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Mutations in APOB are the second most frequent cause of familial hypercholesterolemia (FH). APOB is highly polymorphic, and many variants are benign or of uncertain significance, so functional analysis is necessary to ascertain their pathogenicity. Our aim was to identify and characterize APOB variants in patients with hypercholesterolemia. Index patients (n = 825) with clinically suspected FH were analyzed using next-generation sequencing. In total, 40% of the patients presented a variant in LDLR, APOB, PCSK9 or LDLRAP1, with 12% of the variants in APOB. These variants showed frequencies in the general population lower than 0.5% and were classified as damaging and/or probably damaging by 3 or more predictors of pathogenicity. The variants c.10030A>G;p.(Lys3344Glu) and c.11401T>A;p.(Ser3801Thr) were characterized. The p.(Lys3344Glu) variant co-segregated with high low-density lipoprotein (LDL)-cholesterol in 2 families studied. LDL isolated from apoB p.(Lys3344Glu) heterozygous patients showed reduced ability to compete with fluorescently-labelled LDL for cellular binding and uptake compared with control LDL and was markedly deficient in supporting U937 cell proliferation. LDL that was carrying apoB p.(Ser3801Thr) was not defective in competing with control LDL for cellular binding and uptake. We conclude that the apoB p.(Lys3344Glu) variant is defective in the interaction with the LDL receptor and is causative of FH, whereas the apoB p.(Ser3801Thr) variant is benign.

The reduction of low-density lipoprotein cholesterol with lipid lowering therapy has demonstrated to decrease the risk of developing cardiovascular complications during the follow-up in primary and secondary prevention. Unfortunately, a great number of patients do not achieve recommended targets. This is mainly due to an insufficient use of the lipid-lowering therapy currently available. Although healthy life style changes are the basis of the treatment, in many cases this is not enough and it is necessary to add lipid lowering drugs to attain these targets. For these reasons, the current consensus document of the Spanish Society of Cardiology proposes 4 simple and feasible decision-making algorithms according to cardiovascular risk, with the aim of attaining cholesterol goals in the majority of primary prevention patients in a rapid an efficient way.

Resumen La reduccion del colesterol unido a lipoproteinas de baja densidad con el tratamiento hipolipidemiante ha demostrado disminuir el riesgo de presentar complicaciones cardiovasculares durante el seguimiento, tanto en prevencion primaria como secundaria. Desafortunadamente, un gran numero de pacientes no logran los objetivos de control recomendados. Esto se debe principalmente a un uso insuficiente de las terapias hipolipidemiantes actualmente disponibles. Aunque la base del tratamiento lo constituyen los cambios hacia un estilo de vida mas saludable, en numerosas ocasiones esto no es suficiente y es necesario anadir un tratamiento hipolipidemiante para alcanzar estos objetivos. Por estos motivos, en el presente documento de consenso de la Sociedad Espanola de Cardiologia se proponen 4 algoritmos de abordaje en funcion del riesgo cardiovascular de los pacientes, sencillos y facilmente aplicables, con el objetivo de lograr que la mayoria de los pacientes en prevencion primaria cumplan los objetivos de control de colesterol de manera rapida y eficiente.

Introduction and objectives Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin. This protein is polymorphic, with 3 isomorphs prevalent in the population. The carriers of the Hp2-2 isoform have a lower antioxidant capacity and, in the population with diabetes, an increased risk of subclinical vascular disease and cardiovascular complications. The objective of this study was to evaluate whether this isomorphy is associated with an increased risk of carotid arteriosclerosis in subjects with and without diabetes, and free of cardiovascular disease. Patients and methods A study was conducted in a population between 45 and 74 years of age, randomly selected from the northwest area of Madrid. The participants were characterised in terms of their glycaemic status by oral glucose overload and the determination of the concentration of Hb1Ac. The haptoglobin phenotypes in all of them were determined by means of an immunoenzymatic assay, and the presence of carotid arteriosclerosis by ultrasound. Results Of the 1256 participants included in the present analysis (mean age 61.6 ± 6 years, 41.8% males), the distribution of the isoforms of haptoglobin was as follows: Hp1-1: 13.3%, Hp1-2: 48.5%, and Hp2-2: 38.2%. In comparison with subjects Hp1-1 and Hp1-2, those with the Hp2-2 phenotype had a higher prevalence of dyslipidaemia (53.3% vs 43%; p Conclusion Subjects with the Hp2-2 phenotype of haptoglobin have a higher prevalence of carotid arteriosclerosis, which is independent of the presence of other cardiovascular risk factors and their glycaemic status.

Resumen Introduccion y objetivos La haptoglobina es una proteina implicada en la proteccion frente al dano oxidativo producido por el hierro de la hemoglobina. Esta proteina es polimorfica, con 3 isomorfas prevalentes en la poblacion. Los portadores de la isoforma Hp2-2 tienen una menor capacidad antioxidante, y en la poblacion con diabetes, un mayor riesgo de enfermedad vascular subclinica y de complicaciones cardiovasculares. Nuestro objetivo fue evaluar si dicha isomorfa se asocia con un mayor riesgo de arteriosclerosis carotidea en sujetos con y sin diabetes, libres de enfermedad cardiovascular. Pacientes y metodos Estudio realizado en una poblacion de entre 45 y 74 anos de edad seleccionada aleatoriamente del area noroeste de Madrid. Los participantes fueron caracterizados en cuanto a su estatus glucemico mediante una sobrecarga oral de glucosa y la determinacion de la concentracion de Hb1Ac. A todos ellos se les determino el fenotipo de la haptoglobina mediante un ensayo inmunoenzimatico y la presencia de arteriosclerosis carotidea mediante ecografia. Resultados De los 1.256 participantes incluidos en el presente analisis (edad media 61,6 ± 6 anos, 41,8% varones), la distribucion de las isoformas de la haptoglobina fue la siguiente: Hp1-1: 13,3%, Hp1-2: 48,5% y Hp2-2: 38,2%. En comparacion con los sujetos Hp1-1 y Hp1-2, aquellos con el fenotipo Hp2-2 tuvieron una mayor prevalencia de dislipemia (53,3% vs 43%, p Conclusion Los sujetos con el fenotipo Hp2-2 de la haptoglobina tienen una mayor prevalencia de arteriosclerosis carotidea, que es independiente de la presencia de otros factores de riesgo cardiovascular y de su estatus glucemico.

Few studies have analyzed the relationship between glucose variability (GV) and adverse health outcomes in patients with differences in glycemic status. The present study tests the hypothesis that GV predicts all-cause mortality regardless of glycemic status after simple adjustment (age and sex) and full adjustment (age, sex, cardiovascular disease, hypertension, use of aspirin, statins, GLP-1 receptor agonists, SGLT-2 inhibitors and DPP-4 inhibitors, baseline FPG and average HbA1c). Methods Prospective cohort study with 795 normoglycemic patients, 233 patients with prediabetes, and 4,102 patients with type 2 diabetes. GV was measured using the coefficient of variation of fasting plasma glucose (CV-FPG) over 12 years of follow-up. The outcome measure was all-cause mortality. Results A total of 1,223 patients (657 men, 566 women) died after a median of 9.8 years of followup, with an all-cause mortality rate of 23.35/1,000 person-years. In prediabetes or T2DM patients, the fourth quartile of CV-FPG exerted a significant effect on all-cause mortality after simple and full adjustment. A sensitivity analysis excluding participants who died during the first year of follow-up revealed the following results for the highest quartile in the fully adjusted model: overall, HR (95%CI) = 1.54 (1.26–1.89); dysglycemia (prediabetes and T2DM), HR = 1.41 (1.15–1.73); T2DM, HR = 1.36 (1.10–1.67). Conclusion We found CV-FPG to be useful for measurement of GV. It could also be used for the prognostic stratification of patients with dysglycemia, This study was funded by Instituto de Salud Carlos III through projects “PI15/00259” and “PI18/01025” and co-funded by the European Regional Development Fund,“A way of shaping Europe”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Cardiovascular (CV) polypills are a useful baseline treatment to prevent CV diseases by combining different drug classes in a single pill to simultaneously target more than one risk factor. The aim of the present trial was to determine whether the treatment with the CNIC-polypill was at least non-inferior to usual care in terms of low-density lipoprotein cholesterol (LDL-c) and systolic BP (SBP) values in subjects at high or very high risk without a previous CV event.The VULCANO was an international, multicentre open-label trial involving 492 participants recruited from hospital clinics or primary care centres. Patients were randomised to the CNIC-polypill -containing aspirin, atorvastatin, and ramipril- or usual care. The primary outcome was the comparison of the mean change in LDL-c and SBP values after 16 weeks of treatment between treatment groups.The upper confidence limit of the mean change in LDL-c between treatments was below the prespecified margin (10 mg/dL) and above zero, and non-inferiority and superiority of the CNIC-polypill (p = 0.0001) was reached. There were no significant differences in SBP between groups. However, the upper confidence limit crossed the prespecified non-inferiority margin of 3 mm Hg. Significant differences favoured the CNIC-polypill in reducing total cholesterol (p = 0.0004) and non-high-density lipoprotein cholesterol levels (p = 0.0017). There were no reports of major bleeding episodes. The frequency of non-serious gastrointestinal disorders was more frequent in the CNIC-polypill arm.The switch from conventional treatment to the CNIC-polypill approach was safe and appears a reasonable strategy to control risk factors and prevent CVD. Trial registration This trial was registered in the EU Clinical Trials Register (EudraCT) the 20th February 2017 (register number 2016-004015-13; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2016-004015-13 ).

Objetivo: El objetivo de este estudio fue analizar la relación entre el colesterol-HDL y el riesgo de infección por SARS-CoV-2 en mayores de 75 años residentes en la Comunidad de Madrid. Métodos: Estudio de una cohorte de base poblacional, compuesto por todos los residentes en Madrid (España) nacidos antes del 1 de enero de 1945 y vivos el 31 de diciembre de 2019. Los datos demográficos, clínicos y analíticos se obtuvieron de las historias clínicas electrónicas de atención primaria desde enero de 2015. La infección confirmada por SARS-CoV-2 se definió como un resultado positivo en la RT-PCR o en la prueba de antígeno. Los datos sobre infección por SARS-CoV-2 corresponden al periodo del 1 de marzo de 2020 hasta el 31 de diciembre de 2020. Resultados: De los 593.342 participantes de la cohorte, 501.813 tenían al menos una determinación de colesterol-HDL en los últimos 5 años. Su edad media era 83,4 ± 5,6 años y el 62,4% eran mujeres. Un total de 36.996 (7,4%) tuvieron una infección confirmada por SARS-CoV2 durante el año 2020. El riesgo de infección [odds ratio (intervalo de confianza 95%)] por SARS-CoV2 según los quintiles crecientes de colesterol-HDL fue de 1, 0,960 (0,915-1,007), 0,891 (0,848-0,935), 0,865 (0,824-0,909) y 0,833 (0.792-0,876), tras ajustar por edad, sexo, factores de riesgo cardiovascular y comorbilidades. Conclusiones: Existe una relación inversa y dosis-dependiente entre la concentración de colesterol-HDL y el riesgo de infección por SARS-CoV2 en los mayores de 75 años de la Comunidad de Madrid.

Pooled data from randomized clinical trials on lipid-lowering therapy have provided valuable information and clinical insights. Although cardiovascular disease is a common cause of death, mortality data have rarely been prominent in key lipid trials. The 4S, LIPID and HPS trials were the first to demonstrate a reduction in overall mortality. Lower- versus higher-intensity statin trials and non-statin lipid-lowering trials with ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors proved that additional lipid lowering significantly reduces the occurrence of cardiovascular events. However, only the ODYSSEY OUTCOMES trial showed a reduction in all-cause mortality. The aim of the present narrative review was to contrast these results with those of other key lipid trials: those assessing statins compared with placebo, those evaluating intensive- versus moderate-intensity lipid-lowering therapy and, finally, those investigating non-statin lipid-lowering therapies.

Highlights • Older patients with COVID infection have a similar clinical course than younger subjects. • Males have a greater COVID mortality than females. • Worsening dyspnea and decline renal function during admission associate with death. • Treatment with RAAS inhibitors associates with a greater survival., Introduction Older subjects have a higher risk of COVID-19 infection and a greater mortality. However, there is a lack of studies evaluating the characteristics of this infection at advanced age. Patients and methods We studied 404 patients ≥ 75 years (mean age 85.2 ± 5.3 years, 55 % males), with PCR-confirmed COVID-19 infection, attended in two hospitals in Madrid (Spain). Patients were followed-up until they were discharged from the hospital or until death. Results Symptoms started 2–7 days before admission, and consisted of fever (64 %), cough (59 %), and dyspnea (57 %). A total of 145 patients (35.9 %) died a median of 9 days after hospitalization. In logistic regression analysis, predictive factors of death were age (OR 1.086; 1.015–1.161 per year, p = 0.016), heart rate (1.040; 1.018–1.061 per beat, p

Aims The objective of the present study was to evaluate the prevalence of atrial fibrillation (AF) in nonagenarians living in the Community of Madrid, their clinical features, the use of anticoagulant therapy and factors associated with its use. Methods This was a cross-sectional study of 59 423 individuals aged ≥90 years, living in the Community of Madrid on 31 December 2015. Clinical information was obtained from a database that includes information from electronic medical records collected by 3881 general practitioners in primary care. Results Some 16.95% of nonagenarians (n = 10 077) were diagnosed with atrial fibrillation. These individuals have a higher prevalence of classic risk factors and established cardiovascular disease, as well as higher comorbidity. Of these, 67.6% received anticoagulant therapy, 27.9% received antiplatelet agents and 7.2% received both treatments simultaneously. Of the participants administered anticoagulation, 11.6% received a direct oral anticoagulant. The use of anticoagulant therapy was associated with a younger age, the presence of heart failure or venous thromboembolism, the absence of hypertension, a higher Barthel Index score, a greater number of prescribed drugs, a higher body mass index and a lower Charlson Comorbidity Index score. Conclusions Nonagenarians with atrial fibrillation have a high risk of stroke; however, high comorbidity and functional impairment have limited the use of anticoagulant therapy. Geriatr Gerontol Int 2019; 19: 203-207.

Aims Nonagenarians are a fast growing segment of industrialized countries' populations. Despite a greater risk of cardiovascular disease, there are limited data about their use of preventive therapies and factors guiding decisions regarding their prescription. The aim of this study was to evaluate the prevalence of cardiovascular diseases and the patterns of use of cardiovascular treatments in subjects ≥90 years old. Methods Population-based, cross-sectional study, in all nonagenarians residing in the Community of Madrid (Spain). Data were obtained from their electronic clinical records in primary care. Results Data were available from 59,423 subjects (mean age 93.3 years, 74.2% female, 13.5% with dementia). Prevalence of cardiovascular disease was 24.1% (10.9% with coronary artery disease (CAD), 13.1% with cerebrovascular disease (CVD) and 2.7% with peripheral artery disease(PAD)). In primary prevention, the use of statins and antiplatelet agents was 21.9% and 26.7%, respectively. Of subjects with vascular disease 27.7% were receiving a combined preventive strategy (use of antithrombotics, plus statins, plus blood pressure below 140/90 mmHg). Factors favourably associated with a combined preventive strategy were: female sex (odds ratio (OR) 1.29; 95% confidence interval (CI): 1.11–1.49), being independent versus totally dependent (OR 1.94; 95% CI: 1.43–2.65), diabetes (OR 1.42; 95% CI: 1.20–1.68), and negatively, age (OR 0.87; 95% CI: 0.85–0.90), CVD versus CAD (OR 0.41; 95% CI: 0.35–0.47), PAD versus CAD (OR 0.23; 95% CI: 0.18–0.30), dementia (OR 0.61; 95% CI: 0.49–0.76) and nursing home residency (OR 0.73; 95% CI: 0.57–0.93). Conclusion Nonagenarians have a great burden of cardiovascular diseases and receive a great number of preventive therapies, even in primary prevention, despite their unproven efficacy at these ages.

Objective To evaluate whether there were any differences in the risk factor profile associated with either the intima-media thickness (IMT) or the presence of carotid plaques. Methods Cross-sectional study in 1475 subjects between 45 and 75 years, randomly selected from the population of the Northwest area of Madrid (Spain). They had a physical exam, blood analysis, and ultrasound measurement of the IMT and of the presence of plaques. Results Mean IMT was 0.725 ± 0.132 mm. Forty seven percent of the participants had carotid plaques. In multivariate analysis, factors directly associated with the IMT were, age (β 0.227, p Conclusion Factors associated with the IMT and the presence of plaques are similar, a finding that support a continuum between muscular layer hypertrophy and arteriosclerosis development.

Resumen Objetivo Evaluar si existen diferencias en el perfil de factores de riesgo asociados con el grosor intima-media (GIM) y la presencia de placas carotideas. Metodos Estudio transversal de base poblacional, en 1.475 sujetos de entre 45 y 75 anos de edad, seleccionados de forma aleatoria de los registros de Atencion Primaria del area noroeste de Madrid. Se les realizo una exploracion fisica, una analitica y se les determino el GIM en carotida comun y la presencia de placas mediante ecografia. Resultados El GIM medio de la poblacion fue de 0,725 ± 0,132 mm. El 47% presentaban placas carotideas. En el analisis multivariante, los factores relacionados con el GIM fueron: edad (β 0,227, p Conclusion Los factores de riesgo asociados con el GIM y la presencia de placas son similares, un dato que apoya el continuo entre la hipertrofia de la capa muscular y el desarrollo de arteriosclerosis.

The presence of erectile dysfunction (ED) could be a warning of vascular disease in different arterial territories.The aim of this study was to investigate the association between ED and the presence of atherosclerosis in 2 different vascular beds: carotid and lower limbs.A total of 614 volunteers between 45 and 74 years of age (mean age 61.0 years) were randomly selected from the general population. ED was assessed using the International Index of Erectile Function (IIEF-5). Ankle-brachial index (ABI) measurement and carotid atherosclerosis were evaluated by echo-Doppler.Mean carotid intima-media thickness (IMT), prevalence of carotid plaques, mean ABI, and prevalence of ABI0.9 were the main outcome measures.ED was present in 373 subjects (59.7%). Mean carotid IMT was significantly higher in men with ED (0.762 ± 0.151 mm vs 0.718 ± 0.114 mm, P.001). Also the global prevalence of carotid plaques was more frequent in men with ED (63.8% vs 44.8%, P.001), even after adjusting by age, cardiovascular risk factors, and ongoing treatment (P = .039). Both the IMT and the prevalence of carotid plaques increased significantly with ED severity (P trend .004 and.001, respectively). There were no significant differences between groups neither in mean ABI nor in the prevalence of subjects with ABI0.9. However, there was a trend to a lower ABI and a higher prevalence of ABI0.9 with increasing ED severity.In the general population, the presence of ED identifies subjects with higher atherosclerosis burden in carotid arteries but not in the lower extremities.

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.

Background and aims Autosomal recessive hypercholesterolemia (ARH) is a rare disorder caused by mutations in LDLRAP1, which impairs internalization of hepatic LDL receptor (LDLR). ARH patients respond relatively well to statins or the combination of statins and Ezetimibe, but scarce and variable data on treatment with PCSK9 inhibitors is available. We aimed to identify and characterize the defect in a hypercholesterolemic patient with premature cardiovascular disease and determine the response to lipid-lowering treatment. Methods and results Gene sequencing revealed a homozygous c.1A > G:p.? variant in LDLRAP1. Primary lymphocytes were isolated from the ARH patient, one control and two LDLR-defective subjects, one LDLR:p.(Cys352Ser) heterozygote and one LDLR:p.(Asn825Lys) homozygote. The patient had undetectable full-length ARH protein by Western blotting, but expressed a lower-than-normal molecular weight peptide. LDLR activity was measured by flow cytometry, which showed that LDL binding and uptake were reduced in lymphocytes from the ARH patient as compared to control lymphocytes, but were slightly higher than in those from the LDLR:p.(Cys352Ser) heterozygote. Despite the analogous internalization defect predicted in ARH and homozygous LDLR:p.(Asn825Lys) lymphocytes, LDL uptake was higher in the former than in the latter. LDL-cholesterol levels were markedly reduced by the successive therapy with Atorvastatin and Atorvastatin plus Ezetimibe, and the addition of Evolocumab biweekly decreased LDL-cholesterol by a further 39%. Conclusions The LDLRAP1:c.1A > G variant is associated with the appearance of an N-terminal truncated ARH protein and to reduced, although still significant, LDLR activity in lymphocytes. Residual LDLR activity may be relevant for the substantial response of the patient to Evolocumab.

The objective of the present study was to evaluate the prevalence of atrial fibrillation (AF) in nonagenarians living in the Community of Madrid, their clinical features, the use of anticoagulant therapy and factors associated with its use.This was a cross-sectional study of 59 423 individuals aged ≥90 years, living in the Community of Madrid on 31 December 2015. Clinical information was obtained from a database that includes information from electronic medical records collected by 3881 general practitioners in primary care.Some 16.95% of nonagenarians (n = 10 077) were diagnosed with atrial fibrillation. These individuals have a higher prevalence of classic risk factors and established cardiovascular disease, as well as higher comorbidity. Of these, 67.6% received anticoagulant therapy, 27.9% received antiplatelet agents and 7.2% received both treatments simultaneously. Of the participants administered anticoagulation, 11.6% received a direct oral anticoagulant. The use of anticoagulant therapy was associated with a younger age, the presence of heart failure or venous thromboembolism, the absence of hypertension, a higher Barthel Index score, a greater number of prescribed drugs, a higher body mass index and a lower Charlson Comorbidity Index score.Nonagenarians with atrial fibrillation have a high risk of stroke; however, high comorbidity and functional impairment have limited the use of anticoagulant therapy. Geriatr Gerontol Int 2019; 19: 203-207.

Survivors of cancer have a shorter survival in the long term partly due to the increase in cardiovascular diseases (CVD). Some chemotherapy drugs, thoracic and cranial radiotherapy and above all the transplantation of hematopoietic cells are associated with an increase in the incidence of cardiovascular events compared with general population. Some of these treatments favor the development of a metabolic syndrome that could be the intermediary between these treatments and the development of CVD. It is recommended for cancer survivors to promote healthy lifestyles and the strict control of cardiovascular risk factors.

PCSK9 is a protease, synthesized mainly in the liver, which promotes the hepatic degradation of the LDL receptor and consequently decreases LDL receptor density and clearance of LDL particles. Statins inhibit HMG-CoA-reductase activity, an enzyme that catalyses an important step in hepatic cholesterol biosynthesis. The decrease of the hepatic intracellular cholesterol pool produced by these drugs upregulates the activity of the SREBP2 transcription factor, which subsequently stimulates the expression of the LDL receptor gene, an effect that is followed by an increase in the serum concentration of PCSK9. This article aims to review the effects of different lipid-lowering drugs on plasma PCSK9 concentrations. Overall, statins increase blood PCSK9 levels, an effect that is enhanced by ezetimibe. In contrast, others drugs, such as fibrates and niacin, could decrease PCSK9 levels.

Resumen Introduccion y objetivos Los pacientes con enfermedad arterial periferica tienen un elevado riesgo de complicaciones cardiovasculares y muerte. Sin embargo, la utilizacion de tratamientos cardiovasculares preventivos y la consecucion de objetivos terapeuticos en esta poblacion es suboptima. No existen datos que permitan conocer cual es la tasa de utilizacion de este tipo de farmacos en nuestro pais. Metodos PERIFERICA es un estudio transversal, realizado de mayo a diciembre de 2009 en 440 consultas de atencion primaria, medicina interna, cardiologia, cirugia vascular, endocrinologia y nefrologia, repartidas por todo el territorio nacional. Se incluyo a pacientes de 45 o mas anos, con enfermedad arterial periferica y una analitica sanguinea realizada durante los ultimos 6 meses. Se excluyo a los sujetos con enfermedad coronaria o cerebrovascular. Se recogieron diversas variables clinicas, antropometricas y analiticas y el tratamiento recibido. Resultados Se incluyo a 4.087 pacientes (media de edad, 68 anos; el 74% varones). La prevalencia de diabetes (50%) e hipertension arterial (90%) era muy elevada. El 79% recibia tratamiento hipolipemiante (el 76%, estatinas); el 85,5%, antihipertensivo (el 66%, bloqueadores del sistema renina-angiotensina), y el 83%, antitromboticos (el 75%, antiagregantes y el 11%, anticoagulantes). Un 30% tenia el colesterol unido a lipoproteinas de baja densidad Conclusiones A pesar de que existe un elevado numero de pacientes con enfermedad arterial periferica que reciben tratamiento mediante farmacos con evidencias sobre la reduccion de complicaciones cardiovasculares, el porcentaje de dichos pacientes que alcanza objetivos terapeuticos es muy bajo.

Resumen Introduccion y objetivos Determinar la prevalencia de enfermedad arterial periferica mediante el indice tobillo-brazo y evaluar los factores de riesgo, clinicos y diagnosticos asociados. Metodos Estudio transversal realizado entre 2007 y 2009, con muestra aleatoria de 2.833 sujetos entre 25 y 79 anos representativa del area de salud de Don Benito (Badajoz). Se considero diagnostico de enfermedad arterial periferica un indice tobillo-brazo Resultados La prevalencia de enfermedad arterial periferica fue del 3,7% (intervalo de confianza del 95%, 3,0-4,5%); el 5,0% (3,9-6,3%) en varones y el 2,6% (1,8-3,5%) en mujeres (p = 0,001). Las prevalencias acumuladas a partir de 50, 60 y 70 anos fueron del 6,2, el 9,1 y el 13,1% respectivamente. La enfermedad era sintomatica en el 13,3% (6,8-19,8%) de los casos. Las recomendaciones actuales de cribado no detectaron al 29,6% de los enfermos asintomaticos. El uso del indice aumento el 32,7% los casos de riesgo coronario alto. Se hallo asociacion positiva de la enfermedad con edad, tabaquismo, hipercolesterolemia, sedentarismo, microalbuminuria y enfermedad cardiovascular, y negativa con el consumo de alcohol. Conclusiones El uso del indice tobillo-brazo es aconsejable para el diagnostico de esta enfermedad, dada la baja prevalencia de formas sintomaticas y su capacidad para cambiar el riesgo coronario estimado. Se deberia adaptar los grupos de cribado a la poblacion espanola. Tabaquismo e hipercolesterolemia son los principales factores de riesgo.

Background The R46L variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been related to lipid levels and cardiovascular disease. Objective To evaluate the influence of this polymorphism on subclinical vascular disease and erectile dysfunction (ED). Methods We analyzed the association of the PCSK9 rs11591147 single-nucleotide polymorphism with lipid levels, intima-media thickness (IMT), and the ankle-brachial index, in 1188 adults free of cardiovascular disease, randomly selected from the population. In 473 male participants, we also investigated its relationship with ED. The association of the R46L polymorphism with lipid levels was also assessed in 2 cohorts of 1103 prepuberal children and 830 adolescents. Results The prevalence of the T allele was 2.9% in adults. Low-density lipoprotein cholesterol (LDL-cholesterol) levels did not vary according to this polymorphism (134 ± 32 vs 134 ± 31 mg/dL, for the TT + GT vs GG carriers, respectively, P = .931). Despite equal LDL-cholesterol levels, adults carrying the T allele had a lower mean common carotid IMT (0.685 ± 0.09 vs 0.723 ± 0.127 mm; P = .035), a lower maximum common carotid IMT (0.819 ± 0.11 vs 0.865 ± 0.159 mm; P = .040), and, in males, a lower prevalence of ED (36.8% vs 61%: P = .036), than GG carriers. Prevalence of the T allele was 3.2% in both cohorts of children. They had lower levels of LDL-cholesterol than GG subjects (100 vs 109 mg/dL; P = .060, for prepuberal children, and 85 vs 99 mg/dL; P = .010 for adolescents). Conclusion In our population, an association between the PCSK9 R46L variant and LDL-cholesterol levels is observed in children. In adults, although its association with lipid levels is not evident, there is a significant relationship between the PCSK9 R46L variant and markers of subclinical atherosclerosis, including IMT and ED.

This international meeting discussed the management of physical health in patients with schizophrenia in several countries including France, Spain, Germany, the UK and Italy. Physical health parameters, including weight, blood pressure, blood glucose, lipids and standard biochemical assessments are measured in many patients at the first hospital consultation. These reveal physical disorders such as obesity, hypertension, dyslipidaemia, the metabolic syndrome, substance abuse, cardiovascular disease, extrapyramidal symptoms, sexual dysfunction and diabetes in substantial proportions of patients. Psychiatrists consider switching antipsychotic therapy if excessive sedation, extrapyramidal symptoms, unacceptable weight gain, hyperglycaemia or dyslipidaemia occur. In general, switching is more likely to be considered for symptomatic adverse events than for laboratory abnormalities. Switching is discouraged by limited knowledge of protocols, the absence of guidelines and fears of relapse or reduced treatment adherence. The physical health of patients with schizophrenia receives much less attention in the community setting than in the hospital setting. Improved guidelines, protocols, resources and support are needed to improve the physical health of patients in the community.

The protective role of HDL-cholesterol against atherosclerosis has been established in epidemiological and experimental studies. In spite of this, there are a few of clinical trials that have unequivocally demonstrated that raising HDL-cholesterol reduces the cardiovascular risk. In the present article we review the putative protective mechanisms associated with HDL particles, the evidence linking HDL-cholesterol increase with a reduction in cardiovascular risk as well as the pharmacological and non-pharmacological therapies for increasing HDL-cholesterol. Finally, we comment on experimental drugs currently under development, that elevate HDL-cholesterol.

Background and objective: To evaluate the factors associated with intima-media thickness (IMT) and carotid plaques in patients with familial hypercholesterolemia (FH) and to assess the evolution following 1 year of treatment. Patients and method: Subjects (n ¼ 201) diagnosed as having probable or definite FH according to the MED-PED criteria had a clinical history, physical examination, blood chemistry and lipid profile determined. Ultrasound was used to measure the IMT in both common carotid arteries and to assess the presence of plaques. The measurements were repeated in 123 of the patients after 1 year of treatment.

Women have a higher morbidity and mortality than men after an acute coronary event. We analyzed the prescription rates of evidence-based pharmacological therapies for patients with stable coronary heart disease and whether there were any differences with respect to gender.This cross-sectional study evaluated 8817 patients, 26.3% women, receiving attention from 1799 family doctors in primary care centers (PCC) throughout Spain, and who had had a coronary event requiring hospitalization in the previous 6 months to 10 years.Mean age was 65.4 years and a mean time-lapse since hospitalization of 37.4 months. In the overall population, prescription medications were: antiplatelet drugs in 80.5% of patients, 79% statins, 66% blockers of the angiotensin-renin system (BARS) and 47% beta-blockers. Males received less cardiovascular disease medications than females (4.3+/-1.5 versus 4.6+/-1.6, respectively; p0.001), but when adjusted for risk factors the significance was lost (p=0.231). Following adjustment for risk factors and for co-morbidities, the use of diuretics was significantly higher in women while beta-blockers and statins were higher in men. The triple combination of antithrombotics, beta-blockers and statins was used in 41.4% (43.8% males versus 34.6% females; p0.001) while 24.3% used this triple combination plus a BARS; without significant difference between the genders.An important percentage of patients with stable coronary disease, particularly women, attended-to in primary care do not receive medications that have been shown to decrease the morbido-mortality of cardiovascular disease.

Fundamento y objetivo Los pacientes con enfermedad arterial en varios territorios presentan una elevada tasa de complicaciones vasculares y de mortalidad. Su identificacion permitiria definir a un subgrupo de la poblacion de muy alto riesgo, candidatos a recibir medidas preventivas mas energicas. El objetivo del presente estudio ha sido estimar la prevalencia de enfermedad arterial periferica subclinica en personas con antecedentes de enfermedad vascular en otros territorios arteriales. Pacientes y metodo Se incluyo en el estudio a pacientes con historia de enfermedad coronaria y/o cerebrovascular entre los 3 meses y los 5 anos previos, atendidos en consultas de medicina interna repartidas por toda la geografia nacional. Se les realizaron anamnesis, exploracion fisica, analitica sanguinea y urinaria, y se les determino el indice tobillo-brazo (ITB). Resultados Se estudio a 1.203 pacientes (64% varones), con una edad media de 74,3 anos. El 55,4% tenia antecedentes de enfermedad coronaria, un 38% de enfermedad cerebrovascular y un 6,7% de afectacion en ambos territorios. La prevalencia de ITB bajo ( Conclusiones La prevalencia de un ITB bajo es elevada en pacientes asintomaticos con enfermedad coronaria o cerebrovascular, especialmente si presentan afectacion conjunta de ambos territorios.

Fundamento y objetivo: La presencia de insuficiencia renal cronica (IRC) aumenta el riesgo de enfermedad cardiovascular, especialmente en los pacientes con enfermedad coronaria. El objetivo de este estudio ha sido examinar la prevalencia de IRC oculta (IRCO) en pacientes con enfermedad coronaria estable e investigar los factores asociados a ella para favorecer su deteccion. Pacientes y metodo: Se ha realizado un estudio transversal en el que participaron 7.884 sujetos que habian ingresado por un episodio coronario entre 6 meses y 10 anos antes. Se calculo el filtrado glomerular segun la ecuacion abreviada del estudio Modification of Diet in Renal Disease (MDRD). Se considero IRC cuando el filtrado glomerular era menor de 60 ml/min/1,73 m2 e IRCO cuando ademas la creatinina serica era inferior a 133 mmol/l en varones y a 124 mmol/l en mujeres. Resultados: La edad media de la poblacion estudiada era 65,3 anos y el 73,7% eran varones. Presentaba IRC un 22,4%, de los que el 68,3% tenia cifras de creatinina normales. En los pacientes con IRCO la prevalencia de factores de riesgo y enfermedades cardiovasculares asociadas era intermedia entre aquellos sin IRC y entre los que presentaban IRC con creatinina elevada. La edad, el sexo femenino, la presencia de hipertension arterial, diabetes, insuficiencia cardiaca, enfermedad cerebrovascular y enfermedad arterial periferica se asociaron de manera significativa e independiente con la presencia de IRCO en el analisis multivariante. Conclusiones: Casi uno de cada 4 pacientes con enfermedad coronaria estable presenta IRC, la mayoria de ellos con creatinina normal, siendo especialmente frecuente en las mujeres y con el aumento de la edad.

La aterosclerosis es una enfermedad cronica, generalizada y progresiva que afecta sobre todo a las arterias de mediano tamano. Clinicamente se manifiesta como cardiopatia isquemica, enfermedad cerebrovascular o enfermedad arterial periferica (EAP). En nuestro pais es la causa de 124.000 muertes anuales. A pesar de la tendencia a la disminucion de la tasa ajustada por edad de la mortalidad por las enfermedades cardiovasculares, el impacto sanitario de estas se espera que aumente. Los factores de riesgo son los mismos para los distintos territories vasculares y se pueden clasificar como causales, condicionales o predisponentes. La presencia de aterosclerosis en un territorio vascular se asocia con frecuencia con la afectacion de otros territorios. Las tablas para la estimacion del riesgo, los marcadores de inflamacion, las pruebas de imagen y el indice tobillo-brazo pueden ser utiles para detectar la presencia de aterosclerosis subclinica. Dado que es una enfermedad sistemica, el tratamiento con estatinas, antiagregantes plaquetarios o inhibidores de la enzima de conversion de la angiotensina han demostrado consistentemente su beneficio, con independencia del lecho vascular afectado.

Atherosclerosis is a widespread, chronic progressive disease that mainly involves medium-sized arteries. Clinically, it can become apparent as ischemic heart disease, cerebrovascular disease, or peripheral arterial disease. In Spain, atherosclerosis is responsible for 124 000 deaths each year. Despite the trend towards a reduction in the aged-adjusted mortality rate for cardiovascular disease, the public health burden is expected to increase. The risk factors are the same for all affected vascular beds, regardless of location, and can be classified as either causal, conditional or predisposing. The presence of atherosclerosis in a particular vascular bed is frequently associated with disease in other vascular territories. Risk assessment tables, inflammatory markers, imaging, and the ankle-brachial index can help in identifying subclinical atherosclerosis. Given the systemic nature of the disease, treatment with statins, antiplatelet agents and angiotensin-converting enzyme inhibitors have consistently proven beneficial, irrespective of the vascular bed affected.

Survivors of cancer have a shorter survival in the long term partly due to the increase in cardiovascular diseases (CVD). Some chemotherapy drugs, thoracic and cranial radiotherapy and above all the transplantation of hematopoietic cells are associated with an increase in the incidence of cardiovascular events compared with general population. Some of these treatments favor the development of a metabolic syndrome that could be the intermediary between these treatments and the development of CVD. It is recommended for cancer survivors to promote healthy lifestyles and the strict control of cardiovascular risk factors.

To investigate some individual and genetic factors that may influence the response of low-density lipoprotein cholesterol (LDL-C) to pravastatin treatment, we recruited 440 subjects with hypercholesterolemia (mean age, 57 years; 43% men) from 21 primary health care centers-outpatient clinics into a prospective, multicentered intervention trial. Pravastatin (20 mg/d) was prescribed for 16 weeks. The main outcome was the percentage variation in LDL-C concentration relative to baseline. Blood analyses and genotyping were performed centrally. The results indicated that LDL-C decreased by 20.5% (range, +21% to -66%) after pravastatin treatment. Baseline concentration of LDL-C (the higher the concentration, the greater the decrease), lipoprotein (a) levels (the lower the concentration, the greater the response), and Ava II polymorphism of the LDL-receptor gene significantly influenced the hypolipemic effect ( P.001, P = .014, and P = .004, respectively). These 3 factors combined explained 10.6% of the variation in LDL-C response. Age, sex, smoking habit, alcohol consumption, body mass index, and apolipoprotein E genotype had no significant effect on response. We conclude that baseline levels of LDL-C and lipoprotein (a) together with the Ava II polymorphism of the LDL-receptor gene have a significant influence on the LDL-C response to pravastatin treatment in patients monitored in a standard primary health care outpatient clinic setting.

Fundamento y objetivo: La funcion de Framingham, recomendada por el National Cholesterol Education Program en su documento Adult Treatment Panel III (ATP-III) y las tablas de riesgo del Systematic Coronary Risk Evaluation (SCORE) son las funciones mas utilizadas para la estratificacion del riesgo cardiovascular, y ambas recomiendan intensificar las medidas higienicas y terapeuticas en las personas que presenten un riesgo alto. El objetivo del presente estudio fue comparar la estratificacion del riesgo obtenida con ambas clasificaciones en una poblacion de sujetos mayores de 60 anos. Sujetos y metodo: Se incluyo en el estudio a 1.001 personas no diabeticas de entre de 60 y 79 anos (media de 69 anos, un 67%, mujeres) sin evidencia de enfermedad vascular. Se clasifico a los participantes segun su riesgo fuera bajo, medio o alto de acuerdo con el ATP-III ( 20% de riesgo a los 10 anos, respectivamente) y el SCORE ( = 5% de riesgo a los 10 anos, respectivamente). Resultados: Un 11,7% de la poblacion se considero de riesgo alto segun la ecuacion de Framingham, frente a un 17,6% segun el SCORE. Unicamente un 5% de las mujeres fueron clasificadas de riesgo alto con cualquiera de las funciones, frente a un 16,7 y un 44,4% de los varones segun las tablas de Framingham y de SCORE, respectivamente. Los resultados fueron similares al dividir por grupos de edad. De acuerdo con las guias del SCORE, un 39% de los varones y un 20% de las mujeres eran candidatos a recibir tratamiento hipolipemiante. Conclusiones: En comparacion con la funcion de Framingham, la aplicacion del SCORE en varones mayores de 60 anos triplica el numero de sujetos de alto riesgo candidatos a medidas de prevencion energicas.

Low levels of high-density lipoprotein cholesterol (HDL-C) show a consistent relationship with the development of atherosclerosis. The underlying mechanisms are not well understood, but recent studies in subjects with primary hypoalphalipoproteinemia suggest that this could represent a proinflammatory condition. To better assess the link between HDL-C levels and C-reactive protein levels and the possible role of chronic infections as putative mediators of this relationship, we studied a population sample with nonselected causes of hypoalphalipoproteinemia. Eighty-six consecutive patients with HDL-C levels below 40 mg/dL who attend our lipid clinic and 86 control subjects with normal concentrations matched for gender, age, smoking habit, and weight were included in the study. Mean HDL-C levels were 34 ± 3.9 and 55.4 ± 8.8 mg/dL for subjects with hypoalphalipoproteinemia and control subjects, respectively. C-reactive protein concentrations were increased in case patients as compared with control subjects (2.13 ± 2.0 vs 1.52 ± 1.8 mg/L; P = .025). The prevalence of herpes simplex virus type 1, cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori infections did not differ between the 2 groups. Although a possible confounding variable could be a degree of insulin resistance within the group of patients with low HDL-C levels, our results indicate that C-reactive protein levels are increased in subjects with nonselected hypoalphalipoproteinemia and that chronic infections do not appear to mediate this relationship.

Statins decrease cardiovascular morbidity and mortality, essentially, by reducing LDL-cholesterol levels and, additionally, by increasing HDL-cholesterol concentrations. Environmental and genetic factors are known to affect LDL-C response to statins but less is known regarding HDL-C. We have evaluated the lipid and lipoprotein response to 20 mg/day of pravastatin for 16 weeks in relation to the G/A polymorphism in the promoter region of the apo A-I gene in 397 hypercholesterolaemic subjects followed-up on an out-patient basis. In the study population, 61.7% were homozygous for the G allele and 36% were heterozygous. The A allele carriers had an HDL-C 6.5% higher than the G allele homozygotes (P=0.021 in univariate analysis; P=0.009 in multivariate analysis). However, on segregation by gender and smoking status the effect was significant only in non-smoking males. The A allele carriers did not increase their HDL-C concentrations after treatment (-0.3, 95%CI -3.3 to 2.7%) while G allele homozygotes had a 4.9% increase (95%CI 2.5-7.3%). Differences in the response between both groups were significant before (P=0.008) and after adjustment for confounding variables such as age and baseline HDL-C concentration (P=0.046). We conclude that the G/A polymorphism of the apo A-I promoter region affects not only baseline HDL-C concentrations but also its response to pravastatin treatment.

Introduccion y objetivos A pesar de que se conoce el valor pronostico de varios marcadores de inflamacion en el sindrome coronario agudo sin elevacion del segmento ST (SCASEST), aun se ignora que subconjunto de estos proporciona mejor informacion y que grado de asociacion existe entre ellos. El objetivo del estudio SIESTA es establecer el valor pronostico de la proteina C reactiva, fibrinogeno, neopterina, interleucinas 6, 8, 10 y 18, factor de necrosis tumoral, e-selectina, endotelina 1, factor tisular, molecula de adhesion celular vascular-1 (VCAM-1) e intercelular-1 (ICAM-1), proteina plasmatica-A asociada al embarazo (PAPP-A), peptido natriuretico ventricular (tipo B), troponina I o T, leucocitos e isoforma MB de la creatinfosfocinasa (CK-MB), en pacientes con SCASEST. Pacientes y metodo SIESTA es un estudio prospectivo, multicentrico, que incluira a pacientes que hayan presentado dolor toracico sugestivo de sindrome coronario agudo en las ultimas 48 h y alguna de las siguientes condiciones: signos electrocardiograficos de isquemia miocardica, enfermedad vascular documentada o elevacion de la concentracion de troponinas. Se realizara un seguimiento clinico durante un ano, con determinaciones hematologicas y bioquimicas en el momento del ingreso, del alta, y a los 30, 180 y 365 dias. Se validaran las escalas TIMI (Thrombolysis In Myocardial Infarction) y PEPA (Proyecto de Estudio del Pronostico de la Angina). La variable principal estara compuesta de muerte por cualquier causa, muerte de origen cardiaco, infarto de miocardio no letal y angina inestable que requiera hospitalizacion o revascularizacion urgente. La evaluacion individual de cada una de las variables se considerara como objetivo secundario. Este estudio ofrecera valiosa informacion prospectiva acerca del valor pronostico de un importante numero de marcadores inflamatorios en pacientes de origen mediterraneo asistidos en la practica medica habitual.

OBJECTIVE: Combined hyperlipidaemia is a common and highly atherogenic lipid phenotype with multiple lipoprotein abnormalities that are difficult to normalise with single-drug therapy. The ATOMIX multicentre, controlled clinical trial compared the efficacy and safety of atorvastatin and bezafibrate in patients with diet-resistant combined hyperlipidaemia. PATIENTS AND STUDY DESIGN: Following a 6-week placebo run-in period, 138 patients received atorvastatin 10mg or bezafibrate 400mg once daily in a randomised, double-blind, placebo-controlled trial. To meet predefined low-density lipoprotein-cholesterol (LDL-C) target levels, atorvastatin dosages were increased to 20mg or 40mg once daily after 8 and 16 weeks, respectively. RESULTS: After 52 weeks, atorvastatin achieved greater reductions in LDL-C than bezafibrate (percentage decrease 35 vs 5; p < 0.0001), while bezafibrate achieved greater reductions in triglyceride than atorvastatin (percentage decrease 33 vs 21; p < 0.05) and greater increases in high-density lipoprotein-cholesterol (HDL-C) [percentage increase 28 vs 17; p < 0.01 ]. Target LDL-C levels (according to global risk) were attained in 62% of atorvastatin recipients and 6% of bezafibrate recipients, and triglyceride levels

88.450 La eficacia de diferentes medidas terapeuticas para prevenir un primer episodio cardiovascular y/o cerebrovascular ha sido puesta de manifiesto en diversos ensayos de intervencion. Asi, el tratamiento con antiagregantes, hipolipemiantes y antihipertensivos ha demostrado reducciones significativas en la morbimortalidad de origen vascular en prevencion primaria. Este hecho es aun mas llamativo si tenemos en consideracion que el beneficio de los hipolipemiantes ha sido demostrado en sujetos sin hipercolesterolemia y el de los antihipertensivos en personas con cifras tensionales normales. Sin embargo, dada la necesidad de racionalizar los recursos, la utilizacion de estos farmacos requiere la identificacion de aquellas personas cuyo riesgo de complicaciones vasculares sea lo suficientemente alto como para que el beneficio del tratamiento, en terminos de reduccion absoluta de riesgo, supere los inconvenientes derivados del numero potencial de efectos adversos y del coste economico de un tratamiento que, generalmente, debe ser mantenido durante toda la vida. El termino «factor de riesgo cardiovascular» fue introducido por primera vez a partir de las observaciones procedentes del seguimiento de la cohorte de Framingham en la decada de los cincuenta. Actualmente, la estimacion del riesgo cardiovascular global se sustenta en la utilizacion de formulas derivadas de este estudio, las cuales tienen en consideracion tanto el numero como la gravedad de los diferentes factores de riesgo alli identificados. A pesar de tratarse de un instrumento valioso, no identifica a la totalidad de los pacientes que presentan un primer episodio vascular. Ademas, su utilidad en otras poblaciones distintas de aquellas donde se han generado sobrevalora el riesgo cardiovascular si en la zona de aplicacion existe una baja incidencia de enfermedad coronaria, como es el caso de nuestro pais. Estos inconvenientes han conducido a la busqueda activa de nuevos marcadores que mejoren la prediccion del riesgo y, sobre todo, a la busqueda de nuevas tecnicas que permitan un diagnostico incruento de la enfermedad arterial, coronaria o cerebral asintomatica. Algunas de estas tecnicas, como la eco-Doppler de troncos supraaorticos (TSA) tienen un valor predictivo moderado y exigen un instrumental y entrenamiento que no facilitan su utilizacion generalizada. Otras estan actualmente en fase de investigacion. La resonancia magnetica (RM), la tomografia computarizada (TC) con haz de electrones o la TC helicoidal permiten una evaluacion directa del arbol coronario. Si bien el valor predictivo de estas tecnicas todavia no esta establecido, se puede estimar que son procedimientos costosos que permitiran evaluar el riesgo en determinados sujetos pero no serviran para realizar estrategias diagnosticas a grandes grupos de poblacion.

Journal Article; BACKGROUND Despite the progressive increase in life expectancy and the relationship between aging with multi-morbidities and the increased use of healthcare resources, current clinical practice guidelines (CPG) on cardiometabolic risk cannot be adequately applied to elderly subjects with multiple chronic conditions. Its management frequently becomes complicated by both, an excessive use of medications that may lead to overtreatment, drug interactions and increased toxicity, and errors in dosage and non-compliance. Concerned by this gap, the Spanish Society of Internal Medicine created a group of independent experts on cardiometabolic risk who discussed what they considered to be unanswered questions in the management of elderly patients. DISCUSSION Current guidelines do not specifically address the problem of elderly with multiple chronic conditions. For this reason, the combined use of the limited available evidence, clinical experience and common sense, could all help us to address this unmet need. In very old people, life expectancy and functionality are the most important factors for guiding potential treatments. Their higher propensity to develop serious adverse events and their shorter lifespan could prevent them from obtaining the potential benefits of the interventions administered. SUMMARY In this document, experts on cardiometabolic risk factors have established a number of consensual recommendations that have taken into account international guidelines and clinical experience, and have also considered the more effective use of healthcare resources. This document is intended to provide general recommendations for clinicians and to promote the effective use of procedures and medications. Yes

Background: The aim of our study was to evaluate whether pravastatin treatment affected biochemical markers of bone turnover. Methods: Thirty-six hypercholesterolemic post-menopausal women, not on hormonal replacement therapy, were selected from a population study evaluating factors affecting cholesterol response to pravastatin. After a 6-week period on a 30% fat diet, participants received treatment with 20 mg/day of pravastatin during a 16-week follow-up period. Pre- and post-treatment samples were analyzed for procollagen I aminoterminal peptide (PINP) and bone alkaline phosphatase (bAP) as markers of bone formation, carboxyterminal telopeptide of collagen I (CTX) as a marker of bone resorption, and procollagen III aminoterminal propeptide (PIIINP) as a marker of fibrogenesis. Results: Total cholesterol decreased from 7.26±0.83 to 6.1±0.77 mmol/l with pravastatin treatment. PINP levels significantly increased (from 33.6±13 to 37.4±16, p=0.03) without changes in bAP or CTX. Individual changes in PINP correlated with individual reduction in cholesterol levels (r=0.337, p=0.04). There was no significant change in PIIINP concentration. Conclusions: Pravastatin treatment increased PINP levels, a marker of bone formation, in hypercholesterolemic, post-menopausal women, without affecting bone resorption. PIIINP concentration, a marker of liver fibrogenesis, was not affected by the treatment.

Fundamento La apolipoproteina E (apo E) desempena un importante papel en el desarrollo de la arteriosclerosis. Esta proteina es polimorfica, habiendose descrito tres alelos codominantes, e2, e3 y e4. En el presente estudio hemos evaluado la asociacion entre el alelo e4 y la presencia de enfermedad coronaria en una muestra de sujetos hipercolesterolemicos procedentes de toda la geografia nacional. Sujetos y metodo Se seleccionaron 389 personas (un 56% de mujeres, con una edad media de 57 anos) con indicacion de tratamiento hipolipemiante tras seguir una dieta pobre en grasas saturadas. La concentracion de lipidos y lipoproteinas y la determinacion del genotipo de apo E fueron realizadas de forma centralizada. Resultados La distribucion por genotipos de la poblacion fue la siguiente: e2/e3, 3%; e3/e3, 75%; e3/e4, 20%; e4/e4, 1%, y e2/e4, 1%. Los sujetos fueron divididos segun poseian (n = 83) o no (n = 303) el alelo e4, siendo excluidos los e2/e4. No existieron diferencias entre ambos grupos en la edad, el sexo, la prevalencia de hipertension arterial o el tabaquismo, ni en la concentracion de lipidos. La prevalencia de enfermedad coronaria fue del 15,7% en los e4 y del 6,9% en los no e4 (OR, 2,49; IC del 95%, 1,19-5,22). En un analisis de regresion logistica multiple, la relacion entre el alelo e4 y la presencia de enfermedad coronaria se mantuvo significativa tras corregir para la edad, el sexo, los factores de riesgo cardiovascular y la concentracion de colesterol total, cHDL y trigliceridos (OR, 2,56; IC del 95%, 1,03-6,39). Conclusion En Espana, los portadores del alelo e4 presentan una prevalencia de enfermedad coronaria mayor que los no e4.