Polygenic risk and incident coronary heart disease in a large multiethnic cohort.

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.

Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbab le, gut-restricted adsorbent in models and patients with cirrhosis.

OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER: NCT03202498.

Rigidez carotídea y riesgo de eventos vasculares y mortalidad: el estudio REGICOR / Carotid artery stiffness and risk of vascular events and mortality: the REGICOR study

Introducción y objetivos: Los objetivos son analizar la relación dosis-respuesta de la rigidez de la arteria carótida y la mortalidad y evaluar su capacidad predictiva. Métodos: Estudio de cohorte poblacional que incluyó a 6.468 participantes, con una mediana de seguimiento de 6,5 años. Se evaluaron 6 índices de rigidez. Se identificaron los eventos coronarios y cerebrovasculares y la mortalidad. Resultados: La rigidez carotídea, el coeficiente de Peterson y la velocidad de la onda de pulso (VOP) se asociaron de manera lineal y directa con los eventos cerebrovasculares: aumento del 8% (IC95%, 1-16%) por unidad de rigidez, del 7% (IC95%, 2-13%) cada 10 unidades del coeficiente de Peterson y del 26% (IC95%, 8-48%) por unidad de la VOP. La tensión carotídea se asoció de modo no lineal con el riesgo de enfermedad coronaria: en valores <0,09 unidades, cada aumento de 0,01 unidades se asoció con una disminución de un 16% del riesgo (IC95%, –33 a +6%); por encima de 0,09 unidades, cada incremento de 0,01 unidades se asoció con un aumento de un 16% del riesgo (IC95%, 6-27%). La inclusión de estos índices no mejoró la capacidad predictiva de las funciones de riesgo. Conclusiones: La rigidez carotídea, el coeficiente de elasticidad de Peterson y la VOP tienen una relación lineal y directa con el riesgo de enfermedad cerebrovascular. La tensión (strain) carotídea tiene una relación en U con el riesgo de enfermedad coronaria. Estos índices no contribuyen a mejorar la capacidad predictiva de las funciones de riesgo. (AU)

Introduction and objectives: The aims of this study were to determine the dose-response association of carotid arterial stiffness with vascular outcomes and overall mortality, and to assess their added predictive capacity. Methods: Population-based cohort study including 6468 individuals, with a median follow-up of 6.5 years. Six carotid artery stiffness indices were assessed: strain, stiffness, Peterson elasticity coefficient, compliance coefficient, distensibility coefficient, and pulse wave velocity (PWV). Incident coronary, cerebrovascular, global vascular, and total fatal events were identified. Results: Carotid compliance and distensibility coefficients were not associated with any of the outcomes. Carotid stiffness, Peterson elasticity coefficient, and PWV showed a direct linear relationship to cerebrovascular disease: the risk increased by 8% (95%CI, 1-16) per stiffness unit increase, by 7% (95%CI, 2-13) per 10-unit Peterson elasticity coefficient increase, and by 26% (95%CI, 8-48) per PWV unit increase. Carotid strain showed a nonlinear association with ischemic heart disease. When strain was ≤ 0.09 units, each 0.01-unit increase was associated with a 15% lower risk of coronary events (95%CI,−33 to 6); above 0.09 units, each 0.01 increase in strain was associated with a 16% higher risk of coronary events (95%CI, 6-27). The addition of the stiffness indices did not improve the predictive capacity of validated risk functions. Conclusions: Carotid stiffness, Peterson elasticity coefficient, and PWV have a direct linear association with cerebrovascular disease risk. Carotid strain is not linearly related to U-shaped ischemic heart disease risk. The inclusion of these indexes does not improve the predictive capacity of risk functions. (AU)

Documento de consenso de la Sociedad Española de Obstetricia y Ginecologia (SEGO)y el Comité Español Interdisciplinario para la Prevención Vascular (CEIPV). Ventanade oportunidad: prevención del riesgo vascular en la mujer. Resultados adversos delembarazo y riesgo de enfermedad vascular* / Consensus document from the Spanish Society of Obstetrics and Gynecology (SEGO) and the Spanish Interdisciplinary Committee for Vascular Prevention (CEIPV). Window of opportunity: vascular risk prevention in women. Adverse pregnancy outcomes and risk of vascular diseas

Este documento resume la evidencia que existe entre los resultados adversos del embarazo (RAE) y el riesgo que tiene una persona gestante de desarrollar factores de riesgo vascular (RV) que pueden terminar provocando enfermedad vascular (EV) futura. Asimismo, este documento destaca la importancia de saber reconocer los RAE cuando se evalúa el RV en mujeres. Un antecedente de RAE es un indicador suficiente para hacer una prevención primaria de EV. De hecho, adoptar una dieta saludable y aumentar la actividad física entre las mujeres con RAE, de inicio en el embarazo o en el posparto y manteniéndolas a lo largo de la vida, son intervenciones importantes que permiten disminuir el RV. Por otro lado, la lactancia materna también puede disminuir el RV posterior de la mujer, incluyendo menos riesgo de mortalidad. Estudios futuros que evalúen el uso del ácido acetilsalicílico, las estatinas y la metformina, entre otros, en las mujeres con antecedentes de RAE podrían reforzar las recomendaciones sobre el uso de la farmacoterapia en la prevención primaria de la EV entre estas pacientes. Existen diferentes opciones dentro de los sistemas de salud para mejorar la transición de la atención de las mujeres con RAE entre los diferentes profesionales e implementar estrategias para reducir su RV a largo plazo. Una posible estrategia podría ser la incorporación del concepto del cuarto trimestre en las recomendaciones clínicas y las políticas de atención de la salud.(AU)

This document summarises the evidence regarding the association between adverse pregnancy outcomes (APOs),such as hypertensive disorders, preterm birth, gestational diabetes, fetal growth defects (small for gestational ageand/or fetal growth restriction), placental abruption, fetal loss, and the risk that a pregnant individual in developingvascular risk factors (VR) that may lead to future vascular disease (VD): coronary heart disease, stroke, peripheralvascular disease, and heart failure. Furthermore, this document emphasises the importance of recognising APOswhen assessing VR in women. A history of APOs serves as a sufficient indicator for primary prevention of VD. In fact,adopting a healthy diet and increasing physical activity among women with APOs, starting during pregnancy and/or postpartum, and maintaining it throughout life are significant interventions that can reduce VR. On the otherhand, breastfeeding can also reduce the future VR of women, including a lower risk of mortality. Future studies evaluating the use of aspirin, statins, and metformin, among others, in women with a history of APOscould strengthen recommendations regarding pharmacotherapy for primary prevention of VD in these patients.Various healthcare system options exist to improve the transition of care for women with APOs between differenthealthcare professionals and implement long-term VR reduction strategies. One potential process could involveincorporating the fourth-trimester concept into clinical recommendations and healthcare policies.(AU)

Genetic characteristics involved in COVID-19 severity. The CARGENCORS case-control study and meta-analysis.

Pre-existing coronary artery disease (CAD), and thrombotic, inflammatory, or virus infectivity response phenomena have been associated with COVID-19 disease severity. However, the association of candidate single nucleotide variants (SNVs) related to mechanisms of COVID-19 complications has been seldom analysed. Our aim was to test and validate the effect of candidate SNVs on COVID-19 severity. CARGENCORS (CARdiovascular GENetic risk score for Risk Stratification of patients positive for SARS-CoV-2 [COVID-19] virus) is an age- and sex-matched case-control study with 818 COVID-19 cases hospitalized with hypoxemia, and 1636 controls with COVID-19 treated at home. The association between severity and SNVs related to CAD (n = 32), inflammation (n = 19), thrombosis (n = 14), virus infectivity (n = 11), and two published to be related to COVID-19 severity was tested with adjusted logistic regression models. Two external independent cohorts were used for meta-analysis (SCOURGE and UK Biobank). After adjustment for potential confounders, 14 new SNVs were associated with COVID-19 severity in the CARGENCORS Study. These SNVs were related to CAD (n = 10), thrombosis (n = 2), and inflammation (n = 2). We also confirmed eight SNVs previously related to severe COVID-19 and virus infectivity. The meta-analysis showed five SNVs associated with severe COVID-19 in adjusted analyses (rs11385942, rs1561198, rs6632704, rs6629110, and rs12329760). We identified 14 novel SNVs and confirmed eight previously related to COVID-19 severity in the CARGENCORS data. In the meta-analysis, five SNVs were significantly associated to COVID-19 severity, one of them previously related to CAD.

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.

Analysis of myocardial infarction incidence and case-fatality in the last three decades in the province of Girona.

INTRODUCTION AND OBJECTIVES: Myocardial infarction (MI) incidence and case fatality trends are highly informative but relatively untested at the population level. The objective of this work was to estimate MI incidence and case fatality in the Girona population aged 35-74 years, and to determine their 30-year trends (1990-2019). METHODS: The REGICOR (Girona Heart Registry) monitored MI incidence and case fatality rates from 1990 to 2008. For the period 2008 to 2019, we linked discharges from Girona hospitals (n=4 974 977) and mortality registry (n=70 405) during this period. Our linkage algorithm selected key MI diagnostic codes and removed duplicates. Estimates from the linkage algorithm and the REGICOR registry were compared using chi-square tests for overlapping years (2008-2009). We estimated the annual percent change (APC) of standardized MI incidence and 28-day case fatality, and analyzed their trends using joinpoint regression. RESULTS: MI incidence and case fatality estimates were similar in the linkage algorithm and the REGICOR registry. We observed significant decreasing trends in the incidence of MI. The trend was APC, -0.96% (95% confidence interval (95%CI), -1.4 to -0.53) in women from 1990 to 2019 and -4.2% (95%CI, -5.5 to -3.0) in men from 1994 to 2019. The largest decrease in case fatality was -3.8% (95%CI, -5.1 to -2.5) from 1995 to 2003 in women and -2.4% (95%CI, -2.9 to -1.9) from 1995 to 2004 in men, mainly due to prehospital case fatality declines: -1.8% (95%CI, -2.6 to -1.1) in men and -3.2% (95%CI, -4.6 to -1.8) in women. CONCLUSIONS: In Girona, MI incidence and case fatality decreased between 1990 and 2019. The incidence showed a slow but continuous decrease while case fatality only stabilized in the last decade, particularly in women.

[Documento de consenso de la Sociedad Española de Obstetricia y Ginecologia (SEGO) y el Comité Español Interdisciplinario para la Prevención Vascular (CEIPV). Ventana de oportunidad: prevención del riesgo vascular en la mujer. Resultados adversos del embarazo y riesgo de enfermedad vascular.] / Consensus document of the Spanish Society of Obstetrics and Gynecology (SEGO) and the Spanish Interdisciplinary Committee for Vascular Prevention (CEIPV). Opportunity window: vascular risk prevention in women. Adverse pregnancy outcomes and risk of vascular disease.

This document summarises the evidence regarding the association between adverse pregnancy outcomes (APOs), such as hypertensive disorders, preterm birth, gestational diabetes, fetal growth defects (small for gestational age and/or fetal growth restriction), placental abruption, fetal loss, and the risk that a pregnant individual in developing vascular risk factors (VR) that may lead to future vascular disease (VD): coronary heart disease, stroke, peripheral vascular disease, and heart failure. Furthermore, this document emphasises the importance of recognising APOs when assessing VR in women. A history of APOs serves as a sufficient indicator for primary prevention of VD. In fact, adopting a healthy diet and increasing physical activity among women with APOs, starting during pregnancy and/or postpartum, and maintaining it throughout life are significant interventions that can reduce VR. On the other hand, breastfeeding can also reduce the future VR of women, including a lower risk of mortality. Future studies evaluating the use of aspirin, statins, and metformin, among others, in women with a history of APOs could strengthen recommendations regarding pharmacotherapy for primary prevention of VD in these patients. Various healthcare system options exist to improve the transition of care for women with APOs between different healthcare professionals and implement long-term VR reduction strategies. One potential process could involve incorporating the fourth-trimester concept into clinical recommendations and healthcare policies.

Este documento resume la evidencia que existe entre los resultados adversos del embarazo (RAE), tales como son los trastornos hipertensivos, el parto pretérmino, la diabetes gestacional, los defectos en el crecimiento fetal (feto pequeño para la edad gestacional y/o restricción del crecimiento), el desprendimiento de placenta y la pérdida fetal, y el riesgo que tiene una persona gestante de desarrollar factores de riesgo vascular (RV) que pueden terminar provocando enfermedad vascular (EV) futura: cardiopatía coronaria, accidente cerebrovascular, enfermedad vascular periférica e insuficiencia cardíaca. Asimismo, este documento destaca la importancia de saber reconocer los RAE cuando se evalúa el RV en mujeres. Un antecedente de RAE es un indicador suficiente para hacer una prevención primaria de EV. De hecho, adoptar una dieta saludable y aumentar la actividad física entre las mujeres con RAE, de inicio en el embarazo y/o postparto y manteniéndolo a lo largo de la vida, son intervenciones importantes que permiten disminuir el RV. Por otro lado, la lactancia materna también puede disminuir el RV posterior de la mujer, incluyendo menos riesgo de mortalidad. Estudios futuros que evalúen el uso del ácido acetilsalicílico, las estatinas y la metformina, entre otros, en las mujeres con antecedentes de RAE podrían reforzar las recomendaciones sobre el uso de la farmacoterapia en la prevención primaria de la EV entre estas pacientes. Existen diferentes opciones dentro de los sistemas de salud para mejorar la transición de la atención de las mujeres con RAE entre los diferentes profesionales e implementar estrategias para reducir su RV a largo plazo. Una posible estrategia podría ser la incorporación del concepto del cuarto trimestre en las recomendaciones clínicas y las políticas de atención de la salud.

Predictive capacity of a genetic risk score for coronary artery disease in assessing recurrences and cardiovascular mortality among patients with myocardial infarction.

Aim: This 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. Methods: We performed a meta-analysis of individual data from three studies, namely, a prospective study including 75 patients aged <55 years, a prospective study including 184 patients with a mean age of 60.5 years, and a case-control study (77 cases and 160 controls) nested in a cohort of patients with first myocardial infarction. A GRS including 12 CAD genetic variants independent of classical cardiovascular risk factors was developed. The outcome was a composite of cardiovascular mortality and recurrent acute coronary syndrome. Results: The GRS was associated with a higher risk of recurrence [hazard ratio = 1.24; 95% confidence interval (CI): 1.04-1.47]. The inclusion of the GRS in the clinical model did not increase the model's discriminative capacity (change in C-statistic/area under the curve: 0.009; 95% CI: -0.007 to 0.025) but improved its reclassification (continuous net reclassification index: 0.29; 95% CI: 0.08-0.51). Conclusion: The GRS for CAD, independent of classical cardiovascular risk factors, was associated with a higher risk of recurrence in patients with first myocardial infarction. The predictive capacity of this GRS identified a subgroup of high-risk patients who could benefit from intensive preventive strategies.

Carotid artery stiffness and risk of vascular events and mortality: the REGICOR study.

INTRODUCTION AND OBJECTIVES: The aims of this study were to determine the dose-response association of carotid arterial stiffness with vascular outcomes and overall mortality, and to assess their added predictive capacity. METHODS: Population-based cohort study including 6468 individuals, with a median follow-up of 6.5 years. Six carotid artery stiffness indices were assessed: strain, stiffness, Peterson elasticity coefficient, compliance coefficient, distensibility coefficient, and pulse wave velocity (PWV). Incident coronary, cerebrovascular, global vascular, and total fatal events were identified. RESULTS: Carotid compliance and distensibility coefficients were not associated with any of the outcomes. Carotid stiffness, Peterson elasticity coefficient, and PWV showed a direct linear relationship to cerebrovascular disease: the risk increased by 8% (95%CI, 1-16) per stiffness unit increase, by 7% (95%CI, 2-13) per 10-unit Peterson elasticity coefficient increase, and by 26% (95%CI, 8-48) per PWV unit increase. Carotid strain showed a nonlinear association with ischemic heart disease. When strain was ≤ 0.09 units, each 0.01-unit increase was associated with a 15% lower risk of coronary events (95%CI,-33 to 6); above 0.09 units, each 0.01 increase in strain was associated with a 16% higher risk of coronary events (95%CI, 6-27). The addition of the stiffness indices did not improve the predictive capacity of validated risk functions. CONCLUSIONS: Carotid stiffness, Peterson elasticity coefficient, and PWV have a direct linear association with cerebrovascular disease risk. Carotid strain is not linearly related to U-shaped ischemic heart disease risk. The inclusion of these indexes does not improve the predictive capacity of risk functions.

Documento de consenso de la Sociedad Española de Obstetricia y Ginecologia (SEGO) y el Comité Español Interdisciplinario para la Prevención Vascular (CEIPV). Ventana de oportunidad: prevención del riesgo vascular en la mujer. Resultados adversos del embarazo y riesgo de enfermedad vascular / Consensus document of the Spanish Society of Obstetrics and Gynecology (SEGO) and the Spanish Interdisciplinary Committee for Vascular Prevention (CEIPV). Opportunity window: vascular risk prevention in women. Adverse pregnancy outcomes and risk of vascular disease

Este documento resume la evidencia que existe entre los resultados adversos del embarazo (RAE), tales como son los trastornos hipertensivos, el parto pretérmino, la diabetes gestacional, los defectos en el crecimiento fetal (feto pequeño para la edad gestacional y/o restricción del crecimiento), el desprendimiento de placenta y la pérdida fetal, y el riesgo que tiene una persona gestante de desarrollar factores de riesgo vascular (RV) que pueden terminar provocando enfermedad vascular (EV) futura: cardiopatía coronaria, accidente cerebrovascular, enfermedad vascular periférica e insuficiencia cardíaca. Asimismo, este documento destaca la importancia de saber reconocer los RAE cuando se evalúa el RV en mujeres. Un antecedente de RAE es un indicador suficiente para hacer una prevención primaria de EV. De hecho, adoptar una dieta saludable y aumentar la actividad física entre las mujeres con RAE, de inicio en el embarazo y/o postparto y manteniéndolo a lo largo de la vida, son intervenciones importantes que permiten disminuir el RV. Por otro lado, la lactancia materna también puede disminuir el RV posterior de la mujer, incluyendo menos riesgo de mortalidad. Estudios futuros que evalúen el uso del ácido acetilsalicílico, las estatinas y la metformina, entre otros, en las mujeres con antecedentes de RAE podrían reforzar las recomendaciones sobre el uso de la farmacoterapia en la prevención primaria de la EV entre estas pacientes. Existen diferentes opciones dentro de los sistemas de salud para mejorar la transición de la atención de las mujeres con RAE entre los diferentes profesionales e implementar estrategias para reducir su RV a largo plazo. Una posible estrategia podría ser la incorporación del concepto delcuarto trimestre en las recomendaciones clínicas y las políticas de atención de la salud.(AU)

This document summarises the evidence regarding the association between adverse pregnancy outcomes (APOs), such as hypertensive disorders, preterm birth, gestational diabetes, fetal growth defects (small for gestational age and/or fetal growth restriction), placental abruption, fetal loss, and the risk that a pregnant individual in developing vascular risk factors (VR) that may lead to future vascular disease (VD): coronary heart disease, stroke, peripheral vascular disease, and heart failure. Furthermore, this document emphasises the importance of recognising APOs when assessing VR in women. A history of APOs serves as a sufficient indicator for primary prevention of VD. In fact, adopting a healthy diet and increasing physical activity among women with APOs, starting during pregnancy and/or postpartum, and maintaining it throughout life are significant interventions that can reduce VR. On the other hand, breastfeeding can also reduce the future VR of women, including a lower risk of mortality.Future studies evaluating the use of aspirin, statins, and metformin, among others, in women with a history of APOs could strengthen recommendations regarding pharmacotherapy for primary prevention of VD in these patients. Various healthcare system options exist to improve the transition of care for women with APOs between different healthcare professionals and implement longterm VR reduction strategies. One potential process could involve incorporating the fourth-trimester concept into clinical recommendations and healthcare policies.(AU)

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.

Pronóstico a largo plazo de la extensión de la TAPD en una cohorte consecutiva de pacientes con IAMCEST / Long-term outcomes of extended DAPT in a real-life cohort of consecutive STEMI patients

Introducción y objetivos: La duración adecuada de la doble terapia antiagregante (DAPT) después de un infarto de miocardio con elevación del segmento ST (IAMCEST) está todavía en discusión. Métodos: Analizamos el efecto de la DAPT extendida a 5 años sobre la mortalidad global, mortalidad cardiovascular y reingreso o mortalidad cardiovascular, en una cohorte multicéntrica de pacientes con IAMCEST supervivientes al año. Resultados: Se incluyeron 3.107 pacientes hospitalizados por IAMCEST de los que el 93% recibió DAPT al alta. A los 5 años se mantenía en 275 pacientes con un perfil alto de gravedad. La mortalidad cardiovascular de los pacientes con antiagregación simple (SAPT) frente a DAPT a 5 años fue de 1,4 y 3,6% (p <0,01), respectivamente. La mortalidad no-cardiovascular fue del 3,3 frente a 5,8% (p=0,049) a 5 años, respectivamente. La incidencia del evento combinado a un año fue del 14,6% en SAPT frente a 11,8% en DAPT (p=0,496), y del 11,4 frente a 46,5% (p <0,001) a 5 años, respectivamente. El mantenimiento de la DAPT hasta los 5 años se asoció de forma independiente a mayor mortalidad: por cualquier causa (HR=2,16; IC95%, 1,40-3,33), cardiovascular (HR=2,83; IC95%, 1,37-5,84) y rehospitalización cardiovascular y mortalidad (HR=5,20; IC95%, 3,96-6,82). Un análisis emparejado por puntuación de propensión, y uno con ponderación de probabilidad inversa, confirman estos resultados. Conclusiones: Nuestros resultados sugieren la hipótesis de que, en supervivientes a un año de IAMCEST, alargar la DAPT hasta 5 años en pacientes de alto riesgo no mejora su pronóstico a largo plazo. (AU)

Introduction and objectives: Dual antiplatelet therapy (DAPT) duration after ST-segment elevation myocardial infarction (STEMI) remains a matter of debate. Methods: We analyzed the effect of DAPT on 5-year all-cause mortality, cardiovascular mortality, and cardiovascular readmission or mortality in a cohort of 1-year survivor STEMI patients. Results: A total of 3107 patients with the diagnosis of STEMI were included: 93% of them were discharged on DAPT, a therapy that persisted in 275 high-risk patients at 5 years. Cardiovascular mortality in patients on single antiplatelet therapy vs DAPT at 5 years was 1.4% vs 3.6% (P <.01), respectively, whereas noncardiovascular mortality was 3.3% vs 5.8% (P=.049) at 5 years. Cardiovascular readmission or mortality in patients with single antiplatelet therapy vs DAPT was 11.4% vs 46.5% (P <.001). Extended DAPT was independently associated with worse 5-year all-cause mortality (HR, 2.16; 95%CI, 1.40-3.33), cardiovascular mortality (HR, 2.83; 95%CI, 1.37-5.84), and cardiovascular readmission or mortality (HR, 5.20; 95%CI, 3.96-6.82). These findings were confirmed in propensity score matching and inverse probability weighting analyses. Conclusions: Our results suggest the hypothesis that, in 1-year STEMI survivors, extending DAPT up to 5 years in high-risk patients does not improve their long-term prognosis. (AU)

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

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). (AU)

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 diseases 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 cardiovascular diseases risk, lifetime cardiovascular diseases 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 diseases events (myocardial infarction, stroke and vascular mortality) 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). (AU)

Asociación entre metilación del ADN y tabaquismo en pacientes con isquemia crónica amenazante de extremidades inferiores / Association between DNA methylation and smoking in patients with chronic limb-threatening ischemia

Introducción y objetivo: estudiar la asociación entre tabaquismo y el nivel de metilación de dos regiones genómicas en pacientes con enfermedad arterial periférica (EAP). Método: estudio transversal de 297 pacientes (edad media: 69,6 años; varones: 78,5 %) diagnosticados de isquemia crónica de extremidades inferiores en diferentes estadios clínicos entre marzo de 2016 y diciembre de 2019en el servicio de cirugía vascular del Hospital del mar (Barcelona). Se analizó la metilación de Cg02156642 y deCg03636183 asociados en otros estudios al tabaquismo. Se realizó una regresión lineal múltiple para discriminar lasvariables asociadas al nivel de metilación. Se calculó el área bajo la curva ROC para discriminar el nivel de metilaciónentre fumadores y no fumadores. Resultados: de la muestra, 46 pacientes (15,5 %) eran no fumadores; 132 (44,4 %), exfumadores y 119 (40,1 %),fumadores. No se observó una asociación entre la exposición al tabaco y el nivel de metilación del Cg02156642,pero sí con el de Cg03636183: los fumadores presentaban menor nivel de metilación y, además, a más carga detabaco menos metilación (Rho de Spearman: -0,324; p < 0,001).Un nivel de metilación en este CpG del 80 % tiene una sensibilidad (S) del 90,0 % y una especificidad (E) del83,5 % para discriminar entre fumadores y nunca fumadores. Para discriminar entre fumadores y exfumadores,un nivel de metilación del 75 % tiene una S del 69 % y una E del 56,9 %.Al ajustar por todas las variables relacionadas con la metilación, la magnitud de esta asociación entre Cg03636183y tabaquismo se mantenía signifi cativa entre los nunca fumadores y los fumadores. Conclusiones: la metilación del cpg cg03636183 se asocia a tabaquismo en pacientes con eap y está directamenterelacionada con la carga de tabaco. Este biomarcador podría utilizarse en la práctica clínica para valorar el consumode tabaco de nuestros pacientes.(AU)

Introduction and objective: to study the association between smoking and the methylation level of 2 genomicregions in patients with peripheral artery disease (PAD). Method: cross-sectional study of 297 patients (mean age, 69.6 years; males, 78.5%) diagnosed with chronic lowerextremity ischemia at various clinical stages from march 2016 through December 2019 at the Vascular Surgery Unitof Hospital del mar, Barcelona, Catalonia, Spain. methylation analysis of Cg02156642 and Cg03636183, previouslyassociated with smoking in former studies was performed. multiple linear regression was conducted to identifyvariables associated with methylation levels. The area under the ROC curve was estimated to discriminate meth-ylation levels between smokers and non-smokers. Results: among the sample, 46 patients (15.5%) were non-smokers, 132 (44.4%) were former smokers, and 119(40.1%) were current smokers. No association was seen between tobacco exposure and methylation levels ofCg02156642. However, an association was found with Cg03636183: smokers had lower methylation levels, anda higher smoking load was associated with lower methylation (Spearman's Rho, -0.324; p < .001). A methylationlevel of 80% in this region showed a 90.0% sensitivity and an 83.5% specificity to discriminate between smokersand never smokers. To discriminate between smokers and former smokers, a methylation level of 75% had an 69%sensitivity and an 56.9% specificity. After adjusting for all variables associated with methylation, the associationbetween Cg03636183 and smoking remained significant among never smokers and smokers. Conclusions: methylation of the Cg03636183 region is associated with smoking in patients with PAD and is directlyassociated with the smoking load. This biomarker could be used in the routine clinical practice to assess tobaccouse in our patients.(AU)

Asociación de la actividad física con la funcionalidad de las lipoproteínas de alta densidad en una cohorte de base poblacional: el estudio REGICOR / Association of physical activity with high-density lipoprotein functionality in a population-based cohort: the REGICOR study

Introducción y objetivos Determinar la relación dosis-respuesta entre la actividad física en el tiempo libre (AFTL) actual y pasada, total y según su intensidad, y la funcionalidad de las lipoproteínas de alta densidad (HDL). Métodos Se seleccionó a 642 participantes de un estudio poblacional: la edad media era de 63,2 años y el 51,1% eran mujeres. Se incluyeron datos de la visita inicial y de un seguimiento a 4 años. La AFTL se evaluó mediante cuestionarios validados. Se determinó la capacidad de eflujo de colesterol y antioxidante en el seguimiento. Se utilizaron modelos de regresión lineal y aditivos para evaluar la relación dosis-respuesta. Resultados Se observó una relación inversa y lineal entre la AFTL total actual (entre 0-400 MET x min/día) y la capacidad antioxidante de HDL (coeficiente de regresión [beta]: -0,022; IC95%, -0,030; -0,013), con una meseta por encima de este umbral. Se observaron resultados similares para la AFTL de intensidad moderada (beta: -0,028; IC95%, -0,049; -0,007) y vigorosa (beta: -0,025; IC95%, -0,043; -0,007), pero no para AFTL de intensidad ligera. La AFTL en el seguimiento no se asoció con la capacidad de eflujo de colesterol. La AFTL basal no se asoció con la funcionalidad de HDL. Conclusiones La AFTL de intensidad moderada-vigorosa actual se asocia de forma no lineal con una mayor capacidad antioxidante de las partículas de HDL. Se observa un beneficio máximo con dosis intermedias-bajas de AFTL (0-400 MET x min/día). Nuestros resultados concuerdan con las recomendaciones de práctica de AFTL y sugieren una asociación con la funcionalidad de HDL (AU)

Introduction and objectives To determine the dose-response association between current and past leisure-time physical activity (LTPA), total and at different intensities, and high-density lipoprotein (HDL) functionality parameters. Methods Study participants (n=642) were randomly drawn from a large population-based survey. Mean age of the participants was 63.2 years and 51.1% were women. The analysis included data from a baseline and a follow-up visit (median follow-up, 4 years). LTPA was assessed using validated questionnaires at both visits. Two main HDL functions were assessed: cholesterol efflux capacity and HDL antioxidant capacity, at the follow-up visit. Linear regression and linear additive models were used to assess the linear and nonlinear association between LTPA and HDL functionality. Results Total LTPA at follow-up showed an inverse and linear relationship between 0 and 400 METs x min/d with HDL antioxidant capacity (regression coefficient [beta]: −0.022; 95%CI, −0.030, −0.013), with a plateau above this threshold. The results were similar for moderate (beta: −0.028; 95%CI, −0.049, −0.007) and vigorous (beta: −0.025; 95%CI, −0.043, −0.007), but not for light-intensity LTPA. LTPA at follow-up was not associated with cholesterol efflux capacity. Baseline LTPA was not associated with any of the HDL functionality parameters analyzed. Conclusions Current moderate and vigorous LTPA showed a nonlinear association with higher HDL antioxidant capacity. Maximal benefit was observed with low-intermediate doses of total LTPA (up to 400 METs x min/d). Our results agree with current recommendations for moderate-vigorous LTPA practice and suggest an association between PA and HDL functionality in the general population (AU)

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.

The "Bayés Spirit" as a guide for new generations: How to combine one's personal life and friendships with science and profession.

Recent studies suggest that up to a quarter of physicians in training suffer from burnout and psychological disorders. Scientist-physicians, cardiologists, cardiology residents, and first-year medical residents seem to be more prone to developing varying degrees of emotional distress. Concerned about the new generations of clinicians and researchers, the authors aim to provide guidelines for reconciling professional success with a fulfilling and satisfying personal life. The figure of Antonio Bayés de Luna (cardiology and electrocardiology guru) is used as the ideal example to learn how to combine one's personal life, family, and friendships with science and their professional career. This can be done in a healthy and balanced way, prioritizing the former while continuing to have an intense dedication to the latter.