Blood DNA methylation signature of diet quality and association with cardiometabolic traits.

AIMS: Diet quality might influence cardiometabolic health through epigenetic changes, but this has been little investigated in adults. Our aims were to identify cytosine-phosphate-guanine (CpG) dinucleotides associated with diet quality by conducting an epigenome-wide association study (EWAS) based on blood DNA methylation (DNAm) and to assess how diet-related CpGs associate with inherited susceptibility to cardiometabolic traits: body mass index (BMI), systolic blood pressure (SBP), triglycerides, type 2 diabetes (T2D), and coronary heart disease (CHD). METHODS AND RESULTS: Meta-EWAS including 5274 participants in four cohorts from Spain, the USA, and the UK. We derived three dietary scores (exposures) to measure adherence to a Mediterranean diet, to a healthy plant-based diet, and to the Dietary Approaches to Stop Hypertension. Blood DNAm (outcome) was assessed with the Infinium arrays Human Methylation 450K BeadChip and MethylationEPIC BeadChip. For each diet score, we performed linear EWAS adjusted for age, sex, blood cells, smoking and technical variables, and BMI in a second set of models. We also conducted Mendelian randomization analyses to assess the potential causal relationship between diet-related CpGs and cardiometabolic traits. We found 18 differentially methylated CpGs associated with dietary scores (P < 1.08 × 10-7; Bonferroni correction), of which 12 were previously associated with cardiometabolic traits. Enrichment analysis revealed overrepresentation of diet-associated genes in pathways involved in inflammation and cardiovascular disease. Mendelian randomization analyses suggested that genetically determined methylation levels corresponding to lower diet quality at cg02079413 (SNORA54), cg02107842 (MAST4), and cg23761815 (SLC29A3) were causally associated with higher BMI and at cg05399785 (WDR8) with greater SBP, and methylation levels associated with higher diet quality at cg00711496 (PRMT1) with lower BMI, T2D risk, and CHD risk and at cg0557921 (AHRR) with lower CHD risk. CONCLUSION: Diet quality in adults was related to differential methylation in blood at 18 CpGs, some of which related to cardiometabolic health.

We conducted a study to investigate the connection between diet quality, epigenetic changes, and cardiovascular health in adults. The study included 5274 participants from Spain, the USA, and the UK, combining data from four different cohorts. We assessed adherence to different healthy diets: Mediterranean style diet, plant-based diet, and Dietary Approaches to Stop Hypertension diet. We used advanced technology to analyse blood DNA methylation, which refers to chemical modifications in the DNA that can affect gene activity.We discovered 18 CpGs that showed differential methylation patterns related to the dietary scores. Importantly, 12 of these CpGs had previously been associated with cardiovascular disease or risk factors, suggesting a potential link between diet, epigenetic changes, and heart health. Some of the diet-related CpGs mapped to genes involved in pathways associated with cardiovascular disease. Moreover, using a method called Mendelian randomization, we found that several CpGs may have a causal association with body mass index, systolic blood pressure, and risk of type 2 diabetes and coronary heart disease.

Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention.

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.

Women with familial hypercholesterolemia phenotype are undertreated and poorly controlled compared to men.

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.

Cholesterol and Hypertension Treatment Improve Coronary Risk Prediction but Not Time-Dependent Covariates or Competing Risks.

Background and Aims: Cardiovascular (CV) risk functions are the recommended tool to identify high-risk individuals. However, their discrimination ability is not optimal. While the effect of biomarkers in CV risk prediction has been extensively studied, there are no data on CV risk functions including time-dependent covariates together with other variables. Our aim was to examine the effect of including time-dependent covariates, competing risks, and treatments in coronary risk prediction. Methods: Participants from the REGICOR population cohorts (North-Eastern Spain) aged 35-74 years without previous history of cardiovascular disease were included (n = 8470). Coronary and stroke events and mortality due to other CV causes or to cancer were recorded during follow-up (median = 12.6 years). A multi-state Markov model was constructed to include competing risks and time-dependent classical risk factors and treatments (2 measurements). This model was compared to Cox models with basal measurement of classical risk factors, treatments, or competing risks. Models were cross-validated and compared for discrimination (area under ROC curve), calibration (Hosmer-Lemeshow test), and reclassification (categorical net reclassification index). Results: Cancer mortality was the highest cumulative-incidence event. Adding cholesterol and hypertension treatment to classical risk factors improved discrimination of coronary events by 2% and reclassification by 7-9%. The inclusion of competing risks and/or 2 measurements of risk factors provided similar coronary event prediction, compared to a single measurement of risk factors. Conclusion: Coronary risk prediction improves when cholesterol and hypertension treatment are included in risk functions. Coronary risk prediction does not improve with 2 measurements of covariates or inclusion of competing risks.

Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention. / Comentario del CEIPV a las nuevas Guías Europeas de Prevención Cardiovascular 2021.

We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease 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 cardiovascular disease 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 (steps 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 cardiovascular disease risk, lifetime cardiovascular disease risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm ?SCORE2, SCORE2-OP? is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal cardiovascular disease 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 to different age groups (<50, 50-69, ≥70 years). Different flow charts of cardiovascular disease risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic cardiovascular disease, 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.

[Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention.] / Comentario del CEIPV a las nuevas Guías Europeas de Prevención Cardiovascular 2021.

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.

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 (<50, 50-69, >70 años). Se presentan diferentes algoritmos de cálculo del riesgo vascular y tratamiento de los factores de riesgo vascular para personas aparentemente sanas, pacientes con diabetes y pacientes con enfermedad vascular aterosclerótica. Los pacientes con enfermedad renal crónica se considerarán de riesgo alto o muy alto según la tasa del filtrado glomerular y el cociente albúmina/creatinina. Se incluyen innovaciones en las recomendaciones sobre los estilos de vida, adaptadas a las recomendaciones del Ministerio de Sanidad, así como aspectos novedosos relacionados con el control de los lípidos, la presión arterial, la diabetes y la insuficiencia renal crónica.

High cardiovascular risk in older patients with opioid use disorder: Differences with the general population.

INTRODUCTION: Cardiovascular disease is a health concern in ageing population with opioid use disorders (OUD). The study aims to analyse the cardiovascular risk factors in individuals with OUD. METHODS: An observational study was carried out to compare cardiovascular risk factors of adults >50 years with OUD on methadone therapy from public outpatient drug treatment centres, with that of an age- and gender-matched sample (ratio of 1:5) of subjects from a sample of the Spanish population (REGICOR cohort). High cardiovascular risk (HCVR) at 10 years was defined according to Framingham-REGICOR and SCORE risk functions. RESULTS: The individuals studied included 94 people with OUD and 495 from the general population; the mean age was 55.7 ± 4.8 years and 432 (72.7%) were men. Obesity (21.2% vs. 35.2%), hypertension (26.3% vs. 42.1%), total cholesterol (30.3% vs. 65.4%) and LDL-cholesterol ≥130 mg/dL (27.2% vs. 59.3%) were significantly more prevalent in the general population group, while tobacco smoking (96.0% vs. 25.9%), low HDL-cholesterol (46.5% vs. 21.2%), hypertriglyceridaemia (39.4% vs. 18.8%) and atherogenic dyslipidaemia (30.3% vs. 10.5%) were significantly higher in individuals with OUD. Differences in abdominal obesity (62.6% vs. 65.3%) were not significant. HCVR was more prevalent in patients with OUD: 15.2% versus 5.8% (Framingham-REGICOR function) and 21.2% versus 11.3% (SCORE function). DISCUSSION AND CONCLUSIONS: Older adults with OUD on methadone therapy have a different prevalence of cardiovascular risk factors and HCVR than the general population. Preventive measures, particularly tobacco smoking cessation and weight control, should be included in the routine care of individuals with OUD.

Predictive Value of Complete Blood Count-Derived Inflammatory Markers for 5-Year Survival After Carotid Endarterectomy: Implications for Practice.

Complete blood count inflammatory markers (CBC-IMs) have been associated with cardiovascular diseases and mortality. We aimed to evaluate the relationship between preoperative CBC-IMs and 5-year survival after carotid endarterectomy (CEA). Retrospective analysis of 411 consecutive patients who underwent CEA between 2004 and 2018 was done. CBC-IM included the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte (LMR) ratio, and systemic immune-inflammation index (SII). Survival rate at 5 years was 79.8%. Age (hazard ratio (HR) = 1.05, P = .003), hemoglobin (HR = 0.78, P < .001), heart failure (HR = 2.91, P = .005), American Society of Anesthesiologists (ASA)-IV score (HR = 2.41, P = .043), and active neoplastic disease (HR = 2.61, P = .028) were independently related to survival. The discrimination of this model (C-statistic) was 0.698. Spline analysis showed a linear relationship between survival and NLR (P < .001), PLR (P < .001), and SII (P < .001). After adjusting for the baseline predictive score, there was a significant relationship between survival and NLR (HR = 1.191, P = .001), PLR (HR = 1.004, P = .017), and SII (HR = 1.001, P < .001). The addition of NLR, PLR, and SII to the survival model improved the continuous net reclassification index (c-NRI) by 0.29 (P = .028), 0.347 (P = .008), and 0.481 (P < .001), respectively, but not the C-statistic. CBC-IMs show a linear and independent relationship with 5-year survival after CEA and may moderately contribute to patient selection for this preventive intervention.

DNA methylation and gene expression integration in cardiovascular disease.

BACKGROUND: The integration of different layers of omics information is an opportunity to tackle the complexity of cardiovascular diseases (CVD) and to identify new predictive biomarkers and potential therapeutic targets. Our aim was to integrate DNA methylation and gene expression data in an effort to identify biomarkers related to cardiovascular disease risk in a community-based population. We accessed data from the Framingham Offspring Study, a cohort study with data on DNA methylation (Infinium HumanMethylation450 BeadChip; Illumina) and gene expression (Human Exon 1.0 ST Array; Affymetrix). Using the MOFA2 R package, we integrated these data to identify biomarkers related to the risk of presenting a cardiovascular event. RESULTS: Four independent latent factors (9, 19, 21-only in women-and 27), driven by DNA methylation, were associated with cardiovascular disease independently of classical risk factors and cell-type counts. In a sensitivity analysis, we also identified factor 21 as associated with CVD in women. Factors 9, 21 and 27 were also associated with coronary heart disease risk. Moreover, in a replication effort in an independent study three of the genes included in factor 27 were also present in a factor identified to be associated with myocardial infarction (CDC42BPB, MAN2A2 and RPTOR). Factor 9 was related to age and cell-type proportions; factor 19 was related to age and B cells count; factor 21 pointed to human immunodeficiency virus infection-related pathways and inflammation; and factor 27 was related to lifestyle factors such as alcohol consumption, smoking and body mass index. Inclusion of factor 21 (only in women) improved the discriminative and reclassification capacity of the Framingham classical risk function and factor 27 improved its discrimination. CONCLUSIONS: Unsupervised multi-omics data integration methods have the potential to provide insights into the pathogenesis of cardiovascular diseases. We identified four independent factors (one only in women) pointing to inflammation, endothelium homeostasis, visceral fat, cardiac remodeling and lifestyles as key players in the determination of cardiovascular risk. Moreover, two of these factors improved the predictive capacity of a classical risk function.

DNA methylation biomarkers of myocardial infarction and cardiovascular disease.

BACKGROUND: The epigenetic landscape underlying cardiovascular disease (CVD) is not completely understood and the clinical value of the identified biomarkers is still limited. We aimed to identify differentially methylated loci associated with acute myocardial infarction (AMI) and assess their validity as predictive and causal biomarkers. RESULTS: We designed a case-control, two-stage, epigenome-wide association study on AMI (ndiscovery = 391, nvalidation = 204). DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. We performed a fixed-effects meta-analysis of the two samples. 34 CpGs were associated with AMI. Only 12 of them were available in two independent cohort studies (n ~ 1800 and n ~ 2500) with incident coronary and cardiovascular disease (CHD and CVD, respectively). The Infinium HumanMethylation450 BeadChip was used in those two studies. Four of the 12 CpGs were validated in association with incident CHD: AHRR-mapping cg05575921, PTCD2-mapping cg25769469, intergenic cg21566642 and MPO-mapping cg04988978. We then assessed whether methylation risk scores based on those CpGs improved the predictive capacity of the Framingham risk function, but they did not. Finally, we aimed to study the causality of those associations using a Mendelian randomization approach but only one of the CpGs had a genetic influence and therefore the results were not conclusive. CONCLUSIONS: We have identified 34 CpGs related to AMI. These loci highlight the relevance of smoking, lipid metabolism, and inflammation in the biological mechanisms related to AMI. Four were additionally associated with incident CHD and CVD but did not provide additional predictive information.

Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Cardiovascular Prevention Guidelines. / Comentario del CEIPV a la actualización de las Guías Europeas de Prevención Vascular en la Práctica Clínica.

We present the adaptation for Spain of the updated European Cardiovascular Prevention Guidelines. In this update, greater stress is laid on the population approach, and especially on the promotion of physical activity and healthy diet through dietary, leisure and active transport policies in Spain. To estimate vascular risk, note should be made of the importance of recalibrating the tables used, by adapting them to population shifts in the prevalence of risk factors and incidence of vascular diseases, with particular attention to the role of chronic kidney disease. At an individual level, the key element is personalised support for changes in behaviour, adherence to medication in high-risk individuals and patients with vascular disease, the fostering of physical activity, and cessation of smoking habit. Furthermore, recent clinical trials with PCSK9 inhibitors are reviewed, along with the need to simplify pharmacological treatment of arterial hypertension to improve control and adherence to treatment. In the case of patients with type 2 diabetes mellitus and vascular disease or high vascular disease risk, when lifestyle changes and metformin are inadequate, the use of drugs with proven vascular benefit should be prioritised. Lastly, guidelines on peripheral arterial disease and other specific diseases are included, as is a recommendation against prescribing antiaggregants in primary prevention.

[Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Cardiovascular Prevention Guidelines]. / Comentario del CEIPV a la actualización de las Guías Europeas de Prevención Vascular en la Práctica Clínica.

We present the adaptation for Spain of the updated European Cardiovascular Prevention Guidelines. In this update, greater stress is laid on the population approach, and especially on the promotion of physical activity and healthy diet through dietary, leisure and active transport policies in Spain. To estimate vascular risk, note should be made of the importance of recalibrating the tables used, by adapting them to population shifts in the prevalence of risk factors and incidence of vascular diseases, with particular attention to the role of chronic kidney disease. At an individual level, the key element is personalised support for changes in behaviour, adherence to medication in high-risk individuals and patients with vascular disease, the fostering of physical activity, and cessation of smoking habit. Furthermore, recent clinical trials with PCSK9 inhibitors are reviewed, along with the need to simplify pharmacological treatment of arterial hypertension to improve control and adherence to treatment. In the case of patients with type 2 diabetes mellitus and vascular disease or high vascular disease risk, when lifestyle changes and metformin are inadequate, the use of drugs with proven vascular benefit should be prioritised. Lastly, guidelines on peripheral arterial disease and other specific diseases are included, as is a recommendation against prescribing antiaggregants in primary prevention.

[Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Cardiovascular Prevention Guidelines.] / Comentario del CEIPV a la actualización de las Guías Europeas de Prevención Vascular en la Práctica Clínica.

We present the adaptation for Spain of the updated European Cardiovascular Prevention Guidelines. In this update, greater stress is laid on the population approach, and especially on the promotion of physical activity and healthy diet through dietary, leisure and active transport policies in Spain. To estimate vascular risk, note should be made of the importance of recalibrating the tables used, by adapting them to population shifts in the prevalence of risk factors and incidence of vascular diseases, with particular attention to the role of chronic kidney disease. At an individual level, the key element is personalised support for changes in behaviour, adherence to medication in high-risk individuals and patients with vascular disease, the fostering of physical activity, and cessation of smoking habit. Furthermore, recent clinical trials with PCSK9 inhibitors are reviewed, along with the need to simplify pharmacological treatment of arterial hypertension to improve control and adherence to treatment. In the case of patients with type 2 diabetes mellitus and vascular disease or high vascular disease risk, when lifestyle changes and metformin are inadequate, the use of drugs with proven vascular benefit should be prioritised. Lastly, guidelines on peripheral arterial disease and other specific diseases are included, as is a recommendation against prescribing antiaggregants in primary prevention.

Presentamos la adaptación para España de la actualización de las Guías Europeas de Prevención Vascular. En esta actualización se hace mayor énfasis en el abordaje poblacional, especialmente en la promoción de la actividad física y de una dieta saludable mediante políticas alimentarias y de ocio y transporte activo en España. Para estimar el riesgo vascular, se destaca la importancia de recalibrar las tablas que se utilicen, adaptándolas a los cambios poblaciones en la prevalencia de los factores de riesgo y en la incidencia de enfermedades vasculares, con particular atención al papel de la enfermedad renal crónica. A nivel individual resulta clave el apoyo personalizado para el cambio de conducta, la adherencia a la medicación en los individuos de alto riesgo y pacientes con enfermedad vascular, la promoción de la actividad física y el abandono del hábito tabáquico. Además, se revisan los ensayos clínicos recientes con inhibidores de PCKS9, la necesidad de simplificar el tratamiento farmacológico de la hipertensión arterial para mejorar su control y la adherencia al tratamiento. En los pacientes con diabetes mellitus 2 y enfermedad vascular o riesgo vascular alto, cuando los cambios de estilo de vida y la metformina resultan insuficientes, deben priorizarse los fármacos con demostrado beneficio vascular. Por último, se incluyen pautas sobre enfermedad arterial periférica y otras enfermedades específicas, y se recomienda no prescribir antiagregantes en prevención primaria.

Transitioning from a coronary to a critical cardiovascular care unit: trends over the past three decades.

BACKGROUND: Coronary care units were established in the 1960s to reduce acute-phase mortality in acute coronary syndrome. In the 21st century, the original coronary care unit concept has evolved into an intensive cardiovascular care unit. The aim of this study was to analyse trend changes in characteristics and mortality of patients admitted to a coronary care unit over the past three decades. METHOD: Between February 1989 and December 2017, a total of 18,334 patients was consecutively admitted to the coronary care unit of a university hospital in Barcelona. Data were analysed in five time frames: 1989-1994, 1995-1999, 2000-2004, 2005-2009 and 2010-2017. We analysed demographic profile, diagnoses at admission and trend changes in mortality across periods. RESULTS: During the periods, the patients' ages and comorbidities increased. Diagnoses at admission have evolved. Acute coronary syndrome cases declined from the first to the last period (72.6% vs. 62.8%) while heart failure (6.0% vs. 8.6%) and malignant arrhythmias (0.8% vs. 4.0%) increased significantly. Overall, coronary care unit mortality decreased 34% from the first to the last period (6.8% vs. 4.5%, P<0.001). Furthermore, the cause of death has changed, those due to acute coronary syndrome declining (66.7% vs. 45.5%), and death from malignant arrhythmias increasing (1.9% vs. 16.2%) from the first to the last period. CONCLUSIONS: Although acute coronary syndrome remained the main diagnosis, heart failure and arrhythmias have increased. Despite the aging and comorbidities, overall mortality in the coronary care unit decreased by 34% in the past three decades. Deaths due to acute coronary syndrome have declined, whereas those due to malignant arrhythmias have increased.

DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues.

BACKGROUND AND PURPOSE: Polymorphisms and serum levels of Matrix Metalloproteinases (MMP) and Tissue Inhibitor of Metalloproteinases (TIMP) have been studied with regard to atheromatous plaques and ischemic stroke, while no studies of DNA methylation (DNAm) patterns of MMP or TIMP have been performed to that end. Here, we evaluate DNAm levels of the MMP and TIMP gene families in human carotid plaques and blood samples of atherothrombotic stroke patients. METHODS: We profiled the DNAm status of stable and ulcerated atherosclerotic plaques obtained as pair sets from three patients who underwent carotid endarterectomy surgery. We selected 415 CpG sites, mapping into MMPs and TIMPs genes for further study. Secondly, the statistically associated CpG sites were analyzed in blood samples from two separate atherothrombotic stroke cohorts (total sample size = 307), ischemic stroke-cohort 1 (ISC-1): 37 atherothrombotic patients and 6 controls, ischemic stroke-cohort 2 (ISC-2): 80 atherothrombotic patients and 184 controls. DNAm levels from plaque tissue and blood samples were evaluated using a high-density microarray Infinium, HumanMethylation450 BeadChip and Infinium MethylationEPIC BeadChip. RESULTS: Three CpG sites were statistically significantly associated with unstable plaque portions; cg02969624, q-value = 0.035 (TIMP2), and cg04316754, q-value = 0.037 (MMP24) were hypermethylated, while cg24211657 q-value = 0.035 (TIMP2) was hypomethylated. Association of cg04316754 (MMP24) methylation levels with atherothrombotic risk was also observed in blood tissue: ISC-1 p-values = 0.03, ISC-2 p-value = 1.9 × 10-04. CONCLUSIONS: The results suggest different DNAm status of MMP24 between stable and unstable atherothrombotic carotid plaques, and between atherothrombotic stroke and controls in blood samples.

Transitioning from a coronary to a critical cardiovascular care unit: trends over the past three decades.

BACKGROUND: Coronary care units were established in the 1960s to reduce acute-phase mortality in acute coronary syndrome. In the 21st century, the original coronary care unit concept has evolved into an intensive cardiovascular care unit. The aim of this study was to analyse trend changes in characteristics and mortality of patients admitted to a coronary care unit over the past three decades. METHOD: Between February 1989 and December 2017, a total of 18,334 patients was consecutively admitted to the coronary care unit of a university hospital in Barcelona. Data were analysed in five time frames: 1989-1994, 1995-1999, 2000-2004, 2005-2009 and 2010-2017. We analysed demographic profile, diagnoses at admission and trend changes in mortality across periods. RESULTS: During the periods, the patients' ages and comorbidities increased. Diagnoses at admission have evolved. Acute coronary syndrome cases declined from the first to the last period (72.6% vs. 62.8%) while heart failure (6.0% vs. 8.6%) and malignant arrhythmias (0.8% vs. 4.0%) increased significantly. Overall, coronary care unit mortality decreased 34% from the first to the last period (6.8% vs. 4.5%, P<0.001). Furthermore, the cause of death has changed, those due to acute coronary syndrome declining (66.7% vs. 45.5%), and death from malignant arrhythmias increasing (1.9% vs. 16.2%) from the first to the last period. CONCLUSIONS: Although acute coronary syndrome remained the main diagnosis, heart failure and arrhythmias have increased. Despite the aging and comorbidities, overall mortality in the coronary care unit decreased by 34% in the past three decades. Deaths due to acute coronary syndrome have declined, whereas those due to malignant arrhythmias have increased.