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Ischemic heart disease continues to cause high morbidity and mortality. Its prevalence is expected to increase due to population aging, and its prevention is a major goal of health policies. The risk of developing ischemic heart disease is related to a complex interplay between genetic, environmental, and lifestyle factors. In the last decade, considerable progress has been made in knowledge of the genetic architecture of this disease. This narrative review provides an overview of current knowledge of the genetics of ischemic heart disease and of its translation to clinical practice: identification of new therapeutic targets, assessment of the causal relationship between biomarkers and disease, improved risk prediction, and identification of responders and nonresponders to specific drugs (pharmacogenomics).

Background and aims The aim of this study was to perform a systematic review of the association between DNA methylation and coronary heart disease (CHD) or related atherosclerotic traits. Methods A systematic review was designed. The condition of interest was DNA methylation, and the outcome was CHD or other atherosclerosis-related traits. Three DNA methylation approaches were considered: global methylation, candidate-gene, and epigenome-wide association studies (EWAS). A functional analysis was undertaken using the Ingenuity Pathway Analysis software. Results In total, 51 articles were included in the analysis: 12 global methylation, 34 candidate-gene and 11 EWAS, with six studies using more than one approach. The results of the global methylation studies were inconsistent. The candidate-gene results were consistent for some genes, suggesting that hypermethylation in ESRα , ABCG1 and FOXP3 and hypomethylation in IL-6 were associated with CHD. The EWAS identified 84 genes showing differential methylation associated with CHD in more than one study. The probability of these findings was −5 . One third of these genes have been related to obesity in genome-wide association studies. The functional analysis identified several diseases and functions related to these set of genes: inflammatory, metabolic and cardiovascular disease. Conclusions Global DNA methylation seems to be not associated with CHD. The evidence from candidate-gene studies was limited. The EWAS identified a set of 84 genes highlighting the relevance of obesity, inflammation, lipid and carbohydrate metabolism in CHD. This set of genes could be prioritized in future studies assessing the role of DNA methylation in CHD.

Background: ST Segment Elevation Acute myocardial infarction (STEMI) preferred treatment is culprit artery reperfusion with primary percutaneous coronary intervention (PPCI). We ought to analyze the benefit of early reperfusion vs. optimal medical therapy in STEMI before and after the set-up of a regional STEMI network that prioritizes PPCI. Methods: Between January 2002 and December 2013, 1268 STEMI patients were consecutively admitted in a University Hospital. Patients were classified in two groups: pre-STEMI Network (January 2002-June 2009; n = 670) and post-STEMI network (July 2009-December 2013; n = 598). Vital status was available at 2-year follow-up. Results: The STEMI network increased reperfusion (89.2% vs 64.4%, p < 0.001) mainly using PCI (99.0% vs 43.9%, p < 0.001). In univariate analysis, in-hospital mortality was significantly lower in the post-STEMI network period (2.51% vs. 7.16%, p < 0.001). After multivariate adjustment, including age, sex, comorbidities, severity and reperfusion therapy, a trend to a lower in-hospital mortality was observed (post-Network OR: 0.50, 95% CI: 0.16-1.59, p = 0.24); this trend disappeared when optimal medical therapy was included in the model (post-Network OR: 1.14, 95% CI: 0.32-4.08, p = 0.840). No differences in 2-year mortality were observed (post-Network HR: 0.83; CI 95%: 0.55-1.25, p = 0.37). Conclusion: A STEMI network with PPCI 24/7 improved reperfusion therapy, resulting in an increase on PPCI. Despite in-hospital mortality decreased with a STEMI network, 2-year mortality remained similar in both periods, pre- and post-Network. Optimal medical therapy could be as important as reperfusion therapy in a STEMI reperfusion network.

Introduction: Clinical decision support systems (CDSS) are computer systems designed to assist clinicians with patient-related decision making, such as diagnosis and treatment. CDSS have shown to improve both patient outcomes and cost of care.Methods: A multi-center observational prospective study was conducted. Ten physicians agreed to participate. Seventy-seven patients with high or very high cardiovascular risk were included. After using CDSS for dyslipidemia (HTE-DLPR) for a 3 months period, participants were asked to evaluate their experience with HTE-DLPR using a quality of experience questionnaire (QoE) tool for mHealth applications.Results: Total score on the QoE was 3.89 out of 5. The highest scores were received for precision, ease of use and content quality. The lowest scores were given to security, appearance and performance. Physicians were in strong agreement with the 1st HTEDLPR recommendation in 86.1% and the system’s use was described as comfortablein 85% of cases. Users positively evaluated the development of a new version of HTEDLPR in the future receiving a total score of 4.25 out of 5.Conclusions: A CDSS for dyslipidemia (HTE-DLP) has been positively evaluated by physicians using QoE questionnaire.

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with stroke, cognitive impairment, and cardiovascular death. Some predisposing factors - as aging, diabetes, hypertension - induce and maintain electrophysiological and ultrastructural remodeling that usually includes fibrosis. Interatrial conduction disturbances play a crucial role in the initiation of atrial fibrosis and in its associated complications. The diagnosis of interatrial blocks (IABs) is easy to perform using the surface ECG. IAB is classified as partial when the P wave duration is ≥120ms, and advanced if the P wave also presents a biphasic pattern in II, III and aVF. IAB is very frequent in the elderly and, particularly in the case of the advanced type, is associated with AF, AF recurrences, stroke, and dementia. The anticoagulation in elderly patients at high risk of AF without documented arrhythmias is an open issue but recent data suggest that it might have a role, particularly in elderly patients with structural heart disease, high CHA2DS2VASc (Congestive heart failure/left ventricular dysfunction, Hypertension, Age≥75 [doubled], Diabetes, Stroke [doubled] - Vascular disease, Age 65-74, and Sex category [female]), and advanced IAB. In this debate, we discuss the association of surface ECG IAB, a marker of atrial fibrosis, with AF and stroke. We also present the rationale that justifies further studies regarding anticoagulation in some of these patients. Sin financiación 1.812 JCR (2017) Q3, 80/128 Cardiac and Cardiovascular Systems UEM

Malalties cardiovasculars; Nivell Educacional; Diabetis Enfermedades cardiovasculares; Nivel Educacional; Diabetes Cardiovascular Diseases; Educational Level; Diabetes Education and cardiovascular disease (CVD) are inversely associated but the mediating factors have not been totally elucidated. Our aim was to analyze the mediating role of modifiable risk factors. Cohort study using the REGICOR population cohorts. Participants without previous CVD were included (n = 9226). Marginal structural models were used to analyze the association between education and CVD incidence at 6 years of follow-up. Mediation by modifiable risk factors (diabetes, dyslipidemia, hypertension, smoking, body mass index, and physical activity) was assessed using the counterfactual framework. Participants with a university degree had a CVD incidence hazard ratio (HR) of 0.51 (95% confidence interval (CI) = 0.30, 0.85), compared to those with primary or lower education. Only hypertension, BMI, and diabetes mediated the association between education and CVD incidence, accounting for 26% of the association (13.9, 6.9, and 5.2%, respectively). Sensitivity analyses showed that hypertension was the strongest mediator (average causal mediation effect [95% CI] = increase of 2170 days free of CVD events [711, 4520]). The association between education and CVD incidence is partially mediated by hypertension, BMI, and diabetes. Interventions to decrease the prevalence of these risk factors could contribute to diminish the CVD inequalities associated with educational level.

Objective To develop and validate a short questionnaire to estimate physical activity (PA) practice and sedentary behavior for the adult population. Methods The short questionnaire was developed using data from a cross-sectional population-based survey (n = 6352) that included the Minnesota leisure-time PA questionnaire. Activities that explained a significant proportion of the variability of population PA practice were identified. Validation of the short questionnaire included a cross-sectional component to assess validity with respect to the data collected by accelerometers and a longitudinal component to assess reliability and sensitivity to detect changes (n = 114, aged 35 to 74 years). Results Six types of activities that accounted for 87% of population variability in PA estimated with the Minnesota questionnaire were selected. The short questionnaire estimates energy expenditure in total PA and by intensity (light, moderate, vigorous), and includes 2 questions about sedentary behavior and a question about occupational PA. The short questionnaire showed high reliability, with intraclass correlation coefficients ranging between 0.79 to 0.95. The Spearman correlation coefficients between estimated energy expenditure obtained with the questionnaire and the number of steps detected by the accelerometer were as follows: 0.36 for total PA, 0.40 for moderate intensity, and 0.26 for vigorous intensity. The questionnaire was sensitive to detect changes in moderate and vigorous PA (correlation coefficients ranging from 0.26 to 0.34). Conclusion The REGICOR short questionnaire is reliable, valid, and sensitive to detect changes in moderate and vigorous PA. This questionnaire could be used in daily clinical practice and epidemiological studies., This work was supported by the following sources: a. The Spanish Ministry of Economy through the Carlos III Health Institute [PI10/02319] (LM), www.isciii.es; b. The Spanish Ministry of Economy through the Carlos III Health Institute Red de Investigacion Cardiovascular [RD12/0042] (RE), www.isciii.es; c. The Spanish Ministry of Economy through the Carlos III Health Institute Red de Investigacion Cardiovascular [RD12/0042] (JM), www.isciii.es; and d. Agenda de Gestio Ajuts Universitaris de Recerca [2014 SGR 240] (JM), http://agaur.gencat.cat

Resumen Introduccion y objetivos Los objetivos del estudio son analizar en poblacion espanola la asociacion entre dos variantes geneticas (rs2200733 y rs7193343) y el riesgo de sufrir fibrilacion auricular y realizar una revision sistematica y un metanalisis de estas asociaciones. Metodos Estudio de casos y controles con 257 casos de fibrilacion auricular y 379 controles. Los casos eran donantes del Banco Nacional de ADN; los controles participaron en un estudio transversal de base poblacional. La genotipificacion se realizo mediante pruebas TaqMan. Se realizo una busqueda bibliografica sistematica, dos revisores independientes extrajeron la informacion necesaria. Se realizo un metanalisis, un analisis de heterogeneidad y de metarregresion para identificar las variables que explicaran la heterogeneidad entre estudios. Resultados En nuestra poblacion se observa una asociacion entre el rs2200733 y la presencia de fibrilacion auricular (odds ratio = 1,87; intervalo de confianza del 95%, 1,30-2,70), pero no con el rs7193343 (odds ratio = 1,18; intervalo de confianza del 95%, 0,80-1,73). En el metanalisis, se observo una asociacion de ambas variantes con la fibrilacion auricular: odds ratio = 1,71 (intervalo de confianza del 95%, 1,54-1,90) para el rs2200733 y odds ratio = 1,18 (intervalo de confianza del 95%, 1,11-1,25) para el rs7193343. En la asociacion entre el rs2200733 y la fibrilacion auricular se observo heterogeneidad entre estudios, parcialmente relacionada con el diseno del estudio, con mayor magnitud de asociacion en estudios de casos y controles (odds ratio = 1,83) que en cohortes (odds ratio = 1,41). Conclusiones Las variantes rs2200733 y rs7193343 se asocian con mayor riesgo de fibrilacion auricular. Los estudios de casos y controles tienden a sobrestimar la magnitud de la asociacion entre estas variantes geneticas y la fibrilacion auricular.

A B S T R A C T Introduction and objectives: The objectives of this study were to analyze the association between two genetic variants (rs2200733 and rs7193343) in a Spanish population and the risk of developing atrial fibrillation, and to carry out a systematic review and meta-analysis of these associations. Methods: We performed a case-control study involving 257 case patients with atrial fibrillation and 379 controls. The case patients were individuals who had donated samples to the Spanish National DNA Bank; the controls were participating in a population-based cross-sectional study. Genotyping was carried out using a TaqMan assay. We conducted a systematic literature search in which 2 independent reviewers extracted the necessary information. The study involved a meta-analysis, a heterogeneity analysis, and a meta-regression analysis to identify the variables that explain the heterogeneity across studies. Results: In our population, the presence of atrial fibrillation was found to be associated with rs2200733 (odds ratio = 1.87; 95% confidence interval, 1.30-2.70), but not with rs7193343 (odds ratio = 1.18; 95% confidence interval, 0.80-1.73). In the meta-analysis, we observed an association between atrial fibrillation and both variants: odds ratio = 1.71 (95% confidence interval, 1.54-1.90) for rs2200733 and odds ratio = 1.18 (95% confidence interval, 1.11-1.25) for rs7193343. We observed heterogeneity among the studies dealing with the association between rs2200733 and atrial fibrillation, partially related to the study design, and the strength of association was greater in case-control studies (odds ratio = 1.83) than in cohort studies (odds ratio = 1.41). Conclusions: Variants rs2200733 and rs7193343 are associated with a higher risk of atrial fibrillation. Case-control studies tend to overestimate the strength of association between these genetic variants and atrial fibrillation.

Resumen Introduccion y objetivos No se ha estudiado en comparacion con normopeso el perfil de los biomarcadores relacionados con obesidad, sindrome metabolico y diabetes mellitus. Se pretende caracterizar el perfil de biomarcadores en el continuo de riesgo metabolico definido por la transicion de normopeso a obesidad, sindrome metabolico y diabetes mellitus. Metodos Analisis transversal de datos agrupados procedentes de siete estudios poblacionales espanoles. Se determinaron 20 biomarcadores del metabolismo de los hidratos de carbono y los lipidos, inflamatorios, de coagulacion, oxidacion, hemodinamicos y de lesion miocardica. Se realizaron modelos de regresion multinomial ajustados para los fenotipos sano, obesidad, sindrome metabolico y diabetes mellitus. Resultados Se incluyo a 2.851 participantes, con media de edad de 57,4 ± 8,8 anos; 1.269 (44,5%) eran varones; 464 sujetos tenian obesidad; 443, sindrome metabolico; 473, diabetes mellitus, y 1.471, normopeso (sujetos sanos). Los biomarcadores que mostraron asociacion positiva significativa con al menos uno de los fenotipos clinicos de interes fueron la proteina C reactiva de alta sensibilidad, la apolipoproteina B100, la leptina y la insulina. La apolipoproteina A1 y la adiponectina mostraron asociacion negativa. Conclusiones El grupo de normopeso, y algo menos la obesidad, se diferencian del sindrome metabolico y la diabetes mellitus en su perfil metabolico, inflamatorio y lipidico, lo que indica la relevancia de estos mecanismos en el continuo del riesgo metabolico. Estas diferencias son menores entre el sindrome metabolico y la diabetes mellitus.

Introduction Blood pressure increases in cold periods, but its implications on prevalence of hypertension and on individual progression to hypertension remain unclear. Our aim was to develop a pre-screening test for identifying candidates to suffer hypertension only in cold months among non-hypertensive subjects. Methods We included 95,277 subjects registered on a primary care database from Girona (Catalonia, Spain), with ≥3 blood pressure measures recorded between 2003 and 2009 and distributed in both cold (October–March) and warm (April–September) periods. We defined four blood pressure patterns depending on the presence of hypertension through these periods. A Cox model determined the risk to develop vascular events associated with blood pressure patterns. A logistic regression distinguished those nonhypertensive individuals who are more prone to suffer cold-induced hypertension. Validity was assessed on the basis of calibration (using Brier score) and discrimination (using the area under the receiver operating characteristics). Results In cold months, the mean systolic blood pressure increased by 3.3±0.1 mmHg and prevalence of hypertension increased by 8.2%. Cold-induced hypertension patients were at higher vascular events risk (Hazard ratio=1.44 [95% Confidence interval 1.15–1.81]), than nonhypertensive individuals. We identified age, diabetes, body mass index and prehypertension as the major contributing factors to cold-induced hypertension onset. Discussion Hypertension follows a seasonal pattern in some individuals. We recommend screening for hypertension during the cold months, at least in those nonhypertensive individuals identified as cold-induced hypertensive by this assessment tool.

Objective To derive and validate a set of functions to predict coronary heart disease (CHD) and stroke, and validate the Framingham-REGICOR function. Method Pooled analysis of 11 population-based Spanish cohorts (1992–2005) with 50,408 eligible participants. Baseline smoking, diabetes, systolic blood pressure (SBP), lipid profile, and body mass index were recorded. A ten-year follow-up included re-examinations/telephone contact and cross-linkage with mortality registries. For each sex, two models were fitted for CHD, stroke, and both end-points combined: model A was adjusted for age, smoking, and body mass index and model B for age, smoking, diabetes, SBP, total and HDL cholesterol, and for hypertension treatment by SBP, and age by smoking and by SBP interactions. Results The 9.3-year median follow-up accumulated 2973 cardiovascular events. The C-statistic improved from model A to model B for CHD (0.66 to 0.71 for men; 0.70 to 0.74 for women) and the combined CHD-stroke end-points (0.68 to 0.71; 0.72 to 0.75, respectively), but not for stroke alone. Framingham-REGICOR had similar C-statistics but overestimated CHD risk. Conclusions The new functions accurately estimate 10-year stroke and CHD risk in the adult population of a typical southern European country. The Framingham-REGICOR function provided similar CHD prediction but overestimated risk.

Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.

Background The use of validated multivariate cardiovascular predictive models in a population setting is of interest for public health policy makers. We aimed to validate the estimations of the CASSANDRA model (coronary heart disease (CHD) incidence and CHD risk distribution), considering the population changes in age, sex and CHD risk factors prevalence in a 10-year period. Methods We compared the projected CHD incidence estimated with CASSANDRA with that observed in the Girona Heart Registry (REGICOR) for 1995–2004 and 2000–2009 in the population of Girona (Spain) aged 35–74 years. We used official age and sex distributions for this population. Baseline cardiovascular risk factors prevalence and the distribution of cardiovascular risk were obtained from three cross-sectional studies performed in 1995, 2000 and 2005. To validate the future distribution of cardiovascular risk, we tested the yearly CHD risk variance over the study period. Results No significant differences between the estimated and observed annual CHD incidence per 100 000 men were found in 1995–2004 (CASSANDRA=457.8 and REGICOR=420.3, incidence rate ratio (IRR) (95% CI)=0.92 (0.89 to 0.96)) and in 2000–2009 (441.4 and 409.6, respectively, IRR=0.93 (0.90 to 0.96)). However, overpredictions of 18% and 22%, respectively, were observed in women (198.8 and 160.4, IRR=0.82 (0.77 to 0.86), and 197.1 and 152.8, IRR=0.78 (0.74 to 0.83), respectively). No significant differences were found in the CHD risk variance in the three different cross-sectional studies. Conclusions The CASSANDRA model produces valid estimates, particularly in men, of the future burden of disease and in the distribution of cardiovascular risk in individuals aged 35–74 years.

Aims Diagnosis of Type-2 Brugada pattern remains challenging and it could be confused with other electrocardiogram (ECG) patterns presenting an r ′-wave in leads V1–V2 like in healthy athletes. This could impact their ability to perform competitive sports. The aim of the study was to evaluate, as a proof of concept, the new ECG criteria to differentiate the Type-2 Brugada pattern from the ECG pattern of healthy athletes depicting an r ′-wave in leads V1–V2. Methods and results Surface ECGs from 50 patients with Brugada syndrome and type-2 Brugada pattern and 58 healthy athletes with an r ′-wave in leads V1–V2 were analysed. Different criteria based on the characteristics of the triangle formed by the ascendant and descendant arms of the r ′-wave in leads V1–V2 were compared. The duration of the base of the triangle at 0.5 mV (5 mm) from high take-off ≥160 ms (4 mm) has a specificity (SP) of 95.6%, sensitivity (SE) 85%, positive predictive value (PPV) 94.4%, and negative predictive value (NPV) 87.9%. The duration of the base of the triangle at the isoelectric line ≥60 ms (1.5 mm) in leads V1–V2 has an SP of 78%, SE 94.8%, PPV 79.3%, and NPV 93.5%. The ratio of the base at isoelectric line/height from the baseline to peak of r ′-wave in leads V1–V2 has an SP of 92.1%, SE 82%, PPV 90.1%, and NPV 83.3%. Conclusions The three new ECG criteria were accurate to distinguish the Type-2 Brugada pattern from the ECG pattern with an r ′-wave in healthy athletes. The duration of the base of the triangle at 0.5 mV from the high take-off is the easiest to measure and may be used in clinical practice.

Coronary artery disease (CAD) is the leading cause of death and disability worldwide, and its prevalence is expected to increase in the coming years. CAD events are caused by the interplay of genetic and environmental factors, the effects of which are mainly mediated through cardiovascular risk factors. The techniques used to study the genetic basis of these diseases have evolved from linkage studies to candidate gene studies and genome-wide association studies. Linkage studies have been able to identify genetic variants associated with monogenic diseases, whereas genome-wide association studies have been more successful in determining genetic variants associated with complex diseases. Currently, genome-wide association studies have identified approximately 40 loci that explain 6% of the heritability of CAD. The application of this knowledge to clinical practice is challenging, but can be achieved using various strategies, such as genetic variants to identify new therapeutic targets, personal genetic information to improve disease risk prediction, and pharmacogenomics. The main aim of this narrative review is to provide a general overview of our current understanding of the genetics of coronary artery disease and its potential clinical utility.

Resumen Introduccion y objetivos Analizar las diferencias en funcion del sexo en las caracteristicas clinicas, tratamiento y mortalidad a los 28 dias y a los 7 anos de un primer infarto de miocardio. Metodos Entre 2001 y 2003, 2.042 pacientes con un primer infarto de miocardio ingresaron consecutivamente en seis hospitales espanoles. Se recogen prospectivamente las caracteristicas clinicas, el tratamiento y la mortalidad a los 28 dias. Se dispone del estado vital a los 7 anos mediante consulta del Indice Nacional de Defunciones. Resultados Se incluyo a 449 mujeres y 1.593 varones con un primer infarto de miocardio. En comparacion con los varones, las mujeres eran mayores y tenian mayor prevalencia de hipertension y diabetes mellitus; tambien recibieron mas tratamiento con inhibidores de la enzima de conversion de la angiotensina, pero menos bloqueadores beta y trombolisis. No hubo diferencias en el uso de procedimientos invasivos. Las mujeres tuvieron mas infartos de miocardio sin elevacion del segmento ST o no clasificables (el 37,9 frente al 31,3% y el 9,8 frente al 6,1% respectivamente; p Conclusiones Hay diferencias clinicas y demograficas entre varones y mujeres que ingresan por un primer infarto de miocardio. El pronostico a corto plazo es similar en ambos sexos. La mortalidad a 7 anos de un primer infarto de miocardio es peor en varones que en mujeres. Estos resultados se observan en infartos agudos de miocardio con y sin elevacion del segmento ST.

Objectives To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population. Methods Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants. End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intima-media thickness (IMT) in the highest quintile and ankle-brachial index Results Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR = 1.70; 95% Confidence Interval: 1.02–2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI = 14.67% [4.90; 24.45], P = 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles). Conclusions OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions.

Cardiovascular diseases prevention strategies require refinement because their incidence decreases very slowly. Risk functions were developed by including classical cardiovascular risk factors (age, sex, smoking, diabetes, blood pressure, and basic lipid profile) in cohorts followed more than 10 years. They are reasonably precise for population screening of, principally, coronary artery disease risk, required in all cardiovascular primary prevention clinical guidelines. Coronary artery disease risk functions classify patients in risk strata to concentrate the maximum therapeutic and life style effort in the highest risk groups, in which the number needed to treat and cost-effectiveness are optimal. By communicating the relative risk and vascular age to patients, increased motivation to comply with the proposed drug and life-style modifications can be achieved. Approximately 20% of the population 35 to 74 years old has an intermediate risk that requires reclassification into high or low risk because they concentrate 35% of population coronary artery disease events. Several biomarkers (biochemical, genetic or imaging) are being tested to improve coronary artery disease risk functions precision. Computerized systems of health facilities should incorporate, automated risk calculation in order to support the preventive task of health care providers.Las estrategias de prevención de las enfermedades cardiovasculares necesitan refinamiento porque su incidencia se reduce muy lentamente. Las funciones de riesgo incorporaron los factores de riesgo clásicos (edad, sexo, consumo de tabaco, diabetes, presión arterial, y perfil lipídico básico) en cohortes seguidas generalmente más de 10 años. Son razonablemente precisas para el cribado poblacional del riesgo de enfermedad coronaria exigido en las guías de práctica clínica. Clasifican a los pacientes en niveles de riesgo para concentrar un mayor esfuerzo terapéutico y preventivo en los de mayor riesgo, y en los que el número necesario a tratar y el coste-efectividad son óptimos. Proporcionar el riesgo relativo y de la edad vascular al paciente, le motiva a cumplir seguir tratamientos y estilos de vida. Alrededor del 20% de la población de 35 a 74 años tiene riesgo intermedio y requiere reclasificación a alto o bajo riesgo porque concentra 35% de eventos poblacionales de enfermedad coronaria. Se ensayan nuevos biomarcadores (bioquímicos, genéticos o de imagen) para mejorar la precisión de las predicciones. Si los equipos informáticos de los sistemas de salud incorporaran el cálculo automatizado del riesgo se facilitaría la tarea preventiva del personal asistencial.

There is limited prospective evidence at population scale of the impacts of lifestyle and surrogate measures of general and abdominal adiposity on the transition of a metabolically healthy (absence of a metabolic disorder) overweight/obese (MHOO) phenotype to a metabolically abnormal overweight/obese (MAOO) phenotype. Therefore, we determined the relationship between 10-year body mass index (BMI), waist circumferences (WC), waist to height ratio (WHtR), and lifestyle changes and the transition of the MHOO phenotype.We conducted a prospective population-based study of 3,052 male and female Spaniards aged 25-74 years who were followed from 2000 through 2009. Diet and leisure-time physical activity were recorded on validated questionnaires. Weight, height, WC, blood lipids, glycemia, and blood pressure were measured. All variables were obtained at baseline (BL) and follow-up (FL). Participants with a BMI ≥ 25 kg/m(2) and free from hypercholesterolemia, hypertriglyceridemia, diabetes, hypertension, and low HDL and high LDL cholesterol levels were characterized as the MHOO phenotype. A composite healthy lifestyle index (HLI) was constructed by including temporary changes in 3 lifestyle variables (diet, leisure-time physical activity, and smoking).Initially, 20.8% of subjects had the MHOO phenotype; 49.2% of these shifted to MAOO phenotype. In multivariate analysis, changes in BMI, WC, WHtR were positively associated (p = 0.004, p = 0.018, and p = 0.016, respectively) with this transition. One unit increase in the HLI was associated with a 33% lower risk (p = 0.025) to the MAOO phenotype transition after adjusting for age, sex, educational level, and baseline energy intake, BMI, WC, and WHtR.The presence of metabolic disorders in the MHOO phenotype is predicted by an increase in anthropometric surrogate measures of general and abdominal adiposity. In contrast, a healthy lifestyle protects against a transition to the MAOO phenotype.

In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.

A B S T R A C T Acute coronary syndromes are a leading cause of mortality, morbidity, and health care cost in Spain. The aims of this report are to estimate the number of acute coronary syndromes cases in the Spanish population in 2013 and 2021, and the trend from 2005 to 2049. We estimated the number of acute coronary syndromes cases by sex and Spanish autonomous community using data from the most updated population and hospital registries. We present the estimated number of cases with an exact 95% confidence interval, assuming that the number of cases followed a Poisson distribution. There will be 115 752 acute coronary syndromes cases in Spain in 2013 (95% confidence interval, 114 822-116 687). Within 28 days, 39 086 of these patients will die and 85 326 will be hospitalized. Non-ST segment elevation acute coronary syndromes (56%) and acute myocardial infarction (81%) will be the most common admission and discharge diagnoses, respectively. We estimate approximately 109 772 acute coronary syndromes cases in 2021 (95% confidence interval, 108 868-110 635). The trend of acute coronary syndromes cases from 2005 to 2049 will stabilize in the population aged 25 to 74 years, but increase in those older than 74 years. Due to population aging, the number of acute coronary syndrome cases will increase overall until 2049, it may stabilize in the population aged

A B S T R A C T Acute coronary syndromes are a leading cause of mortality, morbidity, and health care cost in Spain. The aims of this report are to estimate the number of acute coronary syndromes cases in the Spanish population in 2013 and 2021, and the trend from 2005 to 2049. We estimated the number of acute coronary syndromes cases by sex and Spanish autonomous community using data from the most updated population and hospital registries. We present the estimated number of cases with an exact 95% confidence interval, assuming that the number of cases followed a Poisson distribution. There will be 115 752 acute coronary syndromes cases in Spain in 2013 (95% confidence interval, 114 822-116 687). Within 28 days, 39 086 of these patients will die and 85 326 will be hospitalized. Non-ST segment elevation acute coronary syndromes (56%) and acute myocardial infarction (81%) will be the most common admission and discharge diagnoses, respectively. We estimate approximately 109 772 acute coronary syndromes cases in 2021 (95% confidence interval, 108 868-110 635). The trend of acute coronary syndromes cases from 2005 to 2049 will stabilize in the population aged 25 to 74 years, but increase in those older than 74 years. Due to population aging, the number of acute coronary syndrome cases will increase overall until 2049, it may stabilize in the population aged

The estimation of the cardiovascular risk is important for guiding individual preventive strategies. Various functions are available and have been shown to provide an accurate estimation of risk. However, while the majority of individuals in the general population fall within categories of low and moderate risk, a high proportion of cardiovascular events also occur in individuals within these categories. Therefore, renewed efforts have been made recently to improve the predictive capacity of classical risk functions through the inclusion of new risk biomarkers, including genetic variants associated with coronary or cardiovascular diseases. In this narrative review, we will focus on the utility and limitations of cardiovascular risk functions, assessment of the predictive capacity of new biomarkers, current knowledge of genetic variants associated with clinical cardiovascular phenotypes, and their potential predictive value. We will also identify some priorities for future research in this area.

Las diferencias en mortalidad por cardiopatia isquemica entre paises europeos se describieron inicialmente durante el siglo pasado y, aunque menos espectaculares de lo que al principio se describio, actualmente las diferencias siguen siendo sustanciales. Se han propuesto tres hipotesis principales para explicar la paradoja del Mediterraneo: a) una subestimacion de la mortalidad por cardiopatia isquemica debida a deficiencias metodologicas; b) la hipotesis del tiempo insuficiente de latencia/induccion de la enfermedad, y c) el efecto protector de la dieta y el estilo de vida en los paises Mediterraneos. En este trabajo se presenta y se desarrolla una posible explicacion complementaria de la paradoja del Mediterraneo relacionada con las mayores prevalencia e incidencia de placas ateromatosas estables en esta zona.

Differences between European countries in coronary heart disease mortality were initially described in the 20th century, and albeit less dramatic than first reported, these differences remain substantial. Three main hypotheses have been proposed to explain the so-called “Mediterranean paradox”: a) underestimation of coronary heart disease mortality due to methodological flaws; b) the “lag time” hypothesis, and c) the traditional Mediterranean diet and lifestyle. In this manuscript we present and discuss another possible explanation for the Mediterranean paradox related to the higher prevalence and incidence of stable atheromatous plaques in this area.

Introducción y objetivos El grosor íntima-media carotídeo medido por ultrasonografía es un predictor de acontecimientos cardiovasculares barato y no invasivo. Se analizaron los valores de referencia del grosor íntima-media carotídeo en población española de 35-84 años y su asociación con los factores de riesgo cardiovascular (edad, tabaquismo, diabetes mellitus, presión de pulso, perfil lipídico e índice de masa corporal). Métodos Estudio transversal de base poblacional llevado a cabo en Girona (España). Se describieron los grosores íntima-media medio y máximo de la arteria carótida y sus tres segmentos (carótida común, interna y bulbo carotídeo). Se recogió información sobre factores de riesgo cardiovascular y se analizó su asociación con el grosor íntima-media carotídeo mediante modelos de regresión lineal. Resultados Se incluyó a 3.161 sujetos (el 54% mujeres), con una media de edad de 58 años. La media del grosor íntima-media carotídeo común fue mayor en los varones que en las mujeres (0,71 frente a 0,67 mm). Los principales predictores de esta medida fueron la edad (coeficiente para incremento de 10 años, 0,65 y 0,58 en varones y mujeres respectivamente), el tabaquismo en los varones (coeficiente, 0,26), el colesterol unido a lipoproteínas de alta densidad en las mujeres (coeficiente para incremento de 10 mg/dl, incremento de –0,08) y la presión de pulso en ambos sexos (coeficientes para incremento de 10 mmHg, 0,23 los varones y 0,08 las mujeres). Los resultados fueron similares en las medias de grosor íntima-media carotídeo de los tres segmentos. Conclusiones Este estudio de base poblacional muestra la amplitud de valores de referencia para el grosor íntima-media carotídeo en población española. Sus principales determinantes son la edad y la presión de pulso en ambos sexos. Abstract Introduction and objectives Carotid intima-media thickness as measured with ultrasonography is an inexpensive and noninvasive predictor of cardiovascular events. The objectives of this study were to determine the population reference ranges of carotid intima-media thickness for individuals aged 35-84 years in Spain and to analyze the association of carotid intima-media thickness with cardiovascular risk factors (age, smoking, diabetes, pulse pressure, lipid profile, and body mass index). Methods Population-based cross-sectional study conducted in Gerona (Spain). We described the mean and maximal values of carotid intima-media thickness of the carotid artery and of its 3 segments (common carotid, carotid bulb and internal carotid). We assessed cardiovascular risk factors and analyzed their association with carotid intima-media thickness using adjusted linear regression models.

A B S T R A C T Introduction and objectives: Carotid intima-media thickness as measured with ultrasonography is an inexpensive and noninvasive predictor of cardiovascular events. The objectives of this study were to determine the population reference ranges of carotid intima-media thickness for individuals aged 35-84 years in Spain and to analyze the association of carotid intima-media thickness with cardiovascular risk factors (age, smoking, diabetes, pulse pressure, lipid profile, and body mass index). Methods: Population-based cross-sectional study conducted in Gerona (Spain). We described the mean and maximal values of carotid intima-media thickness of the carotid artery and of its 3 segments (common carotid, carotid bulb and internal carotid). We assessed cardiovascular risk factors and analyzed their association with carotid intima-media thickness using adjusted linear regression models. Results: A total of 3161 individuals (54% women) were included, with mean age 58 years. Men showed significantly higher mean common carotid intima-media thickness than did women (0.71 vs 0.67 mm). The strongest predictors of this measure were age (coefficients for 10-year increase: 0.65 and 0.58 for women and men, respectively), smoking in men (coefficient: 0.26), high-density lipoprotein cholesterol in women (coefficient for 10 mg/dL, increase: 0.08) and pulse pressure in both sexes (coefficients for 10 mmHg increase: 0.08 and 0.23 for women and men, respectively). The results were similar for the mean carotid intima-media thickness of all the segments. Conclusions: This population-based study presents the reference ranges for carotid intima-media thickness in the Spanish population. The main determinants of carotid intima-media thickness were age and pulse pressure in both sexes.

The VI European Guidelines for Cardiovascular Prevention recommend combining population and high-risk strategies with lifestyle changes as a cornerstone of prevention, and propose the SCORE function to quantify cardiovascular risk. The guidelines highlight disease specific interventions, and conditions as women, young people and ethnic minorities. Screening for subclinical atherosclerosis with noninvasive imaging techniques is not recommended. The guidelines distinguish four risk levels (very high, high, moderate and low) with therapeutic objectives for lipid control according to risk. Diabetes mellitus confers a high risk, except for subjects with type 2 diabetes with less than 10 years of evolution, without other risk factors or complications, or type 1 diabetes of short evolution without complications. The decision to start pharmacological treatment of arterial hypertension will depend on the blood pressure level and the cardiovascular risk, taking into account the lesion of target organs. The guidelines don't recommend antiplatelet drugs in primary prevention because of the increased bleeding risk. The low adherence to the medication requires simplified therapeutic regimes and to identify and combat its causes. The guidelines highlight the responsibility of health professionals to take an active role in advocating evidence-based interventions at the population level, and propose effective interventions, at individual and population level, to promote a healthy diet, the practice of physical activity, the cessation of smoking and the protection against alcohol abuse.

SummaryLarge-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). The resulting catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We show that this catalogue can be used to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; we identify 3,230 genes with near-complete depletion of truncating variants, 72% of which have no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human “knockout” variants in protein-coding genes.

The prevalence of interatrial block (IAB) is high in the elderly, particularly in those with heart disease. Despite this high prevalence—and the association of IAB with the risk of atrial fibrillation (AF), stroke, and cognitive decline—little information exists about the prognosis of older patients with IAB. P-wave duration and morphology are associated with risk of developing AF, stroke, and cognitive decline in elderly patients with structural heart disease. The aim of the Interatrial Block and Yearly Events (BAYES) registry is to assess the impact of IAB on the risk of AF and stroke during 3 years of follow-up. A series of 654 ambulatory patients age ≥70 years with heart disease from 35 centers will be included in 3 similar-size groups of patients. Group A: normal P-wave duration (5 minutes and documented in any form of electrocardiographic recording; and (2) stroke. Results from this study might significantly improve the knowledge of IAB and its impact on the outcome of elderly patients with heart disease and could open the door to the use of anticoagulation therapy in some elderly patients with IAB. Sin financiación 2.733 JCR (2017) Q2, 57/128 Cardiac and Cardiovascular Systems UEM

Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (e.g. CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay between different classes of epigenetic processes in the lipid-related genomic regions. While epigenetic findings hold the potential to explain the interindividual variability in lipid profiles as well as the underlying mechanisms, they have yet to be translated into effective therapies for dyslipidemia.

Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia. P-wave duration and interatrial blocks (IAB) have been reported to be associated with AF. Our aim was to determine the individual and combined association of P-wave duration and advanced IAB morphology with AF.We designed an age-, sex-, and survey-matched case-control study nested in a population-based cohort (REGICOR: REgistre GIroní del COR). Two different surveys recruited a total of 9380 participants from 1999 to 2005; all participants were invited to a second examination between 2009 and 2013. For the present study, we selected participants aged 25 to 79 years with follow-up through the end of the study. All electrocardiograms were analyzed by 2 observers to determine P-wave duration and morphology (normal, partial, or advanced IAB).The median follow-up was 7.12 years. Eighty participants presented with AF, had a legible baseline electrocardiogram, and were included in the study, along with 160 controls. P-wave duration and the presence of partial or advanced IAB were associated with AF. When P-wave duration and morphology were considered together, only P-wave duration (≥ 110 milliseconds) showed an independent and strong association with AF. The odds ratio for AF of P-wave duration between 110-119, 120-129 and ≥ 130 milliseconds vs110 milliseconds were 5.33; 95%CI, 1.74-16.33, 5.08; 95%CI, 1.73-14.90 and 5.44; 95%CI, 1.95-15.15, respectively.A P-wave longer than 110 milliseconds increases the risk of AF. Advanced IAB morphology did not seem to provide an additional AF risk beyond that of P-wave duration.

Introduction and objectives To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population. Methods Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively. Results Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P < .001 in both sexes and with all functions). The area under the ROC curve with the original SCORE was 0.68 in men and 0.69 in women. Conclusions All versions of the SCORE functions available in Spain significantly overestimate the cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate.

Background Diagnosis of unrecognized myocardial infarction (UMI) remains an open question in epidemiological and clinical studies, inhibiting effective secondary prevention of myocardial infarction. We aimed to determine the prevalence and incidence of Q-wave UMI in asymptomatic individuals aged 35 to 74years, and to ascertain the positive predictive value (PPV) of asymptomatic Q-wave to diagnose UMI. Methods Two population-based cross-sectional studies were conducted, in 2000 (with 10-year follow-up) and in 2005. A baseline electrocardiogram was obtained for each participant. Imaging techniques (echocardiography, cardiac magnetic resonance imaging, and myocardial perfusion single-photon emission computerized tomography) were used to confirm UMI in patients with asymptomatic Q-wave. Results The prevalence of confirmed Q-wave UMI in the 5580 participants was 0.18% (95% confidence interval [CI]: 0.10–0.33) and the incidence rate was 27.1 Q-wave UMI per 100,000person-years. The proportion of confirmed Q-wave UMI with respect to all prevalent MI was 8.1% (95% CI: 4.4–14.2). The PPV of asymptomatic Q-wave to diagnose Q-wave UMI was 29.2% (95% CI: 18.2–43.2%) overall, but much higher (75%, 95% CI: 40.9–92.9%) in participants with 10-year CHD risk ≥10%, compared to lower-risk participants. Conclusion Opportunistic identification of asymptomatic Q-waves by routine electrocardiogram overestimates actual Q-wave UMI, which represents 8% to 13% of all myocardial infarction in the population aged 35 to 74years. This overestimation is particularly high in the population at low cardiovascular risk. In epidemiological studies and in clinical practice, diagnosis of a pathologic Q-wave in asymptomatic patients requires detailed analysis of imaging tests to confirm or rule out myocardial necrosis.

Background: The biological functions of high-density lipoproteins (HDLs) contribute to explaining the cardioprotective role of the lipoprotein beyond quantitative HDL cholesterol levels. A few small-scale interventions with a single antioxidant have improved some HDL functions. However, to date, no long-term, large-scale, randomized controlled trial has been conducted to assess the effects of an antioxidant-rich dietary pattern (such as a traditional Mediterranean diet [TMD]) on HDL function in humans. Methods: This study was performed in a random subsample of volunteers from the PREDIMED Study (Prevención con Dieta Mediterránea; n=296) after a 1-year intervention. We compared the effects of 2 TMDs, one enriched with virgin olive oil (TMD-VOO; n=100) and the other enriched with nuts (TMD-Nuts; n=100), with respect to a low-fat control diet (n=96). We assessed the effects of both TMDs on the role of HDL particles on reverse cholesterol transport (cholesterol efflux capacity, HDL ability to esterify cholesterol, and cholesteryl ester transfer protein activity), HDL antioxidant properties (paraoxonase-1 arylesterase activity and total HDL antioxidant capacity on low-density lipoproteins), and HDL vasodilatory capacity (HDL ability to induce the release of nitric oxide in endothelial cells). We also studied the effects of a TMD on several HDL quality-related characteristics (HDL particle oxidation, resistance against oxidative modification, main lipid and protein composition, and size distribution). Results: Both TMDs increased cholesterol efflux capacity relative to baseline ( P =0.018 and P =0.013 for TMD-VOO and TMD-Nuts, respectively). The TMD-VOO intervention decreased cholesteryl ester transfer protein activity (relative to baseline, P =0.028) and increased HDL ability to esterify cholesterol, paraoxonase-1 arylesterase activity, and HDL vasodilatory capacity (relative to control, P =0.039, P =0.012, and P =0.026, respectively). Adherence to a TMD induced these beneficial changes by improving HDL oxidative status and composition. The 3 diets increased the percentage of large HDL particles (relative to baseline, P Conclusions: The TMD, especially when enriched with virgin olive oil, improved HDL atheroprotective functions in humans. Clinical Trial Registration: URL: http://www.controlled-trials.com . Unique identifier: ISRCTN35739639.

Background— We evaluated whether including multilocus genetic risk scores (GRSs) into the Framingham Risk Equation improves the predictive capacity, discrimination, and reclassification of asymptomatic individuals with respect to coronary heart disease (CHD) risk. Methods and Results— We performed a cohort study among 51 954 European-ancestry members of a Northern California integrated healthcare system (67% female; mean age 59) free of CHD at baseline (2007–2008). Four GRSs were constructed using between 8 and 51 previously identified genetic variants. After a mean (±SD) follow-up of 5.9 (±1.5) years, 1864 incident CHD events were documented. All GRSs were linearly associated with CHD in a model adjusted by individual risk factors: hazard ratio (95% confidence interval) per SD unit: 1.21 (1.15–1.26) for GRS_8, 1.20 (1.15–1.26) for GRS_12, 1.23 (1.17–1.28) for GRS_36, and 1.23 (1.17–1.28) for GRS_51. Inclusion of the GRSs improved the C statistic (ΔC statistic =0.008 for GRS_8 and GRS_36; 0.007 for GRS_12; and 0.009 for GRS_51; all P Conclusions— Our results demonstrate significant and clinically relevant incremental discriminative/predictive capability of 4 multilocus GRSs for incident CHD among subjects of European ancestry.

Higher monetary diet cost is associated with healthier food choices and better weight management. How changes in diet cost affect changes in diet quality and weight remains unknown. The aim of this study was to assess the impact of changes in individual monetary diet cost on changes in diet quality, measured by the modified Mediterranean diet score recommendations (MDS-rec) and by energy density (ED), as well as changes in weight and BMI. We conducted a prospective, population-based study of 2181 male and female Spaniards aged between 25 and 74 years, who were followed up to the 2009-2010 academic year. We measured weight and height and recorded dietary data using a validated FFQ. Average food cost was calculated from official Spanish government data. We fitted multivariate linear and logistic regression models. The average daily diet cost increased from 3·68(SD0.0·89)€/8·36 MJ to 4·97(SD1·16)€/8·36 MJ during the study period. This increase was significantly associated with improvement in diet quality (Δ ED and Δ MDS-rec; P

Objectives To determine whether the risk of cardiovascular mortality associated with cardiorenal syndrome subtype 1 (CRS1) in patients who were hospitalized for acute coronary syndrome (ACS) was greater than the expected risk based on the sum of its components, to estimate the predictive value of CRS1, and to determine whether the severity of CRS1 worsens the prognosis. Methods Follow-up study of 1912 incident cases of ACS for 1 year after discharge. Cox regression models were estimated with time to event (in-hospital death, and readmission or death during the first year after discharge) as the dependent variable. Results The incidence of CRS1 was 9.2/1000 person-days of hospitalization (95% CI = 8.1-10.5), but these patients accounted for 56.6% (95% CI = 47.4-65.) of all mortality. The positive predictive value of CRS1 was 29.6% (95% CI = 23.9-36.0) for in-hospital death, and 51.4% (95% CI = 44.8-58.0) for readmission or death after discharge. The risk of in-hospital death from CRS1 (RR = 18.3; 95% CI = 6.3-53.2) was greater than the sum of risks associated with either acute heart failure (RR = 7.6; 95% CI = 1.8-31.8) or acute kidney injury (RR = 2.8; 95% CI = 0.9-8.8). The risk of events associated with CRS1 also increased with syndrome severity, reaching a RR of 10.6 (95% CI = 6.2-18.1) for in-hospital death at the highest severity level. Conclusions The effect of CRS1 on in-hospital mortality is greater than the sum of the effects associated with each of its components, and it increases with the severity of the syndrome. CRS1 accounted for more than half of all mortality, and its positive predictive value approached 30% in-hospital and 50% after discharge.

Based on the 2 main frameworks for evaluating scientific evidence (SEC and GRADE) European cardiovascular prevention guidelines recommend interventions across all life stages using a combination of population-based and high-risk strategies with diet as the cornerstone of prevention. The evaluation of cardiovascular risk (CVR) incorporates HDL levels and psychosocial factors, a very high risk category, and the concept of age-risk. They also recommend cognitive-behavioural methods (e.g., motivational interviewing, psychological interventions) led by health professionals and with the participation of the patient's family, to counterbalance psychosocial stress and reduce CVR through the institution of positive habits such as a healthy diet, physical activity, smoking cessation, and adherence to treatment. Additionally, public health interventions—such as smoking ban in public areas or the elimination of trans fatty acids from the food chain—are also essential. Other innovations include abandoning antiplatelet therapy in primary prevention and the recommendation of maintaining blood pressure within the 130-139/80-85 mmHg range in diabetic patients and individuals with high CVR. Finally, due to the significant impact on patient progress and medical costs, special emphasis is given to the low therapeutic adherence levels observed. In sum, improving cardiovascular prevention requires a true partnership among the political class, public administrations, scientific and professional associations, health foundations, consumer associations, patients and their families. Such partnership would promote population-based and individual strategies by taking advantage of the broad spectrum of scientific evidence available, from clinical trials to observational studies and mathematical models to evaluate population-based interventions, including cost-effectiveness analyses. Resumen: Las guías europeas de prevención cardiovascular contemplan 2 sistemas de evaluación de la evidencia (SEC y GRADE) y recomiendan combinar las estrategias poblacional y de alto riesgo, interviniendo en todas las etapas de la vida, con la dieta como piedra angular de la prevención. La valoración del riesgo cardiovascular (RCV) incorpora los niveles de HDL y los factores psicosociales, una categoría de muy alto riesgo y el concepto edad-riesgo. Se recomienda el uso de métodos cognitivo-conductuales (entrevista motivadora, intervenciones psicológicas), aplicados por profesionales sanitarios, con la participación de familiares de los pacientes, para contrarrestar el estrés psicosocial y reducir el RCV mediante dietas saludables, entrenamiento físico, abandono del tabaco y cumplimiento terapéutico. También se requieren medidas de salud pública, como la prohibición de fumar en lugares públicos o eliminar los ácidos grasos trans de la cadena alimentaria. Otras novedades consisten en desestimar el tratamiento antiagregante en prevención primaria y la recomendación de mantener la presión arterial dentro del rango 130-139/80-85 mmHg en pacientes diabéticos o con RCV alto. Se destaca el bajo cumplimiento terapéutico observado, porque influye en el pronóstico de los pacientes y en los costes sanitarios. Para mejorar la prevención cardiovascular se precisa una verdadera alianza entre políticos, administraciones, asociaciones científicas y profesionales de la salud, fundaciones de salud, asociaciones de consumidores, pacientes y sus familias, que impulse la estrategia tanto poblacional como individual mediante el uso de toda la evidencia científica disponible, desde ensayos clínicos hasta estudios observacionales y modelos matemáticos para evaluar intervenciones a nivel poblacional, incluyendo análisis de coste-efectividad. Keywords: Cardiovascular prevention, Cardiovascular risk, Cardiovascular diseases, Clinical practice guidelines, Palabras clave: Prevención cardiovascular, Riesgo cardiovascular, Enfermedades cardiovasculares, Guías de práctica clínica

BACKGROUND: Evidence is lacking about the effectiveness of risk reduction interventions in patients with asymptomatic peripheral arterial disease. OBJECTIVES: This study aimed to assess whether statin therapy was associated with a reduction in major adverse cardiovascular events (MACE) and mortality in this population. METHODS: Data were obtained from 2006 through 2013 from the Catalan primary care system's clinical records database (SIDIAP). Patients age 35 to 85 years with an ankle-brachial index ≤0.95 and without clinically recognized cardiovascular disease (CVD) were included. Participants were categorized as statins nonusers or new-users (first prescription or represcribed after at least 6 months) and matched 1:1 by inclusion date and propensity score for statin treatment. Conditional Cox proportional hazards modeling was used to compare the groups for the incidence of MACE (myocardial infarction, cardiac revascularization, and ischemic stroke) and all-cause mortality. RESULTS: The matched-pair cohort included 5,480 patients (mean age 67 years; 44% women) treated/nontreated with statins. The 10-year coronary heart disease risk was low (median: 6.9%). Median follow-up was 3.6 years. Incidence of MACE was 19.7 and 24.7 events per 1,000 person-years in statin new-users and nonusers, respectively. Total mortality rates also differed: 24.8 versus 30.3 per 1,000 person-years, respectively. Hazards ratios were 0.80 for MACE and 0.81 for overall mortality. The 1-year number needed to treat was 200 for MACE and 239 for all-cause mortality. CONCLUSIONS: Statin therapy was associated with a reduction in MACE and all-cause mortality among participants without clinical CVD but with asymptomatic peripheral arterial disease, regardless of its low CVD risk. The absolute reduction was comparable to that achieved in secondary prevention. This project was supported by clinical research grants from the Ministerio de Salud (EC10-84, EC10-83); Spain’s Ministry of Science and Innovation through the Carlos III Health Institute, cofinanced with European Union ERDF funds (Network for Prevention and Health Promotion in primary Care RedIAPP RD12/0005, Programa HERACLES RD12/0042, and Miguel Servet Contract CP12/03287); and by the Departament de Salut, Generalitat de Catalunya, Agency for Health Technology Assessment (AATRM 034/33/02), and Agency for Management of University and Research Grants (2005SGR00577). Drs. Ramos and Garcia-Gil collaborate (without receiving any personal fee) in 2 projects of primary care for the institute IDIAP Jordi Gol funded by AstraZeneca and AMGEN that are unrelated to the present work. Dr. Marrugat has received lecture fees from Ferrer-in-Code; holds a patent with Gendiag SL; and has received payment for development of educational presentations from AstraZeneca.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. J.T. and P.H. are consultants for Servier. J.C. received research grants and honoraria from Servier. K.S. obtained research support from Boehringer Ingelheim. The remaining authors declared no competing financial interests.

Contains fulltext : 167830.pdf (Publisher’s version ) (Open Access) OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH. METHODS: We performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk. RESULTS: Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 x 10-4 ) with no heterogeneity across studies (I2 = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL-C by approximately 2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 x 10-6 ). INTERPRETATION: Genetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740.

To dissect the genetic architecture of blood pressure (BP) and assess how its elevation promotes downstream cardiovascular diseases, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry. Genotypes from an additional 140,886 individuals of European ancestry were used as validation for loci reaching genome-wide significance but without prior support in the literature. We identified 66 BP loci, of which 17 were novel and 15 harbored multiple distinct association signals, and which together explain up to 3.5% of BP variation. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in BP control through modulating blood vessel tone and fluid filtration across multiple tissues, not solely the kidney. Importantly, the 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent (South-Asian, East-Asian and African), confirming that these are ancestral physiological effects that arose prior to human migration out of Africa. The 66-SNP BP risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our data expand current knowledge of BP pathways, and also, highlight that BP regulation and its effects may occur in multiple organs and tissues beyond the classic renal system.

Objectives Epilepsy has been associated with cardiovascular comorbidity. This study aimed to assess the potential association between cardiovascular risk factors (CRFs), antiepileptic drugs (AEDs), and etiology. Material and Methods A single‐center retrospective epilepsy cohort from the decade of 2004–2013 was assessed. Poisson regression models with robust variance were estimated to obtain CRF prevalence ratios (PR) according to AED prescription and etiology. Results After excluding patients in the monotherapy group with vascular etiology or previous cardiovascular events, in the remaining 400 patients, enzyme‐inducer AEDs (EIAEDs), especially phenytoin (PHT), were associated with higher prevalence of dyslipidemia (PRa 1.77, p

BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal. METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol. FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)). INTERPRETATION: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction. FUNDING: US National Institutes of Health, The Wellcome Trust, European Union, British Heart Foundation, and the German Federal Ministry of Education and Research.