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Objective: Many studies support the notion that polygenic risk scores (PRS) improve risk prediction for coronary heart disease (CHD) beyond conventional risk factors. However, PRS are not yet considered risk-enhancing factor in guidelines. Our objective was to determine the predictive performance of a commercially available PRS (CARDIO inCode-Score®) compared with the Pooled Cohorts Equations (PCE) in a contemporary, multi-ethnic cohort. Methods: Participants (n = 63,070; 67 % female; 18 % non-European) without prior CHD were followed from 2007 through 12/31/2022. The association between the PRS and incident CHD was assessed using Cox regression adjusting for genetic ancestry and risk factors. Event rates were estimated by categories of PCE and by low/intermediate/high genetic risk within PCE categories; risk discrimination and net reclassification improvement (NRI) were also assessed. Results: There were 3,289 incident CHD events during 14 years of follow-up. Adjusted hazard ratio (aHR) for incident CHD per 1 SD increase in PRS was 1.18 (95 % CI:1.14–1.22), and the aHR for the upper vs lower quintile of the PRS was 1.66 (95 % CI:1.49–1.86). The association was consistent in both sexes, in European participants compared with all minority groups combined and was strongest in the first 5 years of follow-up. The increase in the C-statistic was 0.004 (0.747 vs. 0.751; p < 0.0001); the NRI was 2.4 (0.9–3.8) for the entire cohort and 9.7 (7.5–12.0) for intermediate PCE risk individuals. After incorporating high genetic risk, a further 10 percent of participants at borderline/intermediate PCE risk would be candidates for statin therapy. Conclusion: Inclusion of polygenic risk improved identification of primary prevention individuals who may benefit from more intensive risk factor modification.

We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease (CVD) prevention in clinical practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-Cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (Step 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After Step 1, considering proceeding to the intensified goals of Step 2 is mandatory, and this intensification will be based on 10-year CVD risk, lifetime CVD risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm—SCORE2, SCORE-OP— is recommended in these guidelines, which estimates an individual’s 10-year risk of fatal and non-fatal CVD events (myocardial infarction, stroke) in healthy men and women aged 40–89 years. Another new and important recommendation is the use of different categories of risk according different age groups (< 50, 50−69, ≥70 years).Different flow charts of CVD risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic CVD, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included. Resumen: Presentamos la adaptación española de las Guías Europeas de Prevención Cardiovascular 2021. En esta actualización además del abordaje individual, se pone mucho más énfasis en las políticas sanitarias como estrategia de prevención poblacional. Se recomienda el cálculo del riesgo vascular de manera sistemática a todas las personas adultas con algún factor de riesgo vascular. Los objetivos terapéuticos para el colesterol LDL, la presión arterial y la glucemia no han cambiado respecto a las anteriores guías, pero se recomienda alcanzar estos objetivos de forma escalonada (etapas 1 y 2). Se recomienda llegar siempre hasta la etapa 2, y la intensificación del tratamiento dependerá del riesgo a los 10 años y de por vida, del beneficio del tratamiento, de las comorbilidades, de la fragilidad y de las preferencias de los pacientes. Las guías presentan por primera vez un nuevo modelo para calcular el riesgo SCORE2 y SCORE2-OP de morbimortalidad vascular en los próximos 10 años (infarto de miocardio, ictus y mortalidad vascular) en hombres y mujeres entre 40 y 89 años. Otra de las novedades sustanciales es el establecimiento de diferentes umbrales de riesgo dependiendo de la edad (

Resumen: Presentamos la adaptación española de las Guías Europeas de Prevención Cardiovascular 2021. En esta actualización, además del abordaje individual, se pone mucho más énfasis en las políticas sanitarias como estrategia de prevención poblacional. Se recomienda el cálculo del riesgo vascular de manera sistemática a todas las personas adultas con algún factor de riesgo vascular. Los objetivos terapéuticos para el colesterol LDL, la presión arterial y la glucemia no han cambiado respecto a las anteriores guías, pero se recomienda alcanzar estos objetivos de forma escalonada (etapas 1 y 2). Se recomienda llegar siempre hasta la etapa 2, y la intensificación del tratamiento dependerá del riesgo a los 10 años y de por vida, del beneficio del tratamiento, de las comorbilidades, de la fragilidad y de las preferencias de los pacientes. Las guías presentan por primera vez un nuevo modelo para calcular el riesgo SCORE2 y SCORE2-OP de morbimortalidad vascular en los próximos 10 años (infarto de miocardio, ictus y mortalidad vascular) en hombres y mujeres entre 40 y 89 años. Otra de las novedades sustanciales es el establecimiento de diferentes umbrales de riesgo dependiendo de la edad (

AimThis study aimed to evaluate the capacity of a genetic risk score (GRS) for coronary artery disease (CAD) independent of classical cardiovascular risk factors to assess the risk of recurrence in patients with first myocardial infarction. The secondary aim was to determine the predictive value of this GRS.MethodsWe performed a meta-analysis of individual data from three studies, namely, a prospective study including 75 patients aged

ABSTRACT Introduction and objectives: Delayed vascular healing may induce late stent thrombosis. Optical coherence tomography (OCT) is useful to evaluate endothelial coverage. The objective of this study was to compare stent coverage and apposition in non-complex coronary artery lesions treated with durable polymer-coated everolimus-eluting stents (durable-polymer EES) vs biodegradable polymer-coated everolimus-eluting stents (biodegradable-polymer EES) vs polymer-free biolimus-eluting stents (BES) 1 and 6 months after stent implantation. Methods: Prospective, multicenter, non-randomized study that compared the 3 types of DES. Follow-up angiography and OCT were performed 1 and 6 months later. The primary endpoint was the rate of uncovered struts as assessed by the OCT at 1 month. Results: A total of 104 patients with de novo non-complex coronary artery lesions were enrolled. A total of 44 patients were treated with polymer-free BES, 35 with biodegradable-polymer EES, and 25 with durable-polymer EES. A high rate of uncovered struts was found at 1 month with no significant differences reported among the stents (80.2%, polymer-free BES; 88.1%, biodegradable-polymer EES; 82.5%, durable-polymer EES; P = .209). Coverage improved after 6 months in the 3 groups without significant differences being reported (97%, 95%, and 93.7%, respectively; P = .172). Conclusions: In patients with de novo non-complex coronary artery lesions treated with durable vs biodegradable vs polymer-free DES, strut coverage and apposition were suboptimal at 1 month with significant improvement at 6 months.

RESUMEN Introducción y objetivos: A pesar del desarrollo de los stents farmacoactivos, el retraso en la endotelización puede causar trombosis tardía. La tomografía de coherencia óptica puede evaluar la cobertura intimal. El objetivo de este estudio fue comparar la cobertura y la aposición en lesiones coronarias no complejas de 3 tipos de stent: stent de everolimus con polímero persistente, stent de everolimus con polímero bioabsorbible y stent de biolimus sin polímero, a 1 y 6 meses del implante. Métodos: Se diseñó un estudio prospectivo, multicéntrico, no aleatorizado, que comparó 3 stents farmacoactivos. Se realizaron angiografía y tomografía de coherencia óptica a 1 o 6 meses. El objetivo primario fue comparar la cobertura. Resultados: Se incluyeron 104 pacientes con lesiones coronarias de novo no complejas. Se implantó stent sin polímero a 44 pacientes, stent con polímero bioabsorbible a 35 pacientes y stent con polímero persistente a 25 pacientes. Al mes, se observó una alta tasa de struts no cubiertos, sin diferencias significativas entre los grupos (80,2% sin polímero, 88,1% con polímero bioabsorbible y 82,5% con polímero persistente; p = 0,209). La cobertura mejoró a los 6 meses en los 3 stents, sin diferencias significativas entre ellos (97, 95 y 93,7%, respectivamente; p = 0,172). Conclusiones: En los pacientes con lesiones coronarias no complejas tratados con stent con polímero persistente, con polímero bsorbible o sin polímero, la cobertura y la aposición fueron subóptimas a 1 mes del implante, con mejoría significativa a los 6 meses.

Abstract Familial hypercholesterolemia (FH) is an autosomal dominant disease that has a prevalence of approximately 1/250 inhabitants and is the most frequent cause of early coronary heart disease (CHD). We included 1.343.973 women and 1.210.671 men with at least one LDL-c measurement from the Catalan primary care database. We identified 14.699 subjects with Familial hypercholesterolemia-Phenotype (FH-P) based on LDL-c cut-off points by age (7.033 and 919 women, and 5.088 and 1659 men in primary and secondary prevention, respectively). Lipid lower therapy (LLT), medication possession ratio (MPR) as an indicator of adherence, and number of patients that reached their goal on lipid levels were compared by sex. In primary and secondary prevention, 69% and 54% of women (P = 0.001) and 64% and 51% of men (P = 0.001) were on low-to-moderate-potency LLT. Adherence to LLT was reduced in women older than 55 years, especially in secondary prevention (P = 0.03), where the percentage of women and men with LDL-c > 1.81 mmol/L were 99.9% and 98.9%, respectively (P = 0.001). Women with FH-P are less often treated with high-intensity LLT, less adherent to LLT, and have a lower probability of meeting their LDL-c goals than men, especially in secondary prevention.

El síndrome de Bayés es una entidad clínica que se define como la asociación entre la presencia de bloqueo interauricular avanzado (BIA-A), y el desarrollo de taquiarritmias supraventriculares (TSV), siendo la fibrilación auricular (FA), la más frecuente. Esta asociación salió a la luz con los estudios del Prof. Antoni Bayés de Luna en los años ‘80. Estudios realizados posteriormente por otros grupos encontraron una fuerte asociación entre este síndrome y la ocurrencia de fenómenos tromboembólicos, siendo el accidente cerebrovascular (ACV) el más grave. Del mismo modo, se documentó una asociación con deterioro cognitivo y demencia. Esto generó la pregunta acerca de si la terapia de anticoagulación previa a la documentación de FA podría prevenir la ocurrencia de tromboembolismos asociados al BIA-A y de esta manera preservar el estado cognitivo. Esta pregunta permanece, aún hoy, sin respuesta definitiva. Existen estudios en diferentes estadios de su desarrollo cuyo objetivo es comparar la efectividad de la anticoagulación en pacientes con BIA-A y sin FA documentada. Los resultados de los mismos permitirán establecer la efectividad de esta opción terapéutica temprana y, de manera conclusiva, definir si, para decidir anticoagular un paciente, la FA tiene que ser previamente documentada o no.

DNA methylation is dynamic, varies throughout the life course, and its levels are influenced by lifestyle and environmental factors, as well as by genetic variation. The leading genetic variants at stroke risk loci identified to date explain roughly 1–2% of stroke heritability. Most of these single nucleotide polymorphisms are situated within a regulatory sequence marked by DNase I hypersensitivity sites, which would indicate involvement of an epigenetic mechanism. To detect epigenetic variants associated with stroke occurrence and stroke subtypes. A two-stage case–control epigenome-wide association study was designed. The discovery sample with 401 samples included 218 ischaemic stroke (IS) patients, assessed at Hospital del Mar (Barcelona, Spain) and 183 controls from the REGICOR cohort. In two independent samples (N = 226 and N = 166), we replicated 22 CpG sites differentially methylated in IS in 21 loci, including 2 CpGs in locus ZFHX3, which includes known genetic variants associated with stroke. The pathways associated with these loci are inflammation and angiogenesis. The meta-analysis identified 384 differentially methylated CpGs, including loci of known stroke and vascular risk genetic variants, enriched by loci involved in lipid metabolism, adipogenesis, circadian clock, and glycolysis pathways. We identified a set of 22 CpGs in 21 loci associated with IS. Our analysis suggests that DNA methylation changes may contribute to orchestrating gene expression that contributes to IS.

[This corrects the article DOI: 10.1371/journal.pgen.1008629.].

Background Coronary artery disease remains a major cause of death despite better outcomes of ST‐segment–elevation myocardial infarction (STEMI). We aimed to analyze data from the Ruti‐STEMI registry of in‐hospital, 28‐day, and 1‐year events in patients with STEMI over the past 3 decades in Catalonia, Spain, to assess trends in STEMI prognosis. Methods and Results Between February 1989 and December 2017, a total of 7589 patients with STEMI were admitted consecutively. Patients were grouped into 5 periods: 1989 to 1994 (period 1), 1995 to 1999 (period 2), 2000 to 2004 (period 3), 2005 to 2009 (period 4), and 2010 to 2017 (period 5). We used Cox regression to compare 28‐day and 1‐year STEMI mortality and in‐hospital complication trends across these periods. Mean patient age was 61.6±12.6 years, and 79.3% were men. The 28‐day all‐cause mortality declined from period 1 to period 5 (10.4% versus 6.0%; P

The aim of this study was to determine whether genetic variants in FADS1/FADS2 and ELOVL2 are associated with overweight–obesity and body mass index (BMI) and to assess the association between these genetic variants and lipid profile and fatty acid levels. A total of 259 overweight–obese patients were compared to 369 healthy controls. FADS1 , FADS2 , and ELOVL2 genes were associated with BMI and overweight–obesity ( P ≤ .001). In an additive model, the C allele in each of these variants was associated with a lower BMI: −1.18, −0.90, and −1.23 units, respectively. Higher amounts of total cholesterol, low-density lipoprotein cholesterol, total saturated fatty acids (lauric [12:0], myristic [C14:0], palmitic [C16:0], stearic [C18:0], arachidic [20:0], lignoceric [24:0]), monounsaturated fatty acids (myristoleic [C14:1], erucic [C22:1 n-9]), and polyunsaturated fatty acids (α-linolenic [ALA, 18:3 n-3], docosahexaenoic [DHA, C22:6 n-3], eicosapentaenoic acid [EPA, C20:5n-3], arachidonic acid [AA, 20:4n-6], and conjugated linolenic acids [CLA1 and CLA2]) were shown in patients. A significant increase in D6D activities presented by 20:4n-6/18:2n-6 and 18:3n-6/18:2n-6, Δ9 desaturase (D9D) activity, estimated by the ratio 18:1n-9/18:0 and elongase activities (AE), and estimated by the ratio of docosatetraenoic/AA and DPA/EPA in patients. The C minor allele of FADS1 had significantly lower DHA. A significant decrease in stearic acid, EPA, and AE activity (docosatetraenoic/AA) was revealed in patients with the minor allele carriers of FADS2. The C minor allele of ELOVL2 had significantly lower ALA, EPA, DPA, and D6D activity (C20:4 n-6/C18:2n-6). These data suggest that variations in FADS1, FADS2, and ELOVL2 affect the risk of overweight–obesity and the level of circulating fatty acids and could point to a key molecular pathway of metabolic syndrome and its related comorbidities.

Analyzing 12,361 all-cause cirrhosis cases and 790,095 controls from eight cohorts, we identify a common missense variant in the Mitochondrial Amidoxime Reducing Component 1 gene (MARC1 p.A165T) that associates with protection from all-cause cirrhosis (OR 0.91, p = 2.3*10-11). This same variant also associates with lower levels of hepatic fat on computed tomographic imaging and lower odds of physician-diagnosed fatty liver as well as lower blood levels of alanine transaminase (-0.025 SD, 3.7*10-43), alkaline phosphatase (-0.025 SD, 1.2*10-37), total cholesterol (-0.030 SD, p = 1.9*10-36) and LDL cholesterol (-0.027 SD, p = 5.1*10-30) levels. We identified a series of additional MARC1 alleles (low-frequency missense p.M187K and rare protein-truncating p.R200Ter) that also associated with lower cholesterol levels, liver enzyme levels and reduced risk of cirrhosis (0 cirrhosis cases for 238 R200Ter carriers versus 17,046 cases of cirrhosis among 759,027 non-carriers, p = 0.04) suggesting that deficiency of the MARC1 enzyme may lower blood cholesterol levels and protect against cirrhosis.

Background Epigenome‐wide association studies for cardiometabolic risk factors have discovered multiple loci associated with incident cardiovascular disease (CVD). However, few studies have sought to directly optimize a predictor of CVD risk. Furthermore, it is challenging to train multivariate models across multiple studies in the presence of study‐ or batch effects. Methods and Results Here, we analyzed existing DNA methylation data collected using the Illumina HumanMethylation450 microarray to create a predictor of CVD risk across 3 cohorts: Women's Health Initiative, Framingham Heart Study Offspring Cohort, and Lothian Birth Cohorts. We trained Cox proportional hazards‐based elastic net regressions for incident CVD separately in each cohort and used a recently introduced cross‐study learning approach to integrate these individual scores into an ensemble predictor. The methylation‐based risk score was associated with CVD time‐to‐event in a held‐out fraction of the Framingham data set (hazard ratio per SD=1.28, 95% CI, 1.10–1.50) and predicted myocardial infarction status in the independent REGICOR (Girona Heart Registry) data set (odds ratio per SD=2.14, 95% CI, 1.58–2.89). These associations remained after adjustment for traditional cardiovascular risk factors and were similar to those from elastic net models trained on a directly merged data set. Additionally, we investigated interactions between the methylation‐based risk score and both genetic and biochemical CVD risk, showing preliminary evidence of an enhanced performance in those with less traditional risk factor elevation. Conclusions This investigation provides proof‐of‐concept for a genome‐wide, CVD‐specific epigenomic risk score and suggests that DNA methylation data may enable the discovery of high‐risk individuals who would be missed by alternative risk metrics.

Abstract We examined the clinical utility of two multi-locus genetic risk scores (GRSs) previously validated in Europeans among persons of African (AFR; n = 2,089), Latino (LAT; n = 4,349) and East-Asian (EA; n = 4,804) ancestry. We used data from the GERA cohort (30–79 years old, 68 to 73% female). We utilized two GRSs with 12 and 51 SNPs, respectively, and the Framingham Risk Score (FRS) to estimate 10-year CHD risk. After a median 8.7 years of follow-up, 450 incident CHD events were documented (95 in AFR, 316 in LAT and 39 EA, respectively). In a model adjusting for principal components and risk factors, tertile 3 vs. tertile 1 of GRS_12 was associated with 1.86 (95% CI, 1.15–3.01), 1.52 (95% CI, 1.02–2.25) and 1.19 (95% CI, 0.77–1.83) increased hazard of CHD in AFR, LAT and EA, respectively. Inclusion of the GRSs in models containing the FRS did not increase the C-statistic but resulted in net overall reclassification of 10% of AFR, 7% LAT and EA and in reclassification of 13% of AFR and EA as well as 10% LAT in the intermediate FRS risk subset. Our results support the usefulness of incorporating genetic information into risk assessment for primary prevention among minority subjects in the U.S.

Examination of predicted loss-of-function (pLOF) genetic variants allows direct identification of genes with therapeutic potential. Here, Emdin et al. perform association analysis for 3759 pLOF variants with 24 traits and highlight protective variants against cardiometabolic and immune phenotypes.

Abstract Background To evaluate the possibility of left atrial (LA) remodeling using speckle tracking echocardiography (STE) in patients with interatrial block (IAB). Methods We performed a cross-sectional study with three groups of patients: 56 without IAB, 21 with partial IAB (pIAB), and 22 with advanced IAB (aIAB). Transthoracic echocardiographic (TTE) STE was performed and clinical and echocardiographic findings were analyzed. Results TTE showed higher LA volume/body surface area in the patients with IAB. With STE, the absolute value of strain rate during atrial booster pump function (SRa) and early reservoir period (SRs) decreased in the pIAB group and even more in the aIAB group, compared to the group without IAB. The independent variables were the echocardiographic measures of LA size and function. After adjusting for confounders, both multiple linear regression and multivariate multinomial regression showed good correlation with dependent variables: longer P-wave duration on electrocardiography and with the type of IAB, respectively. SRa (p

Obesity is associated with increased risk of several diseases and has become epidemic. Obesity is highly heritable but the genetic variants identified by genome-wide association studies explain only limited variability. Epigenetics could contribute to explain the missing variability. The study aim was to discover differential methylation patterns related to obesity. We designed an epigenome-wide association study with a discovery phase in a subsample of 641 REGICOR study participants, validated by analysis of 2,515 participants in the Framingham Offspring Study. Blood DNA methylation was assessed using Illumina HumanMethylation450 BeadChip. Next, we meta-analyzed the data using the fixed effects method and performed a functional and pathway analysis using the Ingenuity Pathway Analysis software. We were able to validate 94 CpGs associated with body mass index (BMI) and 49 CpGs associated with waist circumference, located in 95 loci. In addition, we newly discovered 70 CpGs associated with BMI and 33 CpGs related to waist circumference. These CpGs explained 25.94% and 29.22% of the variability of BMI and waist circumference, respectively, in the REGICOR sample. We also evaluated 65 of the 95 validated loci in the GIANT genome-wide association data; 10 of them had Tag SNPs associated with BMI. The top-ranked diseases and functions identified in the functional and pathway analysis were neurologic, psychological, endocrine, and metabolic.

Abstract 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 ≥120 ms, 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.

Resumen: Las VI Guías Europeas de Prevención Cardiovascular recomiendan combinar las estrategias poblacional y de alto riesgo, con los cambios de estilo de vida como piedra angular de la prevención, y proponen la función SCORE para cuantificar el riesgo cardiovascular. Esta guía hace más hincapié en las intervenciones específicas de las enfermedades y las condiciones propias de las mujeres, las personas jóvenes y las minorías étnicas. No se recomienda el cribado de aterosclerosis subclínica con técnicas de imagen no invasivas. La guía establece cuatro niveles de riesgo (muy alto, alto, moderado y bajo), con objetivos terapéuticos de control lipídico según el riesgo. La diabetes mellitus confiere un riesgo alto, excepto en sujetos con diabetes tipo 2 con menos de 10 años de evolución, sin otros factores de riesgo ni complicaciones, o con diabetes tipo 1 de corta evolución sin complicaciones. La decisión de iniciar el tratamiento farmacológico de la hipertensión arterial dependerá del nivel de presión arterial y del riesgo cardiovascular, teniendo en cuenta la lesión de órganos diana. Siguen sin recomendarse los fármacos antiplaquetarios en prevención primaria por el riesgo de sangrado. La baja adherencia al tratamiento exige simplificar el régimen terapéutico e identificar y combatir sus causas. La guía destaca que los profesionales de la salud pueden ejercer un papel importante en la promoción de intervenciones poblacionales y propone medidas eficaces, tanto a nivel individual como poblacional, para promover una dieta saludable, la práctica de actividad física, el abandono del tabaquismo y la protección contra el abuso de alcohol. Abstract: 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

BACKGROUND:High-density lipoprotein (HDL) functionality and low-density lipoprotein (LDL) atherogenic traits can describe the role of both particles on cardiovascular diseases more accurately than HDL- or LDL-cholesterol levels. However, it is unclear how these lipoprotein properties are particularly affected by different cardiovascular risk factors. OBJECTIVE:To determine which lipoprotein properties are associated with greater cardiovascular risk scores and each cardiovascular risk factor. METHODS:In two cross-sectional baseline samples of PREDIMED trial volunteers, we assessed the associations of HDL functionality (N = 296) and LDL atherogenicity traits (N = 210) with: 1) the 10-year predicted coronary risk (according to the Framingham-REGICOR score), and 2) classical cardiovascular risk factors. RESULTS:Greater cardiovascular risk scores were associated with low cholesterol efflux values; oxidized, triglyceride-rich, small HDL particles; and small LDLs with low resistance against oxidation (P-trend

RESUMENLas VI Guías Europeas de Prevención Cardiovascular recomiendan combinar las estrategias poblacionales y de alto riesgo, con los cambios de estilo de vida como piedra angular de la prevención, y proponen la función SCORE para cuantificar el riesgo cardiovascular. Esta guía hace más hinca-pié en las intervenciones específicas de las enfermedades y las condiciones propias de las mujeres, las personas jóvenes y las minorías étnicas. No se re-comienda el cribado de aterosclerosis subclínica con técnicas de imagen no invasivas. La guía establece cuatro niveles de riesgo (muy alto, alto, mode-rado y bajo), con objetivos terapéuticos de control lipídico según el riesgo. La diabetes mellitus confiere un riesgo alto, excepto en sujetos con diabetes tipo 2 con menos de 10 años de evolución, sin otros factores de riesgo ni complicaciones, o con diabetes tipo 1 de corta evolución sin complicacio-nes. La decisión de iniciar el tratamiento farmacológico de la hipertensión arterial dependerá del nivel de presión arterial y del riesgo cardiovascular, teniendo en cuenta la lesión de órganos diana. Siguen sin recomendarse los fármacos antiplaquetarios en prevención primaria por el riesgo de sangrado. La baja adherencia al tratamiento exige simplificar el régimen terapéutico e identificar y combatir sus causas. La guía destaca que los profesionales de la salud pueden ejercer un papel importante en la promoción de intervenciones poblacionales y propone medidas eficaces, tanto a nivel individual como poblacional, para promover una dieta saludable, la práctica de actividad fí-sica, el abandono del tabaquismo y la protección contra el abuso de alcohol

To develop and validate a short questionnaire to estimate physical activity (PA) practice and sedentary behavior for the adult population.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).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).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.

Resumen 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.

Las guías europeas de prevención cardiovascular contemplan dos sistemas de evaluación de la evidencia (SEC y GRADE) y recomiendancombinar 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 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 PA 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 las estrategias poblacional e 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.

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.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.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.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.

Fundamentos: con el fin de disponer de una versión breve y en españoldel Cuestionario de Actividad Física en el tiempo libre de Minnesota (CAFM) para poder utilizarlo en atención primaria, el objetivo de este trabajo es presentar la elaboración de la versión reducida (VREM) y su validación. Métodos: Estudio descriptivo de validación del cuestionario, realizada en cinco centros de Atención Primaria de Barcelona. Se seleccionaron 200 sujetos igual o mayores de 50 años que consultaron por cualquier motivo, con una distribución por edad y sexo similar a la de la población de Cataluña . Dos fases: primera, se construyó el VREM mediante reducción del número de ítems. Segunda, se evaluó su validez de criterio respecto al CAFM (referencia) y la fiabilidad test-retest mediante el índice kappa y el coeficiente de correlación intraclase (CCI). Resultados: Los 6 ítems incluidos en el VREM fueron: caminar, trabajar el huerto, hacer deporte o bailar, subir escaleras, ir a comprar a pie y limpiar la casa. La duración de la entrevista mediante el VREM fue de 5 minutos (desviación estándar 2). La validez de criterio entre ambos cuestionarios, usando 4 categorías de actividad física, fue del 95,5% (kappa=0,93). La fiabilidad test-retest del cuestionario fue del 92,5% (kappa=0,88). Usando un resultado continuo en forma de metabolic energy turnover (MET) el VREM también mostró una alta validez y fiabilidad (CCI=0,95 y CCI=0,96 respectivamente). Conclusiones: La versión reducida del CAFM es válida y fiable en población mayor o igual a 50 años.

Determining overall cardiovascular risk: assessment, modeling and the goals of prevention in different social and geographic contexts RESUMEN En esta revisión narrativa se presentan los fundamentos de la prevención cardiovascular, las diferentes estrategias de prevención existentes, así como los instrumentos de estimación del riesgo cardiovascular y su implantación en la práctica clínica diaria, teniendo en cuenta la realidad asistencial de dos países como Cuba y España. Finalmente se presentan las limitaciones que tienen las funciones de riesgo cardiovascular y las líneas futuras de investigación existentes. Palabras clave: Epidemiología, factores de riesgo, funciones de riesgo, prevención de riesgo cardiovascular, riesgo coronario. ABSTRACT This narrative review describes the underlying principles of cardiovascular prevention and the various preventive strategies employed today. It also discusses the assessment instruments used to determine cardiovascular risk and their application in everyday clinical practice, while taking into account the reality of health care in two very different countries: Cuba and Spain. Finally, the limitations of cardiovascular risk functions and anticipated future directions in research are considered. Key words: Epidemiology, risk factors, risk functions, risk assessment, cardiovascular risk prevention, coronary risk.

Only a small fraction of coronary artery disease (CAD) heritability has been explained by common variants identified to date. Interactions between genes of importance to cardiovascular regulation may account for some of the missing heritability of CAD. This study aimed to investigate the role of gene-gene interactions in common variants in candidate cardiovascular genes in CAD.2,101 patients with CAD from the British Heart Foundation Family Heart Study and 2,426 CAD-free controls were included in the discovery cohort. All subjects were genotyped with the Illumina HumanCVD BeadChip enriched for genes and pathways relevant to the cardiovascular system and disease. The primary analysis in the discovery cohort examined pairwise interactions among 913 common (minor allele frequency >0.1) independent single nucleotide polymorphisms (SNPs) with at least nominal association with CAD in single locus analysis. A secondary exploratory interaction analysis was performed among all 11,332 independent common SNPs surviving quality control criteria. Replication analyses were conducted in 2,967 patients and 3,075 controls from the Myocardial Infarction Genetics Consortium. None of the interactions amongst 913 SNPs analysed in the primary analysis was statistically significant after correction for multiple testing (required P 1.7 for common variants in the primary analysis.Moderately large additive interactions between common SNPs in genes relevant to cardiovascular disease do not appear to play a major role in genetic predisposition to CAD. The role of genetic interactions amongst less common SNPs and with medium and small magnitude effects remain to be investigated.

Diet is an important factor in the prevention of chronic diseases. Analysis of secular trends of dietary patterns can be biased by energy under-reporting. Therefore, the objective of the present study was to analyse the impact of energy under-reporting on dietary patterns and secular trends in dietary patterns defined by cluster analysis.Two cross-sectional population-based surveys were conducted in Spain, in 2000 and 2005, with 3058 and 6352 participants, respectively, aged 25 to 74 years. Validated questionnaire was used to collect dietary data. Cluster analysis was run separately for all participants, plausible energy reporters (PER), and energy under-reporters (EUR) to define dietary patterns.Three clusters, "healthy", "mixed" and "western", were identified for both surveys. The "mixed" cluster was the predominant cluster in both surveys. Excluding EUR reduced the proportion of the "mixed" cluster up to 6.40% in the 2000 survey; this caused secular trend increase in the prevalence of the "mixed" pattern. Cross-classification analysis of all participants and PER' data showed substantial agreement in cluster assignments: 68.7% in 2000 and 84.4% in 2005. Excluding EUR did not cause meaningful (≥ 15%) changes in the "healthy" pattern. It provoked changes in consumption of some food groups in the "mixed" and "western" patterns: mainly decreases of unhealthy foods within the 2000 and increases of unhealthy foods within the 2005 surveys. Secular trend effects of EUR were similar to those within the 2005 survey. Excluding EUR reversed the direction of secular trends in consumption of several food groups in PER in the "mixed" and "western" patterns.EUR affected distribution of participants between dietary patterns within and between surveys, secular trends in food group consumption and amount of food consumed in all, but not in the "healthy" pattern. Our findings emphasize threats from energy under-reporting in dietary data analysis.

Genetic variation at the apolipoprotein A5 gene (APOA5) is associated with increased triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common APOA5 genetic variants with carotid IMT and stenosis. A total of 2,273 Framingham Offspring Study participants underwent carotid ultrasound and had data on at least one of the five APOA5 variants (−1131T>C, −3A>G, 56C>G, IVS3+476G >A, and 1259T>C). Although none of the individual variants was significantly associated with carotid measures, the haplotype defined by the presence of the rare allele of the 56C>G variant was associated with a higher common carotid artery (CCA) IMT compared with the wild-type haplotype (0.75 vs. 0.73 mm; P < 0.05). The rare allele of each of the −1131T >C, −3A>G, IVS3+476G>A, and 1259T>C variants and the haplotype defined by the presence of the rare alleles in these four variants were each significantly associated with CCA IMT in obese participants. These associations remained significant even after adjustment for triglycerides. APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels.

The aim of this study was to determine the association between APOE genotype and carotid atherosclerosis, defined as intimal-medial thickness (IMT) and stenosis, and to assess if other cardiovascular risk factors modify this association. A total of 1,315 men and 1,408 women from the Framingham Offspring Study underwent carotid ultrasound during examination cycle 6 and had complete data on APOE genotype. Three APOE genotype groups were defined: APOE2 (including E2/E2, E3/E2 genotypes), APOE3 (E3/E3), and APOE4 (including E4/E3, E4/E4 genotypes). Carotid IMT and the presence of carotid stenosis > 25% were determined by ultrasonography. In women, the APOE2 group was associated with lower carotid IMT (0.67 vs. 0.73 mm) and lower prevalence of stenosis (odds ratio = 0.49; 95% confidence interval = 0.30–0.81) compared with the APOE3 group. In men, APOE genotype was not associated with carotid IMT or stenosis in the whole group; however, diabetes modified the association between APOE genotype and carotid IMT (P for interaction = 0.044). Among men with diabetes, the APOE4 group was associated with a higher internal carotid artery IMT (1.22 mm) than the APOE3 group (0.90 mm) or the APOE2 group (0.84 mm).The E2 allele was associated with lower carotid atherosclerosis in women, and the E4 allele was associated with higher internal carotid IMT in diabetic men.

Regular exercise practise is a protective factor against coronary heart disease and enhances antioxidant systems, whereas acute exercise appears to be a major source of increased oxidative stress. Paraoxonase1 (PON1) is an antioxidant HDL-linked enzyme, whose activity toward paraoxon (PON1 activity) is strongly modulated by the PON1-192 polymorphism, comprising Q and R alleles for low and high PON1 activity, respectively. Another polymorphism at the PON1 locus, the PON1-55, modulates PON1 protein and activity levels. PON1 activity, lipid levels, and oxidized LDL concentration were determined in 17 healthy young volunteers before and after a 16-weeks aerobic exercise training period. Furthermore, PON1 activity was analyzed after a bout of exercise in both situations. We found that regular exercise was associated with a decrease in oxidized LDL levels, and an increase in PON1 activity in QQ subjects and with a decrease in PON1 activity in R carriers. A bout of exercise produced an increase in PON1 activity just after the bout of exercise, followed by a decrease in its activity. A recovery of the basal PON1 activity levels at 24 h was found in QQ subjects regardless of their training status and in trained R carriers, but not in untrained R carriers. These results suggest that the effects of regular and acute exercise on PON1 activity levels are modulated by PON1-192 polymorphism. Changes were less evident for the PON1-55 polymorphism.—Tomás, M., R. Elosua, M. Sentí, L. Molina, J. Vila, R. Anglada, M. Fitó, M. I. Covas, J. Marrugat. PON1-192 polymorphism modulates the effects of regular and acute exercise on paraoxonase1 activity. J. Lipid Res. 2002. 43: 713–720.

BackgroundStudies of associations between plasma GSH-Px activity and cardiovascular risk factors have been done in humans, and contradictory results have been reported. The aim of our study was to assess the association between the scavenger antioxidant enzyme glutathione peroxidase (GSH-Px) activity in plasma and the presence of novel and classical cardiovascular risk factors in elderly patients.MethodsWe performed a cross-sectional study with baseline data from a subsample of the PREDIMED (PREvención con DIeta MEDiterránea) study in Spain. Participants were 1,060 asymptomatic subjects at high risk for cardiovascular disease (CVD), aged 55 to 80, selected from 8 primary health care centers (PHCCs). We assessed classical CVD risk factors, plasma oxidized low-density lipoproteins (ox-LDL), and glutathione peroxidase (GSH-Px) using multilevel statistical procedures.ResultsMean GSH-Px value was 612 U/L (SE: 12 U/L), with variation between PHCCs ranging from 549 to 674 U/L (Variance = 013.5; PConclusionIn a population at high cardiovascular risk, a positive linear association was observed between plasma GSH-Px activity and both glucose and ox-LDL levels. The high GSH-Px activity observed when an oxidative stress situation occurred, such as hyperglycemia and lipid oxidative damage, could be interpreted as a healthy defensive response against oxidative injury in our cardiovascular risk population.

Ischemic stroke (IS), a heterogeneous multifactorial disorder, is among the leading causes of mortality and long-term disability in the western world. Epidemiological data provides evidence for a genetic component to the disease, but its epigenetic involvement is still largely unknown. Epigenetic mechanisms, such as DNA methylation, change over time and may be associated with aging processes and with modulation of the risk of various pathologies, such as cardiovascular disease and stroke. We analyzed 2 independent cohorts of IS patients. Global DNA methylation was measured by luminometric methylation assay (LUMA) of DNA blood samples. Univariate and multivariate regression analyses were used to assess the methylation differences between the 3 most common IS subtypes, large-artery atherosclerosis (LAA), small-artery disease (SAD), and cardio-aortic embolism (CE). A total of 485 IS patients from 2 independent hospital cohorts (n = 281 and n = 204) were included, distributed across 3 IS subtypes: LAA (78/281, 59/204), SAD (97/281, 53/204), and CE (106/281, 89/204). In univariate analyses, no statistical differences in LUMA levels were observed between the 3 etiologies in either cohort. Multivariate analysis, adjusted by age, sex, hyperlipidemia, and smoking habit, confirmed the lack of differences in methylation levels between the analyzed IS subtypes in both cohorts. Despite differences in pathogenesis, our results showed no global methylation differences between LAA, SAD, and CE subtypes of IS. Further work is required to establish whether the epigenetic mechanism of methylation might play a role in this complex disease.

Background and objectiveCoronary heart disease (CHD) is the leading cause of death, and smoking its strongest modifiable risk factor. Our aim was to determine the impact of the Spanish 2006 partial smoke-free legislation on acute myocardial infarction (AMI) incidence, hospitalization and mortality rates, and 28-day case-fatality in Girona, Spain.MethodsUsing a population-based registry (the REGICOR Study), we compared population incidence, hospitalization, and mortality rates, and 28-day case-fatality in the pre- and post-ban periods (2002-2005 and 2006-2008, respectively) by binomial regression analysis adjusted for confounding factors. We also analyzed the ban's impact on the outcomes of interest using the AMI definitions of the American Heart Association (AHA)/European Society of Cardiology (ESC) and the World Health Organization (WHO)-Monitoring trends and determinants in cardiovascular diseases (MONICA).ResultsIn the post-ban period, AMI incidence and mortality rates significantly decreased (relative risk [RR] = 0.89; 95% confidence interval [CI] = 0.81-0.97 and RR = 0.82; 95% CI = 0.71-0.94, respectively). Incidence and mortality rates decreased in both sexes, especially in women, and in people aged 65-74 years. Former and non-smokers (passive smokers) showed diminished incidence rates. Implementation of the ban was not associated with AMI case-fatality. Models tended to be more significant with the WHO-MONICA than with the AHA/ESC definition.ConclusionsThe 2006 Spanish partial smoke-free legislation was associated with a decrease in population AMI incidence and mortality, particularly in women, in people aged 65-74 years, and in passive smokers. These results clarify the association between AMI mortality and the enactment of a partial smoke-free legislation and reinforce the effectiveness of smoking regulations in preventing CHD.

In DNA methylation, methyl groups are covalently bound to CpG dinucleotides. However, the assumption that methyl groups are not lost during routine DNA extraction has not been empirically tested. To avoid nonbiological associations in DNA methylation studies, it is essential to account for potential batch effect bias in the assessment of this epigenetic mechanism. Our purpose was to determine if the DNA isolation method is an independent source of variability in methylation status. We quantified Global DNA Methylation (GDM) by luminometric methylation assay (LUMA), comparing the results from 3 different DNA isolation methods. In the controlled analysis (n = 9), GDM differed slightly for the same individual depending on extraction method. In the population analysis (n = 580) there were significant differences in GDM between the 3 DNA isolation methods (medians, 78.1%, 76.5% and 75.1%; p

The genetic loci that have been found by genome-wide association studies to modulate risk of coronary heart disease explain only a fraction of its total variance, and gene-gene interactions have been proposed as a potential source of the remaining heritability. Given the potentially large testing burden, we sought to enrich our search space with real interactions by analyzing variants that may be more likely to interact on the basis of two distinct hypotheses: a biological hypothesis, under which MI risk is modulated by interactions between variants that are known to be relevant for its risk factors; and a statistical hypothesis, under which interacting variants individually show weak marginal association with MI. In a discovery sample of 2,967 cases of early-onset myocardial infarction (MI) and 3,075 controls from the MIGen study, we performed pair-wise SNP interaction testing using a logistic regression framework. Despite having reasonable power to detect interaction effects of plausible magnitudes, we observed no statistically significant evidence of interaction under these hypotheses, and no clear consistency between the top results in our discovery sample and those in a large validation sample of 1,766 cases of coronary heart disease and 2,938 controls from the Wellcome Trust Case-Control Consortium. Our results do not support the existence of strong interaction effects as a common risk factor for MI. Within the scope of the hypotheses we have explored, this study places a modest upper limit on the magnitude that epistatic risk effects are likely to have at the population level (odds ratio for MI risk 1.3-2.0, depending on allele frequency and interaction model).