (P=0.024; HR: 1.87; 95% CI: 1.04-3.33), even those without a previous diagnosis of COPD (P=0.01; HR: 1.78; 95% CI: 1.12-2.83). These differences remained after adjustment for sex, age, number of coronary vessels affected, and previous myocardial infarction (P=0.025; HR: 1.83; 95% CI: 1.08-3.1). CONCLUSION: Prevalence and underdiagnosis of COPD in patients with IHD who undergo PCI are both high. These patients have an independent greater mortality and a higher number of cardiovascular events during follow-up