Jesús Millán Núñez-Cortés

Residual macrovascular risk in 2013: what have we learned?

Cardiovascular disease poses a major challenge for the 21st century, exacerbated by the pandemics of obesity, metabolic syndrome and type 2 diabetes. While best standards of care, including high-dose statins, can ameliorate the risk of vascular complications, patients remain at high risk of cardiovascular events. The Residual Risk Reduction Initiative (R3i) has previously highlighted atherogenic dyslipidaemia, defined as the imbalance between proatherogenic triglyceride-rich apolipoprotein B-containing-lipoproteins and antiatherogenic apolipoprotein A-I-lipoproteins (as in high-density lipoprotein, HDL), as an important modifiable contributor to lipid-related residual cardiovascular risk, especially in insulin-resistant conditions. As part of its mission to improve awareness and clinical management of atherogenic dyslipidaemia, the R3i has identified three key priorities for action: i) to improve recognition of atherogenic dyslipidaemia in patients at high cardiometabolic risk with or without diabetes; ii) to improve implementation and adherence to guideline-based therapies; and iii) to improve therapeutic strategies for managing atherogenic dyslipidaemia. The R3i believes that monitoring of non-HDL cholesterol provides a simple, practical tool for treatment decisions regarding the management of lipid-related residual cardiovascular risk. Addition of a fibrate, niacin (North and South America), omega-3 fatty acids or ezetimibe are all options for combination with a statin to further reduce non-HDL cholesterol, although lacking in hard evidence for cardiovascular outcome benefits. Several emerging treatments may offer promise. These include the next generation peroxisome proliferator-activated receptorα agonists, cholesteryl ester transfer protein inhibitors and monoclonal antibody therapy targeting proprotein convertase subtilisin/kexin type 9. However, long-term outcomes and safety data are clearly needed. In conclusion, the R3i believes that ongoing trials with these novel treatments may help to define the optimal management of atherogenic dyslipidaemia to reduce the clinical and socioeconomic burden of residual cardiovascular risk.

Dislipidemias: un reto pendiente en prevención cardiovascular. Documento de consenso CEIPC/SEA

In Spain, where cardiovascular disease (CVD) is the leading cause of death, hypercholesterolemia, one of the most prevalent risk factors in adults, is poorly controlled. Dyslipidemia should not be approached in isolation, but in the context of overall cardiovascular risk (CVR). Measurement of CVR facilitates decision making, but should not be the only tool nor should it take the place of clinical judgment, given the limitations of the available calculation methods. This document, prepared by the Interdisciplinary Spanish Committee on Cardiovascular Prevention, at the proposal of the Spanish Society of Arteriosclerosis, reviews the cardiovascular prevention activities of the regional health authorities, scientific societies and medical professionals. An initiation of a national strategy on cardiovascular prevention is proposed based on lifestyle modification (healthy diet, physical activity and smoking cessation) through actions in different settings. At the population level, regulation of food advertising, elimination of trans fats and reduction of added sugar are feasible and cost-effective interventions to help control dyslipidemias and reduce CVR. In the health setting, it is proposed to facilitate the application of guidelines, improve training for medical professionals, and include CVR assessment among the quality indicators. Scientific societies should collaborate with the health authorities and contribute to the generation and transmission of knowledge. Finally, it is in the hands of professionals to apply the concept of CVR, promote healthy lifestyles, and make efficient use of available pharmacological treatments.

Estudio REALIST (REsiduAl risk, LIpids and Standard Therapies): Un análisis del Riesgo Residual dependiente del perfil lipídico en el síndrome coronario agudo

The R3i Foundation (Residual Risk Reduction Initiative), an independent, multinational and academic organization, is conducting the REALIST (Residual Risk, Lipids and Standard Therapies) study in 40 centers in different countries. This is a retrospective epidemiological study, designed to provide new data on the residual risk of major coronary events attributable to lipid abnormalities in patients receiving the current standard treatment. The initial results are expected in mid 2010, and the overall results at the end of 2010.

Relationship between lipoprotein (a) and micro/macro complications in type 2 diabetes mellitus: a forgotten target

Objectives Increased lipoprotein (a) serum concentrations seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper insight into relationship between the plasma concentrations of lipoprotein (a) and the micro- and macro-vascular complications of type 2 diabetes mellitus and to identify possible differences in this association. Methods This is a descriptive observational cross-sectional study. Two-hundred and seventeen elderly patients with type 2 diabetes mellitus were included from the internal medicine outclinic. Anthropometric data, analytical data (insulin reserve, basal and postprandial peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical data as hypertension, obesity, micro- and macrovascular complications were collected. Results Patients were grouped according to the type 2 diabetes mellitus time of evolution. The mean plasma concentration of lipoprotein (a) was 22.2 ± 17.3 mg/dL (22.1 ± 15.9 mg/dL for males, and 22.1 ± 18.4 mg/dL for females). Patients with hypertension, coronary heart disease, cerebrovascular accident, microalbuminuria and proteinuria presented a statistically significant increased level of lipoprotein (a). Similarly, the patients with hyperlipoprotein (a) (≥ 30 mg/dL) presented significantly increased levels of urea and total cholesterol. In the multivariate regression model, the level of lipoprotein (a) is positively correlated with coronary heart disease and diabetic nephropathy (P < 0.01 and P < 0.005, respectively). Conclusions The elevation of plasma levels of lipoprotein (a) are associated with the development of coronary heart disease and diabe tic nephropathy. Therefore, we consider that the determination of lipoprotein (a) may be a prognostic marker of vascular complications in patients with type 2 diabetes mellitus.

Use of Expert Consensus to Improve Atherogenic Dyslipidemia Management

INTRODUCTION AND OBJECTIVES Although atherogenic dyslipidemia is a recognized cardiovascular risk factor, it is often underassessed and thus undertreated and poorly controlled in clinical practice. The objective of this study was to reach a multidisciplinary consensus for the establishment of a set of clinical recommendations on atherogenic dyslipidemia to optimize its prevention, early detection, diagnostic evaluation, therapeutic approach, and follow-up. METHODS After a review of the scientific evidence, a scientific committee formulated 87 recommendations related to atherogenic dyslipidemia, which were grouped into 5 subject areas: general concepts (10 items), impact and epidemiology (4 items), cardiovascular risk (32 items), detection and diagnosis (19 items), and treatment (22 items). A 2-round modified Delphi method was conducted to compare the opinions of a panel of 65 specialists in cardiology (23%), endocrinology (24.6%), family medicine (27.7%), and internal medicine (24.6%) on these issues. RESULTS After the first round, the panel reached consensus on 65 of the 87 items discussed, and agreed on 76 items by the end of the second round. Insufficient consensus was reached on 3 items related to the detection and diagnosis of atherogenic dyslipidemia and 3 items related to the therapeutic goals to be achieved in these patients. CONCLUSIONS The external assessment conducted by experts on atherogenic dyslipidemia showed a high level of professional agreement with the proposed clinical recommendations. These recommendations represent a useful tool for improving the clinical management of patients with atherogenic dyslipidemia. A detailed analysis of the current scientific evidence is required for those statements that eluded consensus.

Consensus on the Statin of Choice in Patients with Impaired Glucose Metabolism: Results of the DIANA Study

Introduction and ObjectivesDespite the recognized clinical benefit of statins on cardiovascular prevention, providing correct management of hypercholesterolaemia, possible adverse effects of their use cannot be disregarded. Previously published data shows that there is a risk of developing diabetes mellitus or experiencing changes in glucose metabolism in statin-treated patients. The possible determining factors are the drug characteristics (potency, dose), patient characteristics (kidney function, age, cardiovascular risk and polypharmacy because of multiple disorders) and the pre-diabetic state.MethodsIn order to ascertain the opinion of the experts (primary care physicians and other specialists with experience in the management of this type of patient) we conducted a Delphi study to evaluate the consensus rate on diverse aspects related to the diabetogenicity of different statins, and the factors that influence their choice.ResultsConsensus was highly significant concerning aspects such as the varying diabetogenicity profiles of different statins, as some of them do not significantly worsen glucose metabolism. There was an almost unanimous consensus that pitavastatin is the safest statin in this regard.ConclusionsFactors to consider in the choice of a statin regarding its diabetogenicity are the dose and patient-related factors: age, cardiovascular risk, diabetes risk and baseline metabolic parameters (which must be monitored during the treatment), as well as kidney function.

La diabetogenicidad de las estatinas: ¿son todas iguales? Estado de la cuestión

Statins are the cornerstone of cardiovascular prevention for general population, and in patients with type 2 diabetes mellitus (T2DM). However, statin therapy predisposes to type 2 diabetes, particularly in patients with predisposition to this condition. Some statins have been associated with increases in blood glucose in patients with or without DM2, and others have shown to have neutral effects, varying from one another their glucose or diabetogenic capacity. In many statin trials the incidence of DM2 has not been systematically evaluated and others the power to detect differences between statins is lacking. Evidence highest quality available comes from the meta-analysis of controlled clinical trials. The only controlled clinical trial to evaluate the incidence of new-onset T2DM is the J-PREDICT conducted with pitavastatin in patients with abnormal glucose tolerance. Preliminary results of this study show that pitavastatin is associated with a significant decrease in the incidence of de novo T2DM compared to only modification lifestyle. Therefore, pitavastatin may be an appropriate therapeutic alternative of choice to reduce vascular risk in patients with T2DM or at risk of presenting it.

Variabilidad del contenido de polifenoles de distintos tipos de vino y su potencial aplicación al conocimiento de sus efectos biológicos

Fundamento Los polifenoles del vino tienenpropiedades antioxidantes. Los distintos polifenolestienen acciones biologicas diferentessobre la aterogenesis y la carcinogenesis. Material y metodos Se estudia, medianteHPLC, la composicion de 5 polifenoles en16 vinos castellanos. Resultados La concentracion de polifenoleses muy variable para cada vino. La mayoriade los tintos estudiados tienen mayor cantidadde polifenoles que los blancos. Conclusiones La diversa composicion enpolifenoles de cada vino permite sospechardiferentes efectos biologicos para los distintosvinos.

Recommendations for the pharmacological treatment of hyperglycemia in type 2 diabetes

a En representacion del Grupo de Trabajo de Consensos y Guias Clinicas de la Sociedad Espanola de Diabetes, Espana b Sociedad Espanola de Arteriosclerosis (SEA), Espana c Sociedad Espanola de Cardiologia (SEC), Espana d Sociedad Espanola de Endocrinologia y Nutricion (SEEN), Espana e Sociedad Espanola de Farmacia Comunitaria (SEFAC), Espana f Sociedad Espanola de Medicina Familiar y Comunitaria (SEMFYC), Espana g Sociedad Espanola de Medicina Interna (SEMI), Espana h Sociedad Espanola de Medicos de Atencion Primaria (SEMERGEN), Espana i Sociedad Espanola de Medicos Generales y de Familia (SEMG), Espana j Sociedad Espanola de Nefrologia (SEN), Espana

[The REALIST (REsiduAl risk, LIpids and Standard Therapies) study: an analysis of residual risk attributable to lipid profile in acute coronary syndrome].

The R3i Foundation (Residual Risk Reduction Initiative), an independent, multinational and academic organization, is conducting the REALIST (Residual Risk, Lipids and Standard Therapies) study in 40 centers in different countries. This is a retrospective epidemiological study, designed to provide new data on the residual risk of major coronary events attributable to lipid abnormalities in patients receiving the current standard treatment. The initial results are expected in mid 2010, and the overall results at the end of 2010.