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Hypertension is one of the main cardiovascular risk factors. In the elderly, the most common form is isolated systolic hypertension, a consequence of the increase in arterial stiffness. None of the antihypertensives currently used affects arterial stiffness, whereas nitrates seem to have an effect. The aim of this work was to assess their effect on elderly patients with uncontrolled isolated systolic hypertension, defined as systolic blood pressure over 140 mmHg and diastolic blood pressure under 90 mmHg. The present study is a phase III, randomized, multicenter, double-blind, placebo-controlled clinical trial, conducted at the University Hospital La Princesa in Madrid. Patients of both sexes, aged 65 years or older, with poorly controlled isolated systolic hypertension, were treated with 40-60 mg of sustained-release isosorbide mononitrate or matching placebo for 12 weeks. The main objective was to assess the effect on clinical pulse pressure (PP); in addition, its effect on vascular function was evaluated. Analysis was performed by intention to treat. The study was registered at the European Union Clinical Trials Register (EUDRACT 2012-002988-10) and was funded by the Spanish Ministry of Health. A total of 58 patients with an average age of 77 years were enrolled, 32 were treated with nitrate, and 26 with placebo. No significant differences were found either in PP decline (5.28 vs 7.49 mmHg, p = 0.79) or in other variables, including parameters of vascular function. There were no differences in adverse events. The results of this study have not confirmed the benefit of nitrate treatment in isolated systolic hypertension or the improvement of vascular function.

Objective To identify factors associated with poor anticoagulation control with vitamin K antagonists (VKA) among outpatients with nonvalvular atrial fibrillation (NVAF) attended in Neurology and Internal Medicine in Spain. Methods Cross-sectional and multicenter study, from the ALADIN database, of outpatients with NVAF treated with VKA and attended in Internal Medicine and Neurology in Spain. Rates of anticoagulation control were determined with the direct and Rosendaal methods, considering data from the 6 months before the inclusion. Results Out of 1337 patients included in the ALADIN study, 750 were taking VKA, and complete information about INR values in the last 6 months was available in 383 patients. Mean scores of Charlson Index, CHADS2, CHA2DS2-VASc and HAS-BLED were 1.94 ± 1.54; 3.10 ± 1.26; 4.63 ± 1.54, and 2.20 ± 0.90, respectively. 46.2% and 47.0% of patients had an adequate anticoagulation control according to the direct and Rosendaal methods, respectively. Inadequate anticoagulation control according to the direct method was associated with diabetes (OR: 2.511; 95% CI: 1.144–5.659), prior labile INR (OR: 35.371; 95% CI: 15.058–83.083) and the determination of >6 INR controls in the last 6 months (OR: 4.747; 95% CI: 2.094–10.759), and according to the Rosendaal method, with prior labile INR (p Conclusions Despite the high thromboembolic risk, only a little more than a half of patients were well controlled. Factors associated with poor anticoagulation control were diabetes, labile INR, >6 INR controls and HAS-BLED.

Resumen Objetivo Identificar los factores asociados con el mal control de la anticoagulacion con antagonistas de la vitamina K (AVK) en pacientes con fibrilacion auricular no valvular (FANV) atendidos en consultas de Neurologia y Medicina Interna de Espana. Metodos Estudio transversal, multicentrico, anidado en el estudio ALADIN, de sujetos con FANV, tratados con AVK, atendidos en consultas de Medicina Interna o Neurologia de Espana. El grado de control de la anticoagulacion se estudio mediante el metodo directo y el de Rosendaal, considerando los 6 meses previos a la inclusion. Resultados De los 1.337 pacientes incluidos en ALADIN, 750 estaban tratados con AVK, con informacion completa sobre el INR de los ultimos 6 meses en 383 pacientes. Las puntuaciones medias del indice de Charlson, CHADS2, CHA2DS2-VASc y HAS-BLED fueron 1,94 ± 1,54; 3,10 ± 1,26; 4,63 ± 1,54 y 2,20 ± 0,90, respectivamente. El 46,2% y el 47,0% de los pacientes presentaban un control adecuado de la anticoagulacion por los metodos directo y Rosendaal, respectivamente. El control inadecuado de la anticoagulacion se asocio por el metodo directo con diabetes (OR: 2,511; IC 95%: 1,144-5,659), antecedentes de INR inestable (OR: 35,371; IC 95%: 15,058-83,083) y la realizacion de > 6 controles en los ultimos 6 meses (OR: 4,747; IC 95%: 2,094-10,759), y por el metodo de Rosendaal, con los antecedentes de INR inestable (p Conclusiones Pese al alto riesgo tromboembolico, solo estaban bien controlados algo mas de la mitad. Los factores asociados al mal control de la anticoagulacion fueron la diabetes, INR inestable, > 6 controles de INR y el HAS-BLED.

Familial hypercholesterolemia is an autosomal dominant disease of lipid metabolism caused by defects in the genes LDLR, APOB, and PCSK9. The prevalence of heterozygous familial hypercholesterolemia (HeFH) is estimated between 1/200 and 1/250. Early detection of patients with FH allows initiation of treatment, thus reducing the risk of coronary heart disease. In this study, we performed in vitro characterization of new LDLR variants found in our patients. Genetic analysis was performed by Next Generation Sequencing using a customized panel of 198 genes in DNA samples of 516 subjects with a clinical diagnosis of probable or definitive FH. All new LDLR variants found in our patients were functionally validated in CHO-ldlA7 cells. The LDLR activity was measured by flow cytometry and LDLR expression was detected by immunofluorescence. Seven new variants at LDLR were tested: c.518 G>C;p.(Cys173Ser), c.[684 G>T;694 G>T];p.[Glu228Asp;Ala232Ser], c.926C>A;p.(Pro309His), c.1261A>G;p.(Ser421Gly), c.1594T>A;p.(Tyr532Asn), and c.2138delC;p.(Thr713Lysfs*17). We classified all variants as pathogenic except p.(Ser421Gly) and p.(Ala232Ser). The functional in vitro characterization of rare variants at the LDLR is a useful tool to classify the new variants. This approach allows us to confirm the genetic diagnosis of FH, avoiding the classification as "uncertain significant variants", and therefore, carry out cascade family screening.

Aim: To analyze the use of oral anticoagulants in elderly patients with atrial fibrillation in clinical practice. Patients & methods: Cross-sectional and multicenter study performed in atrial fibrillation patients ≥75 years treated with oral anticoagulants ≥3 months. Results: 837 patients (83.0 ± 5.0 years; CHA 2 DS 2 -VASc 5.0 ± 1.4; HAS-BLED 2.1 ± 0.9; 70.8% vitamin K antagonists; 29.2% direct oral anticoagulants [DOACs]) were included. Poor adherence was observed in 27.9% of patients. Higher scores in the Pfeiffer’s test and FRAIL scale were associated with poorer adherence. Among patients treated with DOACs, 62.3% received the lower doses. Having high CHADS 2 score and being older were associated with the use of low doses. Conclusion: 28% of patients had a poor adherence to anticoagulant treatment. 62% of patients were treated with the lower doses of DOACs.

Background: Serum beta 2-microglobulin (B2M) levels have been found to be increased in patients with peripheral arterial disease (PAD), yet it is still unknown whether B2M correlates with PAD intensity. Objectives: We aim to evaluate the correlation between B2M and the ankle-brachial index (ABI) values in high-vascular-risk patients. Methods: This is a cross-sectional study of 63 high-vascular-risk patients admitted to the Cardiology Department or evaluated as outpatients in the Internal Medicine Department of our institution. Patients were classified into two groups according to their ABI: patients without PAD (n = 44, ABI values between 0.9 and 1.4) and patients with PAD (n = 19, ABI values lower than 0.9 or higher than 1.4). We performed univariate and multivariate analysis based on a multiple linear regression model. Results: Serum B2M levels were higher in patients with pathological ABI values than in those without PAD (2.36 ± 1.13 vs. 1.80 ± 0.65 mg/L; P

Atherothrombosis is one of the main causes of death worldwide. In Spain, as in other countries, this disease is a major public health problem, constituting a healthcare priority. The aim of the REduction of Atherothrombosis for Continued Health (REACH) registry is to analyze the long-term risk of atherothrombotic episodes in the at-risk population, evaluate the importance of cross risk, and define the prognostic factors of atherothrombotic episodes. More than 68,000 patients in more than 5,000 centers in 44 countries have been included in the REACH registry, of which 2,252 live in Spain. As observed internationally, in Spanish patients the complication rate at only 1-year of follow-up was high. The annual overall mortality rate in patients with established vascular disease or under primary prevention but with high atherothrombotic risk, represented by patients with risk factors only, was 3.57% and 1.98%, respectively, while that of cardiovascular mortality was 2.69% and 0.62%. In the subgroups of coronary artery disease (CAD), cerebral vascular disease (CVD) and peripheral artery disease (PAD) rates according to the affected territory were 3.47%, 2.78% and 1.46%, respectively. Involvement of more than one territory was clearly a poor prognostic factor: the annual complications rate increased according to whether 0, 1, 2, or 3 vascular beds were diseased for cardiovascular mortality (0.62%, 2.46%, 3.55% and 4.32%, respectively, p

Resumen La aterotrombosis es una enfermedad sistemica que puede expresarse por la afectacion de diferentes territorios vasculares, siendo mas frecuentemente el coronario, vasculocerebral o el arterial periferico el que lleva a su diagnostico. La ateromatosis aortica o de sus ramas puede ser asintomatica o manifestarse clinicamente en forma de isquemia mesenterica o nefropatia isquemica. Es, por ello, una patologia que afecta a diferentes especialidades medicas y ambitos asistenciales, como la cardiologia, la neurologia, la nefrologia, la endocrinologia, la cirugia vascular, la medicina interna y la atencion primaria. La afectacion simultanea de diferentes territorios, de forma sintomatica o asintomatica, hace necesario un abordaje global, multidisciplinar y coordinado. Adicionalmente, la actuacion medica no debe limitarse al tratamiento del accidente agudo, y el pilar clave lo constituye la prevencion, tanto primaria como secundaria. Es aqui donde, especialmente, las especialidades con vision global, como la medicina interna o los medicos de atencion primaria, deben tener un papel coordinador y prioritario. Esta intervencion multidisciplinar afecta no solamente al personal facultativo, sino tambien a otro tipo de personal sanitario, como dietistas, especialistas en ejercicio fisico y, muy especialmente, a la enfermeria, que debe desempenar un papel clave en el control de los factores de riesgo, en la educacion sanitaria y en la monitorizacion de adherencia al tratamiento.

Background: Isolated systolic hypertension is a highly prevalent disease among the elderly. The little available evidence on the efficacy of nitrates for treating the disease is based on small experimental studies. Methods/design: We performed a multicenter, randomized, double-blind, phase III, placebo-controlled trial in 154 patients aged over 65 years with refractory isolated systolic hypertension. Patients were randomized to placebo or 40 mg/day of extended-release isosorbide mononitrate added to standard therapy and titrated to 60 mg/day at week 6 if blood pressure exceeded 140/90 mmHg. The primary objective was to assess the effect on clinical pulse pressure of extended-release isosorbide mononitrate added to standard therapy in patients aged over 65 years with refractory isolated systolic hypertension after 3 months of treatment. The secondary objectives were as follows: to quantify the effect of adding the study drug on central blood pressure and vascular compliance using the augmentation index and pulse wave velocity; to evaluate the safety profile by recording adverse effects (frequency, type, severity) and the percentage of patients who had to withdraw from the trial because of adverse events; to quantify the percentage of patients who reach a clinical systolic blood pressure, Funding for the trial was provided by the Ministry of Health, Social Services and Equality (call for the development of independent clinical research, Exp Nº EC11-111)

Atherothrombosis is one of the main causes of death worldwide. In Spain, as in other countries, this disease is a major public health problem, constituting a healthcare priority. The aim of the REduction of Atherothrombosis for Continued Health (REACH) registry is to analyze the long-term risk of atherothrombotic episodes in the at-risk population, evaluate the importance of cross risk, and define the prognostic factors of atherothrombotic episodes. More than 68,000 patients in more than 5,000 centers in 44 countries have been included in the REACH registry, of which 2,252 live in Spain. As observed internationally, in Spanish patients the complication rate at only 1-year of follow-up was high. The annual overall mortality rate in patients with established vascular disease or under primary prevention but with high atherothrombotic risk, represented by patients with risk factors only, was 3.57% and 1.98%, respectively, while that of cardiovascular mortality was 2.69% and 0.62%. In the subgroups of coronary artery disease (CAD), cerebral vascular disease (CVD) and peripheral artery disease (PAD) rates according to the affected territory were 3.47%, 2.78% and 1.46%, respectively. Involvement of more than one territory was clearly a poor prognostic factor: the annual complications rate increased according to whether 0, 1, 2, or 3 vascular beds were diseased for cardiovascular mortality (0.62%, 2.46%, 3.55% and 4.32%, respectively, p0.05) and for cardiovascular mortality, plus myocardial infarction, plus stroke, plus hospitalization for cardiovascular reasons these rates were 5.50%, 4.18%, 20.59% and 19.40%. Importantly, these patients have a poor prognosis even in the short-term, especially those with established vascular disease; furthermore, the greater the number of diseased vascular beds, the poorer the prognosis. This situation must therefore be improved by earlier identification of at-risk individuals and by optimizing both primary and secondary preventive measures.

We report a patient with inappropriate secretion of thyrotropin (TSH) and a pituitary mass. Although she had been treated for biochemical hyperthyroidism with thyroid surgery and radioiodine ablation, she had never complained of specific symptoms or demonstrated signs of overt thyroid dysfunction. On evaluation, she had increased free thyroxine and TSH levels, normal serum glycoprotein alpha-subunit levels, and a significant TSH over-response to exogenous thyrotropin-releasing hormone stimulation. Magnetic resonance imaging with gadolinium enhancement showed a pituitary enlargement with suprasellar extension. An indium In 111 pentetreotide scan showed an abnormal focus of radionuclide accumulation in the pituitary area. Sequencing of the TRbeta gene showed that the patient was heterozygous for a new single nucleotide substitution resulting in the replacement of the normal arginine with a serine at amino acid 320 (R320S). We review the difficulties encountered in establishing a correct diagnosis in patients with inappropriate secretion of TSH in combination with pituitary enlargement. Due to its possible false-negative results, we do not recommend the use of indium In 111 pentetreotide as a tool in the differential diagnosis of inappropriate secretion of TSH.

Aim To assess the agreement between the clinical information provided by the ambulatory daytime average and 24 h average blood pressure value for diagnosing hypertension and assessing the effects of antihypertensive treatment. Methods We analysed 261 24 h amublatory monitoring records (SpaceLabs 90207, SpaceLabs, Redmond, Washington, USA) obtained from hypertensives over 18 years of age (mean age 55.8 years) in order to make a diagnosis of hypertension or assess its control in response to treatment. Recording was programmed to occur every 20 min during waking periods and every 30 min during sleep, daily activity also being registered. The criteria compared in the diagnosis of hypertension were: (1) the evaluation criterion: an average blood pressure for the activity period of less than 135/85 mmHg (Joint National Committee VI); (2) the gold standard: an average blood pressure over 24 h of less than 125/80 mmHg (World Health Organization–International Society of Hypertension, 1999). Results In 90% of the records, there was agreement between both criteria. In 7.2%, the awake blood pressure average was normal and the 24 h average high. Values obtained were: sensitivity, 89% (95% confidence interval 84–89%); specificity, 92% (95% CI 88–95%); positive predictive value, 95.6% (95% CI 93–98%); negative predictive value, 81% (95% CI 75–85%); pretest probability, 66% (95% CI 60–72%); positive likelihood ratio, 11; and negative likelihood ratio, 0.3. There were no significant differences in age, gender or percentage of treated subjects between the groups with and without agreement. Conclusions Daytime and 24 h average blood pressure may indeed carry similar information for diagnosing hypertension and assessing the effects of antihypertensive treatment in clinical practice. Ambulatory blood pressure monitoring used only during the daytime period could be better tolerated and agreed to by patients than 24 h monitoring.