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Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2022-2023. Tutor/Director: Carmona Flores, Manuel, Soudah Prieto, Eduardo, The aortic dissection is a cardiovascular disease that results from the rupture of the inner layer of the aorta. Type B aortic dissections commonly become a chronic disease with a high long-term morbidity and mortality rates. Current treatments include open surgery repair and thoracic endovascular aortic repair (TEVAR). However, new non-invasive treatments are being developed that favour the own regeneration of the tissue, avoiding the permanent presence of a foreign device in the body. This project focuses on the understanding of a new treatment with a medical device, an aortic patch, by in silico testing. The goal is to determine the performance of the patch in a simulated aortic dissection and then compare it with the current treatment with the stent graft (TEVAR), to determine if it would avoid the hypertension that can be caused by the stent. To do the first part, it was created a model of the aortic dissection, but due to complications with the simulation, this part of the project couldn’t be finished, and the performance of the patch in the aortic dissection couldn’t be determined. To do the second part three models were created: healthy aorta, aortic dissection with stent graft and aortic dissection with patch. A transient simulation was run for the three models and the pressure waveform was analyzed. The results show that the pressure in the stent graft model is higher, and the patch has a similar response to the healthy aorta. However, all the models presented hypertension (including the healthy aorta) and the differences between the models are too small to be concluding, so it cannot be assured that the patch is a better option than the stent graft to avoid causing hypertension in the aortic dissection treatment.

Ischemic heart disease (IHD) is the leading global cause of death and is assumed to entail a significant social and economic burden globally. This study aimed to evaluate incidence and mortality trends of IHD in Spain and to estimate direct medical costs.Admission files corresponding to patients with IHD registered between 2011 and 2019 were obtained from a Spanish hospital discharge database and analyzed in a retrospective study.Admission data corresponding to 814,740 patients with IHD was analyzed. The majority of patients were males, and about half of the hospitalizations were due to an acute myocardial infarction. Incidence decreased significantly in most age groups over time, while hospital mortality rate remained stable (4.4%). Additionally, mortality rate was significantly higher among females (6.6%). Median admission cost was €5175; the higher costs per admission were found in patients with an acute myocardial infarction and in admissions with an ICU stay. The annual cost of hospital care was €693.8 million.Despite the decreasing trends described in the general population, hospital mortality rate was constant among hospitalized patients during the study period. The higher hospital mortality rate described among females should be considered in further studies and protocol revisions.

Introducción Los pacientes, tras un ictus o un ataque isquémico transitorio, presentan un riesgo muy elevado de sufrir nuevos episodios vasculares. La reducción del nivel de colesterol unido a lipoproteínas de baja densidad (cLDL) reduce la incidencia de nuevos episodios, si bien una proporción importante de pacientes no alcanza los objetivos terapéuticos recomendados con los tratamientos hipolipemiantes actuales. El objetivo de este documento de consenso es actualizar el papel de los inhibidores de la proproteína convertasa subtilisina/kexina tipo 9 (iPCSK9; alirocumab y evolocumab) en la prevención secundaria de episodios vasculares en pacientes con ictus isquémico previo. Métodos Se realizó una revisión bibliográfica para identificar las principales evidencias sobre el uso de iPCSK9 en estos pacientes y los objetivos terapéuticos recomendados de cLDL. Los resultados se discutieron en 2 reuniones de consenso, que constituyeron la base para la elaboración del documento. Conclusiones Los iPSCSK9 son eficaces en la reducción del riesgo vascular en prevención secundaria y, específicamente, evolocumab ha demostrado esta reducción en pacientes con ictus isquémico previo. Ambos fármacos han demostrado un buen perfil de seguridad, incluso en pacientes que alcanzaron un nivel de cLDL < 20 mg/dL. En este sentido, en el subestudio de episodios neurocognitivos con evolocumab no se observó ninguna señal de empeoramiento de la función cognitiva en pacientes con nivel muy bajo de cLDL. Con base en estas evidencias, en el documento se presentan recomendaciones prácticas sobre el uso de iPCSK9 para la prevención secundaria y seguimiento de episodios vasculares en pacientes con ictus isquémico previo. Introduction Patients with history of stroke or transient ischaemic attack present considerable risk of future vascular events. Reducing levels of low-density lipoprotein (LDL) cholesterol decreases the incidence of new vascular events, although in a substantial number of patients, the currently available lipid-lowering therapies fail to achieve the therapeutic goals recommended in clinical guidelines. The aim of this consensus statement is to provide updated information on the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab in the secondary prevention of vascular events in patients with history of ischaemic stroke. Methods A literature review was performed to identify the main evidence on the use of PCSK9 inhibitors in these patients and the recommended therapeutic targets of LDL cholesterol. The results were discussed in 2 consensus meetings that constituted the basis for the drafting of the document. Conclusions PCSK9 inhibitors are effective in reducing vascular risk in secondary prevention; evolocumab specifically has achieved this reduction in patients with history of ischaemic stroke. Moreover, both alirocumab and evolocumab present good safety profiles, even in patients achieving LDL cholesterol levels < 20 mg/dL, and no signs of cognitive impairment have been observed in patients treated with evolocumab who achieved very low levels of LDL cholesterol. In the light of this evidence, we provide practical recommendations about the use of PCSK9 inhibitors in secondary prevention of vascular events in patients with history of ischaemic stroke and follow-up of these patients.

Atherosclerosis is a chronic inflammatory and degenerative process that mainly occurs in large- and medium-sized arteries and is morphologically characterized by asymmetric focal thickenings of the innermost layer of the artery, the intima. This process is the basis of cardiovascular diseases (CVDs), the most common cause of death worldwide. Some studies suggest a bidirectional link between atherosclerosis and the consequent CVD with COVID-19. The aims of this narrative review are (1) to provide an overview of the most recent studies that point out a bidirectional relation between COVID-19 and atherosclerosis and (2) to summarize the impact of cardiovascular drugs on COVID-19 outcomes. A growing body of evidence shows that COVID-19 prognosis in individuals with CVD is worse compared with those without. Moreover, various studies have reported the emergence of newly diagnosed patients with CVD after COVID-19. The most common treatments for CVD may influence COVID-19 outcomes. Thus, their implication in the infection process is briefly discussed in this review. A better understanding of the link among atherosclerosis, CVD, and COVID-19 could proactively identify risk factors and, as a result, develop strategies to improve the prognosis for these patients.

Heart failure (HF) is classified according to the degree of reduction in left ventricular ejection fraction (EF) in HF with reduced, mildly reduced, and preserved EF. Biomarkers could behave differently depending on EF type. Here, we analyze the soluble form of the AXL receptor tyrosine kinase (sAXL) in HF patients with reduced and preserved EF. Two groups of HF patients with reduced (HFrEF; n = 134) and preserved ejection fraction (HFpEF; n = 134) were included in this prospective observational study, with measurements of candidate biomarkers and functional, clinical, and echocardiographic variables. A Cox regression model was used to determine predictors for clinical events: cardiovascular mortality and all-cause mortality. sAXL circulating values predicted outcome in HF: for a 1.0 ng/mL increase in serum sAXL, the mortality hazard ratio (HR) was 1.019 for HFrEF (95% CI 1.000 to 1.038) and 1.032 for HFpEF (95% CI 1.013 to 1.052). In a multivariable Cox regression analysis, sAXL and NT-proBNP were independent markers for all-cause and cardiovascular mortality in HFpEF. In contrast, only NT-proBNP remained significant in the HFrEF group. When analyzing the event-free survival at a mean follow-up of 3.6 years, HFrEF and HFpEF patients in the higher quartile of sAXL had a reduced survival time. Interestingly, sAXL is a reliable predictor for all-cause and cardiovascular mortality only in the HFpEF cohort. The results suggest an important role for AXL in HFpEF, supporting sAXL evaluation in larger clinical studies and pointing to AXL as a potential target for HF therapy.

Williams-Beuren syndrome (WBS) is a rare disorder caused by a recurrent microdeletion with hallmarks of cardiovascular manifestations, mainly supra-valvular aortic stenosis (SVAS). Unfortunately, there is currently no efficient treatment. We investigated the effect of chronic oral treatment with curcumin and verapamil on the cardiovascular phenotype of a murine model of WBS harbouring a similar deletion, CD (complete deletion) mice. We analysed systolic blood pressure in vivo and the histopathology of the ascending aorta and the left ventricular myocardium to determine the effects of treatments and their underlying mechanism. Molecular analysis showed significantly upregulated xanthine oxidoreductase (XOR) expression in the aorta and left ventricular myocardium of CD mice. This overexpression is concomitant with increased levels of nitrated proteins as a result of byproduct-mediated oxidative stress damage, indicating that XOR-generated oxidative stress impacts the pathophysiology of cardiovascular manifestations in WBS. Only the combined therapy of curcumin and verapamil resulted in a significant improvement of cardiovascular parameters via activation of the nuclear factor erythroid 2 (NRF2) and reduction of XOR and nitrated protein levels. Our data suggested that the inhibition of XOR and oxidative stress damage could help prevent the severe cardiovascular injuries of this disorder. This research was funded by Ministerio de Ciencia e Innovación (AEI/MINEICO/FEDER, UE), grant number: SAF2016-78508-R to V.C. and PID2020-113634RB-C2 to G.E.; from Association “Autour des Williams” to V.C.; and Generalitat de Catalunya (2017-SGR1794) to L.A.P.J.

RESUMEN La hipertensión arterial es el factor de riesgo cardiovascular más prevalente. A pesar del tratamiento farmacológico, un alto porcentaje de pacientes no consiguen un adecuado control. La denervación renal es una intervención mínimamente invasiva para el tratamiento de la hipertensión que implica la interrupción de los nervios simpáticos renales mediante un abordaje con catéter. Los estudios iniciales mostraron resultados prometedores, pero los controvertidos resultados del ensayo SYMPLICITY HTN-3 llevaron al abandono de la técnica. En los últimos 3 años han aparecido los resultados de nuevos ensayos clínicos, con nuevos dispositivos y en diferentes poblaciones, que demuestran definitivamente la eficacia de la denervación renal. En este documento de posicionamiento conjunto de la Sociedad Española de Hipertensión-Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA) y la Asociación de Cardiología Intervencionista de la Sociedad Española de Cardiología (ACI-SEC) se revisa la evidencia disponible sobre la eficacia y la seguridad de la denervación renal en el tratamiento de la hipertensión. A partir de los resultados de los ensayos clínicos, se generan recomendaciones sobre qué pacientes y en qué condiciones podrían ser candidatos a una denervación renal.

Treballs Finals de Grau de Nutrició Humana i Dietètica, Facultat de Farmàcia i Ciències de l'Alimentació, Campus de l'Alimentació de Torribera, Universitat de Barcelona. Curs: 2022-2023. Tutor: Maria Grau Magaña, [cat] L’adhesió a un patró alimentari saludable i sostenible, com la Dieta Mediterrània, forma part del tractament de persones que han sofert un esdeveniment cardiovascular. Pot ajudar a la seva prompta recuperació a més de a prevenir l’aparició d’un altre episodi advers. Els objectius d’aquest treball són: (1) adaptar un protocol d’educació nutricional destinat a pacients supervivents d’un episodi cardiovascular isquèmic; (2) avaluar la usabilitat i factibilitat d’aquest programa. S’ha adaptat un protocol d’una intervenció d’educació nutricional per promoure hàbits dietètics saludables dissenyat prèviament per la Xarxa Fit4foodBcn. A continuació, s’ha realitzat aquesta intervenció a 3 pacients ingressats per infart agut de miocardi en un hospital de tercer nivell. S’han avaluat els materials utilitzats, la informació transmesa i el desenvolupament de les diferents sessions del programa a través de qüestionaris i entrevistes. D’aquestes s’extreuen suggeriments de millora i també observacions dels educadors durant les sessions. L’hospital com a emplaçament de la intervenció comporta dificultats, tal com l’estat d’ànim i de salut del pacient al moment de realitzar les sessions, però alhora és un facilitador, degut a que el pacient no s’ha de desplaçar i té temps disponible per realitzar les sessions. Els participants manifesten un nivell alt de satisfacció amb la intervenció, així com una adequada comprensibilitat i utilitat de la informació i els materials, pel qual la intervenció resulta factible de realitzar en aquest hospital., [eng] Adherence to a healthy and sustainable dietary pattern, such as the Mediterranean Diet, is part of the treatment for people who have suffered a cardiovascular event. It can faster their recovery and prevent the appearance of another adverse episode. The aims of this project are: (1) adapt a nutritional education protocol intended for patients who have survived an ischemic cardiovascular episode; (2) evaluate the usability and feasibility of this program. It has been adapted a protocol of a nutritional education intervention to promote healthy dietary habits previously designed by the Fit4foodBcn Network. Then, this intervention was performed on 3 inpatients admitted for myocardial infarction in a third-level hospital. The materials used, the information transmitted, and the development of the different sessions of the program have been evaluated through questionnaires and interviews. Suggestions for improvement including observations of the educators during the sessions are extracted. The hospital as the place of the intervention entails difficulties, such as the patient’s state of mind and health at the time of the sessions but is also a facilitator since the patient does not have to travel and has time available to carry out the sessions. The participants express a high level of satisfaction with the intervention, just as well as adequate comprehensibility and usefulness to the information and materials, which makes the program feasible to perform in this hospital.

Background The long-term cardiovascular (CV) outcomes of COVID-19 have not been fully explored. Methods This was an international, multicenter, retrospective cohort study conducted between February and December 2020. Consecutive patients ≥18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 were included. Patients were classified into two cohorts depending on the nasopharyngeal swab result and clinical status: confirmed COVID-19 (positive RT-PCR) and control (without suggestive symptoms and negative RT-PCR). Data were obtained from electronic records, and clinical follow-up was performed at 1-year. The primary outcome was CV death at 1-year. Secondary outcomes included arterial thrombotic events (ATE), venous thromboembolism (VTE), and serious cardiac arrhythmias. An independent clinical event committee adjudicated events. A Cox proportional hazards model adjusted for all baseline characteristics was used for comparing outcomes between groups. A prespecified landmark analysis was performed to assess events during the post-acute phase (31–365 days). Results A total of 4,427 patients were included: 3,578 (80.8%) in the COVID-19 and 849 (19.2%) control cohorts. At one year, there were no significant differences in the primary endpoint of CV death between the COVID-19 and control cohorts (1.4% vs. 0.8%; HRadj 1.28 [0.56–2.91]; p = 0.555), but there was a higher risk of all-cause death (17.8% vs. 4.0%; HRadj 2.82 [1.99–4.0]; p = 0.001). COVID-19 cohort had higher rates of ATE (2.5% vs. 0.8%, HRadj 2.26 [1.02–4.99]; p = 0.044), VTE (3.7% vs. 0.4%, HRadj 9.33 [2.93–29.70]; p = 0.001), and serious cardiac arrhythmias (2.5% vs. 0.6%, HRadj 3.37 [1.35–8.46]; p = 0.010). During the post-acute phase, there were no significant differences in CV death (0.6% vs. 0.7%; HRadj 0.67 [0.25–1.80]; p = 0.425), but there was a higher risk of deep vein thrombosis (0.6% vs. 0.0%; p = 0.028). Re-hospitalization rate was lower in the COVID-19 cohort compared to the control cohort (13.9% vs. 20.6%; p = 0.001). Conclusions At 1-year, patients with COVID-19 experienced an increased risk of all-cause death and adverse CV events, including ATE, VTE, and serious cardiac arrhythmias, but not CV death. Study registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT04359927.

[spa] Las enfermedades cardiovasculares (ECV), representan la principal causa de morbimortalidad en los países desarrollados y su aumento continúa a nivel mundial. Su denominación hace referencia a varias enfermedades de diferentes etiologías, cuya causa más común es la aterosclerosis. Sabemos que la adherencia a un estilo de vida poco saludable junto a unos malos hábitos alimentarios se traduce en un aumento del riesgo cardiovascular (RCV). Sin embargo, diversos estudios como el estudio PREDIMED han mostrado que seguir una dieta saludable como la Dieta Mediterránea (DietMed) y la práctica de actividad física (AF) de manera regular, podrían limitar o reducir la aparición de ECV y posiblemente con un menor uso de medicamentos para las ECV. La DietMed se caracteriza por una ingesta notable de aceite de oliva virgen extra, frutos secos, verduras, legumbres y cereales integrales, un consumo moderado de pescado, marisco y carne blanca, un bajo consumo de productos lácteos, carnes rojas y procesadas y la ingesta ocasional de alcohol en forma de vino en las principales comidas. Por otra parte, la AF regular se asocia con menores tasas de mortalidad cardiovascular y la mortalidad total. Varios factores de riesgo (FR) pueden ser modificados de forma efectiva mediante la práctica regular de ejercicio. Además, de medidas preventivas resulta fundamental la implantación de un tratamiento farmacológico. El objetivo de esta tesis doctoral es determinar si seguir una DietMed (en relación a una dieta control baja en grasas), incrementar la calidad de un patrón dietético o promover el consumo de alguno de sus alimentos principales (aceite de oliva, frutos secos, verduras, frutas, legumbres, cereales integrales, pescado, carnes blancas, lácteos fermentados) se asocia con un menor debut de individuos que deban iniciar un tratamiento nuevo de fármacos para el tratamiento de la diabetes, dislipemia, hipertensión, así como para evitar la aparición de trombos en una población de adultos mayores con alto riesgo cardiovascular en el marco del estudio PREDIMED. Adicionalmente, se pretende evaluar si la alta adherencia a la DietMed y la actividad física en tiempo libre (LTPA, por sus siglas en inglés) de forma individual y combinada, están asociadas con un menor riesgo de iniciar el uso de fármacos cardiometabólicos. Los resultados mostraron que una DietMed enriquecida con aceite de oliva virgen extra (AOVE) es capaz de disminuir el riesgo de iniciar el uso de inhibidores de la epóxido reductasa de vitamina K (ERK) respecto a la dieta control. El uso de ERK parece asociarse con un mayor riesgo de ECV en los participantes del grupo control. Por otra parte, se observó que una DietMed+AOVE es capaz de reducir el riesgo de iniciar el uso de medicamentos antihipertensivos en comparación con los participantes del grupo control un 14%. Además, se observó que en este mismo grupo hubo una disminución de intensificar la terapia antihipertensiva en los participantes que usaban dos fármacos al inicio del estudio. Finalmente, una alta adherencia a una DietMed junto con altos niveles de AF tuvieron un efecto sinérgico para reducir las concentraciones de glucosa y el uso de fármacos cardiovasculares. En conclusión, nuestro trabajo confirma los hallazgos previos y contribuye a la evidencia que seguir una DietMed mejora los FRCV y sugieren que este patrón dietético va asociado a una reducción en el riesgo de empezar a ser usuario de medicación para las ECV, reforzando la idea de que la DietMed es un patrón útil en la prevención de la enfermedad cardiometabólica en personas mayores con alto RCV. Además, en las personas con alto RCV, la adherencia a la DietMed en combinación con LTPA se asocia a una disminución del riesgo de iniciar medicamentos relacionados con ECV., [eng] INTRODUCTION: Cardiovascular diseases (CVD) represent the main cause of morbidity and mortality in developed countries and their cause is atherosclerosis. An unhealthy lifestyle together with poor eating habits increases cardiovascular risk (CVR). The PREDIMED study has shown that following a Mediterranean Diet (MedDiet) and practicing physical activity (PA) on a regular basis could reduce the appearance of CVD by 30%. The MedDiet is characterized by an intake of olive oil, nuts, vegetables, fruits, legumes, whole grains, fish, white meat, fermented dairy products. Also, regular PA is associated with lower rates of cardiovascular, as well as improvement of some risk factors. In addition to these preventive measures, the implementation of pharmacological treatment is essential. OBJECTIVES: The objective of this doctoral thesis is to determine wheter to follow a MedDiet (in relation to a low-fat control diet), increase the quality of a dietary pattern or promote the consumption of key foods in the MedDiet is associated with a lower debut of starting a new cardiometabolic treatment. In addition, it is intended to assess whether high adherence to the MedDiet and leisure-time physical activity (LTPA) individually or in combination, are associated with a lower risk of starting the use of these drugs. The results showed that a MedDiet enriched with extra virgin olive oil (EVOO) reduces the risk of starting the use of antithrombotic and antihypertensive compared to the control diet, reduces the risk of starting the use of antihypertensive drugs. RESULTS: The results showed that a MedDiet enriched with extra virgin olive oil (EVOO) reduces the risk of starting the use of antithrombotic and antihypertensive drugs. In addition, it was observed a decreased intensifying antihypertensive therapy in participants that used two drugs at baseline. Finally, high adherence to the MedDiet and regular PA had a synergistic effect on the reduction of glucose concentrations and the use of cardiovascular drugs. CONCLUSION: In conclusion, our work contributes to the evidence that following a MedDiet improves CVRF and suggests that this dietary pattern is associated with a reduced risk of starting to use CVD medication. Furthermore, in people with high CVR, adherence to the MedDiet in combination with LTPA is associated with a lower risk of starting a new CVD treatment.

[spa] Estudios recientes sugieren la existencia de una afectación miocárdica propia en el síndrome de Marfan (SM). Cabe mencionar que no hay datos sobre el potencial impacto diferencial del género en la manifestación de los signos de la miocardiopatía en SM, ni evidencia para apoyar el hecho de que el deporte con una carga mayor que baja siempre se haya desaconsejado en pacientes con el SM. Los objetivos son determinar si existe una respuesta funcional miocárdica anormal en el SM mediante la detección de la deformación miocárdica alterada y si ésta presenta patrones de deformación regional alterados típicos de los estados de incremento de postcarga. Evaluar el impacto del ejercicio físico en la dilatación de aorta ascendente y la miocardiopatía en el SM. Examinar diferencias de género en la presentación de dicha deformación alterada y los factores asociados a la misma. En el primer proyecto se han estudiado tres poblaciones: ratones de 4 y 9 meses de edad y pacientes humanos, con la medición de la presión arterial y la ecocardiografía avanzada con el Modo 2D, M y Doppler Tisular. El principal hallazgo fue la alta prevalencia de engrosamiento postsistólico (EPS) en el SM, detectado tanto en un modelo experimental murino como en una cohorte de pacientes con SM. En los ratones de 4 meses de edad, la presencia de EPS se asoció a la dilatación de la raíz aórtica a pesar de que no hubo diferencias estadísticamente significativas en la presión arterial entre el grupo de ratones con EPS y aquellos sin EPS. Curiosamente, los pacientes con EPS muestran una presión arterial sistólica más baja que los controles y se observa una asociación entre el aumento de la prevalencia de EPS y la dilatación aórtica en pacientes muy jóvenes. En el segundo proyecto se han analizado los ratones de 4 meses antes y después de la intervención en forma del programa del entreno físico controlado a moderada carga durante 5 meses. Los resultados evidencian que el ejercicio regular de intensidad moderada no acelera la tasa de dilatación aórtica, sino que más bien normaliza su progresión a valores comparables al observado en los animales sanos. Los ratones con SM del grupo entrenado mostraron un ligero aumento de la presión arterial sistólica, en comparación con los ratones sin SM. Sin embargo, vimos que, a pesar de este incremento en la presión arterial, hubo una menor dilatación aórtica y una menor hipertrofia de ventrículo izquierdo. En el tercer proyecto se han correlacionado los datos clínico-farmacológicos con los datos ecocardiográficos de los pacientes humanos según el sexo, revelando un claro impacto diferencial del género, siendo significativamente más frecuente el EPS en las mujeres, hecho asociado a que las mujeres reciben con menor frecuencia tratamiento con betabloqueadores y losartan, a pesar de que los diámetros aórticos y ventriculares son muy similares entre ambos géneros. Cabe destacar que la presión arterial es más alta en el caso de mujeres con EPS presente, en comparación con las que no presentan este signo. La alta prevalencia del EPS, tanto en ratones como en pacientes con SM, sugiere la existencia de miocardiopatía por sobrecarga de presión. Este marcador puede proporcionar una herramienta de detección y monitorización del remodelado cardíaco. En un modelo murino de SM, el ejercicio dinámico de intensidad moderada se asocia a una menor dilatación aórtica, menor hipertrofia cardíaca y menor frecuencia de EPS. La presencia de EPS se observa con mayor frecuencia en pacientes mujeres con SM que en pacientes de sexo masculino; sin embargo, las mujeres con SM reciben con menor frecuencia tratamiento vasodilatador a pesar de que su presión es significativamente más alta., [eng] Several studies have observed myocardial abnormalities in Marfan syndrome (MS). There are no data on the potential differential impact of gender on manifestation of the signs of cardiomyopathy in MS and the evidence is lacking to support the fact that sport with a load greater than low has always been discouraged in those patients. We postulate that patients with MS may have the ventricular myocardium more susceptible to afterload and therefore may develop greater segmental left ventricular (LV) wall stress heterogeneity due to underlying abnormal tissue of the arterial wall and/or myocardium. In the first project, three populations have been studied, 4- and 9-month-old mice and human patients. Main finding was the high prevalence of postsystolic thickening (PST) in MS and its association with aortic root dilatation, both in the experimental murine model and in a cohort of young patients. In the second project, the population of 4 month-old mice before and after the controlled physical training program at moderate load during 5 months have been analyzed. Regular exercise of moderate intensity does not accelerate the rate of aortic dilatation, but rather normalizes its progression. The third project reveals a clear differential impact of gender, the PST is significantly more frequent in women. This finding is associated with the fact that women receive treatment with beta-blockers and losartan less frequently, despite the fact that aortic and ventricular diameters are very similar between both genders. The high prevalence of the PST, both in mice and in patients with MS, suggests the finding of pressure overload cardiomyopathy. The PST can provide a tool for detection and monitoring of cardiac remodeling and support the decision to start preventive therapies in patients with MS, even with normal blood pressure levels. In a murine model of MS, moderate-intensity dynamic exercise is associated with less aortic dilation, less cardiac hypertrophy, and lower PST prevalence. The presence of PST is observed more frequently in female patients with MS than in male patients; however, women with MS receive vasodilator treatment less frequently despite the fact that their pressure is significantly higher.

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

[spa] El envejecimiento de la población y la propia morbididad cardiovascular provocará que incremente la demanda asistencial de unidades de rehabilitación cardiorrespiratoria en el sistema sanitario público en las siguientes décadas. El índice de participación en programas de rehabilitación cardíaca Fase II en España está muy por debajo de la mayoría de países europeos. Además, el alto abandono de la práctica regular de ejercicio físico y de los hábitos saludables tras finalizar dicha fase supervisada y dirigida ambulatoria dificulta el control de los factores de riesgo cardiovascular, lo cuál aumenta el porcentaje de recidiva del evento coronario durante la Fase III de mantenimiento. El tratamiento interdisciplinario tras síndrome coronario agudo provoca una aumento de la supervivencia, mejora del pronóstico y reducción de los costes sanitarios futuros. El entrenamiento de la resistencia aeróbica continuo variable de alta intensidad que contempla fases de recuperación activa entre los períodos de carga objetivo es el método que ha objetivado mayores mejoras en la capacidad funcional, composición corporal, pautas alimentarias mediterráneas y nivel de adherencia a la actividad física. La combinación con la tonificación muscular dinámica con sobrecarga ha demostrado ser un entrenamiento complementario y seguro. Sin embargo existen importantes diferencias en la terminología e intensidades óptimas para el tratamiento del síndrome coronario agudo en lo que refiere al entrenamiento de la resistencia aeróbica, sobretodo en aquellos trabajos publicados en español. A pesar de que son múltiples los estudios que demuestran que los períodos de recuperación entre las cargas objetivo deben ser activos, son muchos los artículos también que definen a esta metodología de entrenamiento como interválico (traducción literal del inglés interval), que per se contemplaría descanso pasivo, cuando en realidad se trata de un método continuo variable. Frente al auge de la terminología HIIT (High Intensity Interval Training) subyace la necesidad de proponer consenso a la terminología e intensidades óptimas del entrenamiento de la resistencia aeróbica. Por otro lado, cabe añadir que son escasos los estudios desarrollados en la Fase III de mantenimiento de la rehabilitación cardíaca. La aplicación de esta metodología de entrenamiento combinada a nivel comunitario y seguimiento mediante telemedicina nos ha mostrado mejoras significativas a largo plazo en la capacidad funcional además de beneficios a nivel de adherencia a la actividad física autónoma. Sin embargo, hemos documentado también la dificultad del mantenimiento de los beneficios en la composición corporal y pautas nutricionales conseguidos después de la rehabilitación cardíaca Fase II ambulatoria durante la Fase III autónoma. Los resultados evidencian la necesidad de estructurar programas extra-hospitalarios interdisciplinarios que involucren a la medicina primaria y a las instituciones públicas con el objetivo de garantizar una mayor participación y adherencia. Finalmente, la prescripción de ejercicio físico específico para la musculatura respiratoria continúa siendo una disciplina prácticamente reservada para la enfermedad pulmonar obstructiva crónica. El entrenamiento de la musculatura inspiratoria cuenta con escasa relevancia en programas de rehabilitación cardíaca. La aplicación de este entrenamiento específico durante la Fase II ambulatoria en un grupo aleatorizado de pacientes que también realizaban el programa convencional nos permitió observar incrementos significativos en la capacidad funcional.

Treballs Finals de Grau d'Enginyeria Informàtica, Facultat de Matemàtiques, Universitat de Barcelona, Any: 2022, Director: Sergio Escalera Guerrero, Carles Casacuberta i Rubén Ballester Bautista, [en] Cardiovascular diseases are a major cause of death and disability. Deep learning-based segmentation methods could help to reduce their severity by aiding in early diagnosing but high levels of accuracy are necessary. The vast majority of methods focus on correcting local errors and miss the global picture. To ad- dress this issue, researchers have developed techniques that incorporate global context and consider the relationships between pixels. Here, we apply persistent homology, a branch of topology that studies the topological structure of shapes, along with deep learning methods to improve the heart segmentation. We use multidimensional topological losses to avoid spurious components and holes and increase the total accuracy. We evaluate the performance of three different approaches: using the dice and pixel-wise losses with the sum of persistences of label diagrams as a regularizer, using the dice and pixel-wise losses with the bottleneck distance as a regularizer, and using both losses without any regularization. We find that, while more computationally demanding, the methods using topological regularizers outperform the other method in terms of accuracy.

Background Understanding the magnitude of cardiovascular disease (CVD) inequalities is the first step toward addressing them. The linkage of socioeconomic and clinical data in universal health care settings provides critical information to characterize CVD inequalities. Methods and Results We employed a prospective cohort design using electronic health records data from all residents of Catalonia aged 18+ between January and December of 2019 (N=6 332 228). We calculated age‐adjusted sex‐specific prevalence of 5 CVD risk factors (diabetes, hypertension, hyperlipidemia, obesity, and smoking), and 4 CVDs (coronary heart disease, cerebrovascular disease, atrial fibrillation, and heart failure). We categorized income into high, moderate, low, and very low according to individual income (tied to prescription copayments) and receipt of welfare support. We found large inequalities in CVD and CVD risk factors among men and women. CVD risk factors with the largest inequalities were diabetes, smoking, and obesity, with prevalence rates 2‐ or 3‐fold higher for those with very low (versus high) income. CVDs with the largest inequalities were cerebrovascular disease and heart failure, with prevalence rates 2 to 4 times higher for men and women with very low (versus high) income. Inequalities varied by age, peaking at midlife (30–50 years) for most diseases, while decreasing gradually with age for smoking. Conclusions We found wide and heterogeneous inequalities by income in 5 CVD risk factors and 4 CVD. Our findings in a region with a high‐quality public health care system and universal coverage stress that strong equity‐promoting policies are necessary to reduce disparities in CVD.

• Several cardiovascular/hemostatic disturbances haves been reported in patients with COVID-19, but the real frequency and their potential association with the pathogenic mechanisms of SARS-CoV-19 still remain to be defined. • We investigated the relative frequency of acute coronary syndrome, deep venous thrombosis, pulmonary embolism, stroke and upper gastrointestinal bleeding in COVID patents attending emergency departments (EDs), before hospitalization and compared them with frequencies in the general ED population attending 50 Spanish EDs. • We found that the risk of pulmonary embolism is clearly increased in COVID patients, with an OR of 4.53 with respect to non-COVID patients (95% confidence interval 4.03- 5.10). Additionally, the diagnosis of pulmonary embolism was 2 fold more frequent among ED comers in 2020 compared to 2019, suggesting a SARS-CoV-2 role in such increment of cases.. The remaining entities studied were not found to be unequivocally increased in the present study and need further investigation.

In situ tissue engineering strategies are a promising approach to activate the endogenous regenerative potential of the cardiac tissue helping the heart to heal itself after an injury. However, the current use of complex reprogramming vectors for the activation of reparative pathways challenges the easy translation of these therapies into the clinic. Here, we evaluated the response of mouse neonatal and human induced pluripotent stem cell-derived cardiomyocytes to the presence of exogenous lactate, thus mimicking the metabolic environment of the fetal heart. An increase in cardiomyocyte cell cycle activity was observed in the presence of lactate, as determined through Ki67 and Aurora-B kinase. Gene expression and RNA-sequencing data revealed that cardiomyocytes incubated with lactate showed upregulation of BMP10, LIN28 or TCIM in tandem with downregulation of GRIK1 or DGKK among others. Lactate also demonstrated a capability to modulate the production of inflammatory cytokines on cardiac fibroblasts, reducing the production of Fas, Fraktalkine or IL-12p40, while stimulating IL-13 and SDF1a. In addition, the generation of a lactate-rich environment improved ex vivo neonatal heart culture, by affecting the contractile activity and sarcomeric structures and inhibiting epicardial cell spreading. Our results also suggested a common link between the effect of lactate and the activation of hypoxia signaling pathways. These findings support a novel use of lactate in cardiac tissue engineering, modulating the metabolic environment of the heart and thus paving the way to the development of lactate-releasing platforms for in situ cardiac regeneration.Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Patient-derived induced pluripotent stem cells (iPSC) are a valuable approach to model cardiovascular diseases. We nucleofected non-integrating episomal vectors in skin fibroblasts of three family members carrying a single nucleotide variant (SNV) in SCN5A, which encodes the cardiac-type sodium channel, and of a related healthy control. The SNV SCN5A_c.4573G > A had been previously identified in a Brugada Syndrome patient. The resulting iPS cell lines differentiate into cells of the 3 germ layers, display normal karyotypes and express pluripotency surface markers and genes. Thus, they are a reliable source to study the effect of the identified mutation in a physiologically relevant environment.

Resumen La evaluacion y prevencion del riesgo cardiovascular (RCV) que persiste en los pacientes con dislipidemia a pesar del tratamiento y de haber alcanzado los objetivos especificos de la concentracion plasmatica de colesterol unido a lipoproteinas de baja densidad (c-LDL) es un reto clinico en la actualidad, y sugiere que los biomarcadores lipidicos convencionales resultan insuficientes para una evaluacion precisa del RCV. Mas alla de su contenido lipidico, existen otras caracteristicas propias de las particulas lipoproteicas que determinan su potencial aterogenico y su influencia en el RCV. Sin embargo, dichas caracteristicas adicionales no pueden ser analizadas por las tecnicas utilizadas habitualmente en los laboratorios clinicos. La espectroscopia por resonancia magnetica nuclear (RMN) es una tecnica que permite un analisis detallado de la cantidad, composicion y tamano de las lipoproteinas y proporciona informacion mas detallada del estado del metabolismo lipidico y del RCV en los pacientes dislipemicos. En este articulo un grupo de lipidologos de la Sociedad Espanola de Arteriosclerosis revisa la evidencia existente sobre los mecanismos aterogenicos de las particulas lipoproteicas y describen el fundamento tecnico y la interpretacion de los perfiles lipoproteicos obtenidos mediante RMN, haciendo especial referencia al test disponible en Espana (Liposcale®). Asimismo, se definen los principales perfiles de pacientes en los que dicho analisis aportaria una informacion de mayor interes clinico, los cuales son: a) sospecha de discordancia entre las concentraciones de lipidos y el numero de particulas, situacion frecuente en la diabetes, la obesidad, el sindrome metabolico y la hipertrigliceridemia; b) enfermedad cardiovascular aterotrombotica (ECVA) precoz o recurrente sin factores de RCV que la justifiquen; c) trastornos lipidicos infrecuentes o complejos como las concentraciones extremas de c-HDL, y d) situaciones clinicas en las que las tecnicas analiticas clasicas no pueden aplicarse, como los valores de c-LDL muy bajos.

[eng] INTRODUCTION: Metabolic syndrome (MetS) is a clustering of different cardiovascular and cardiometabolic risk factors. In developed countries, MetS prevalence has risen to 20- 25% in the adult population, and its incidence is increasing. Public health strategies for MetS treatment and prevention are mainly focused on lifestyle modification, including dietary and physical activity promotion. Aligned with MetS, obesity is a multifactorial complex disease defined by excess of adipose mass, which occurs through adipocyte hypertrophy and hyperplasia. However, while waist circumference is a better predictor for CVD than BMI or body weight, it is an index of total adiposity, and it cannot differentiate visceral from subcutaneous adiposity. The adipose tissue is an endocrine organ that secretes a wide variety of inflammatory adipocytokines, such as TNF-alpha, IL-6, resistin, leptin, and adiponectin. Visceral adiposity is associated with a higher production of these inflammatory adipocytokines, leading to systemic inflammation, insulin resistance, and several obesity-related metabolic disorders. Phenolic compounds, also known as polyphenols, are characterized by the presence of one or more aromatic rings and phenol structural units in its molecules. The main food sources of polyphenols in Mediterranean countries are coffee, fruits, red wine, and vegetable oils, especially olive oil, whereas in non-Mediterranean countries, coffee, tea, fruits, and wine were the main food sources. Moreover, a continuous and prolonged polyphenol intake is related to BP and adiposity lowering effects, improvements in lipid profile, and anti-inflammatory effects, which all act as CVD protectors. OBJECTIVE: The general objective of this thesis project is to evaluate the effect of a high dietary polyphenol intake included in an intensive weight-loss-oriented lifestyle intervention program on adiposity parameters and other cardiovascular risk factors in patients with MetS, as well as the mechanisms involved in these effects. Additionally, we aimed to estimate the dietary polyphenol intake in Spanish population from PREDIMED (PRevención con DIeta MEDiterránea) Plus and validate an updated version of a semi- quantitative food frequency questionnaire. RESULTS: The intake of polyphenol subclasses has been reported to have an impact on MetS components, especially HDL-cholesterol. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. In the case of type 2 diabetes prevalence, catechins, proanthocyanidins, hydroxybenzoic acids, and lignans were inversely associated with type 2 diabetes. These associations were different depending on sex and BMI, that is, women and overweight participants obtained stronger inverse associations. In this sense, after one year of follow-up, increments in total polyphenol intake and some classes were inversely associated with better glucose levels and HbA1c. In the case of body composition, some classes of polyphenols and body adiposity markers determined by dual-energy X-Ray absorptiometry, mainly visceral adipose tissue, and total fat mass after one year of follow-up. When participants were categorized into tertiles according to changes in VAT after one-year of follow-up, an increase of VAT content, showed significant mean increasement in PAI-1, resistin and leptin levels. When comparing among tertiles of VAT showed significant differences in insulin, PAI-1 and c-peptide. Additionally, a validated food frequency questionnaire showed moderate reliability according to Mediterranean diet adherence and biological markers. CONCLUSIONS: In conclusion, dietary polyphenol intake improves MetS criteria, body composition, and obesity-related inflammatory markers and adipokines levels. Improvements in visceral adipose tissue are associated with improvements in cardiometabolic parameters, compared to body weight. Additionally, visceral adipose tissue reductions improvements in obesity-related inflammatory response., [cat] La síndrome metabòlica (MetS) és un agrupament de diferents factors de risc cardiovasculars i cardiometabòlics. Les estratègies de salut pública pel tractament i la prevenció de la MetS es centren principalment en la modificació de l'estil de vida. Dins del marc de la Dieta Mediterrània, els compostos fenòlics també coneguts com a polifenols, han demostrat que una ingesta contínua i prolongada de polifenols està relacionada amb una reducció del risc cardiovascular, incloent la reducció de la pressió arterial, paràmetres d’adipositat, millores en el perfil lipídic i efectes antiinflamatoris. L'objectiu d'aquesta tesi doctoral va ser avaluar l'efecte d'una ingesta de polifenols elevada, dins d’una intervenció d'estil de vida orientat a la pèrdua de pes, sobre paràmetres d'adipositat i altres factors de risc cardiovascular en pacients amb MetS. Addicionalment, estimar la ingesta dietètica de polifenols en la població de l’estudi PREDIMED (PRevención con DIeta MEDiterránea) Plus i validar una versió actualitzada d'un qüestionari de freqüència d’aliments semi-quantitatiu. Les conclusions d’aquesta tesi doctoral inclouen que la ingesta dietètica de polifenols millora els criteris de la MetS, la prevalença de diabetis tipus 2, i la composició corporal, especialment el teixit adipós visceral. A més, la reducció del teixit adipós visceral millora els nivells de paràmetres inflamatoris i adipoquines. Per últim, la validació d’eines de recollida d’informació nutricional amb marcadors biològics i l’adherència a patrons dietètics saludables, com la Dieta Mediterrània, permet classificar als individus en funció de la seva ingesta dietètica.

In December 2019, 27 cases of pneumonia were reported in Wuhan. In 2020, the causative agent was identified as a virus called SARS-CoV-2. The disease was called “coronavirus disease 2019” (COVID-19) and was determined as a Public Health Emergency. The main measures taken to cope with this included a state of lockdown. The aim of this study was to assess how the unhealthy lifestyles that ensued influenced different parameters. A prospective study was carried out on 6236 workers in a Spanish population between March 2019 and March 2021. Anthropometric, clinical, and analytical measurements were performed, revealing differences in the mean values of anthropometric and clinical parameters before and after lockdown due to the pandemic, namely increased body weight (41.1 ± 9.9–43.1 ± 9.9), BMI (25.1 ± 4.7–25.9 ± 4.7), and percentage of body fat (24.5 ± 9.1–26.9 ± 8.8); higher total cholesterol levels, with a statistically significant increase in LDL levels and a reduction in HDL; and worse glucose levels (90.5 ± 16.4–95.4 ± 15.8). Lockdown can be concluded to have had a negative effect on health parameters in both sexes in all age ranges, causing a worsening of cardiovascular risk factors.

Si durante el embarazo el feto experimenta una falta de nutrientes, intentará ahorrar y engordará menos. Sin embargo, esto puede tener importantes consecuencias en su salud adulta.

Computer-aided drug design (CADD) techniques allow the identification of compounds capable of modulating protein functions in pathogenesis-related pathways, which is a promising line on drug discovery. Marine natural products (MNPs) are considered a rich source of bioactive compounds, as the oceans are home to much of the planet’s biodiversity. Biodiversity is directly related to chemodiversity, which can inspire new drug discoveries. Therefore, natural products (NPs) in general, and MNPs in particular, have been used for decades as a source of inspiration for the design of new drugs. However, NPs present both opportunities and challenges. These difficulties can be technical, such as the need to dive or trawl to collect the organisms possessing the compounds, or biological, due to their particular marine habitats and the fact that they can be uncultivable in the laboratory. For all these difficulties, the contributions of CADD can play a very relevant role in simplifying their study, since, for example, no biological sample is needed to carry out an in-silico analysis. Therefore, the amount of natural product that needs to be used in the entire preclinical and clinical study is significantly reduced. Here, we exemplify how this combination between CADD and MNPs can help unlock their therapeutic potential. In this study, using a set of marine invertebrate molecules, we elucidate their possible molecular targets and associated therapeutic potential, establishing a pipeline that can be replicated in future studies.

[cat] La malaltia cardiovascular (MCV) continua essent la primera causa de mortalitat en els països desenvolupats. D‘aquesta manera, la identificació dels factors de risc cardiovasculars (FRCV) i el càlcul del risc d‘esdeveniments cardiovasculars (ECV) són una eina de demostrada efectivitat per a la prevenció primària. L‘aportació de les alteracions de l‘electrocardiograma (ECG) a aquest procés preventiu de detecció d‘individus amb risc de patir ECV és tema d‘estudi i debat, no existint dades en població mediterrània. L‘objectiu primari d‘aquesta tesi doctoral es basa en analitzar l‘associació entre les alteracions majors i menors de l‘ECG en individus amb risc CV mitjà alt i l‘aparició d‘ECV i, determinar si aquesta associació és independent dels FRCV clàssics i la seva contribució a la predicció del risc. Per donar resposta a aquest objectiu primari, els objectius secundaris de la tesis s‘han basat en analitzar si les alteracions de l‘ECG milloren la predicció del risc CV i analitzar aquesta associació en els subgrups d‘homes, dones i individus amb risc CV moderat. Per dur a terme aquesta tesi, els participants es varen seguir durant 9,11 anys. Es varen agafar 1752 participants e l‘estudi PREDIMED, d‘entre 55 i 80 anys amb risc CV mitjà-alt, sense ECV previs i amb ECG inicial. Les alteracions de l‘ECG es basaren en la codificació de Minnesota, incorporant algunes alteracions associades amb la MCV, classificant-les en menors i majors. La variable dependent va ser els ECV (infart agut de miocardi, accident cerebrovascular, mort de causa CV i mort de qualsevol causa). Els principals resultats derivats d'aquesta tesi doctoral van mostrar que les alteracions menors a l‘ECG s‘associen a l‘aparició ECV, encara que deixa de ser estadísticament significativa ajustant per SCORE/SCOREop. Les alteracions majors ajustades per grups d‘aleatorització basal i risc CV, s‘associen amb els ECV de forma estadísticament significativa. En homes, existeix associació entre les alteracions majors i els ECV i individualment per l‘allargament del QTc i el bloqueig auriculoventricular avançat. En dones, existeix associació entre les alteracions majors i els ECV, entre elles el descens patològic de l‘ST i fibril•lació auricular. En individus de risc moderat, les alteracions majors s‘associen amb ECV. Les alteracions majors discriminen la presentació d‘ECV en el conjunt de la mostra, en homes i en dones. La capacitat de discriminació amb AUC al afegir les alteracions majors passa d‘un AUC de 0,677 a un AUC de 0,694 i no és estadísticament significativa. Pel Net reclassification index (NRI) i Integrated Discrimination Improvement (IDI), la modesta millora de la discriminació sí és estadísticament significativa en el conjunt de la mostra i en homes. En conclusió, les alteracions menors de l‘ECG s‘associen amb la presentació d‘ECV, però no son un factor de risc independent. D‘altra banda, les alteracions majors sí són un factor de risc independent. Les següents alteracions majors s‘associen estadísticament amb la presentació d‘ECV: descens patològic de l‘ST, criteris d‘hipertròfia de ventricles esquerra, bloqueig auriculoventricular avançat, allargament de QTc i fibril•lació auricular. Les alteracions majors milloren de forma discreta la capacitat predictiva de la funció SCORE/SCOREop. En homes, les alteracions majors, específicament els criteris d‘hipertròfia de ventricle esquerra, QTc allargat i bloqueig auriculoventricular avançat, s‘associen amb els ECV i la discriminació és major. En dones les alteracions majors, el descens patològic de l‘ST, el bloqueig de branca esquerra i la fibril•lació auricular s‘associen i la discriminació és menor En individus de risc moderat les alteracions majors s‘associen, específicament el bloqueig AV avançat, el QTc i el QRS > 110 mseg, però no milloren la capacitat predictiva del risc CV. [spa] La enfermedad cardiovascular (CV) continúa siendo la primera causa de mortalidad en los países desarrollados. De este modo, la identificación de los factores de riesgo cardiovasculares (FRCV) y el cálculo del riesgo de eventos cardiovasculares (ECV) son una herramienta de demostrada efectividad para la prevención primaria. La aportación de las alteraciones del electrocardiograma (ECG) a este proceso preventivo de detección de individuos con riesgo de sufrir enfermedad CV es tema de estudio y debate, no existiendo datos en población mediterránea. El objetivo primario de esta tesis doctoral se basa en analizar la asociación entre las alteraciones mayores y menores del ECG en individuos con riesgo CV mediano alto y la aparición de ECV y, determinar si esta asociación es independiente de los FRCV clásicos y su contribución a la predicción del riesgo. Para dar respuesta a este objetivo primario, los objetivos secundarios de la tesis se han basado en analizar si las alteraciones del ECG mejoran la predicción del riesgo CV y analizar esta asociación en los subgrupos de hombres, mujeres e individuos con riesgo CV moderado. Para llevar a cabo esta tesis, los participantes se siguieron durante 9,11 años. Se cogieron 1752 participantes del estudio PREDIMED, de entre 55 y 80 años con riesgo CV mediano-alto, sin ECV previo y con ECG inicial. Las alteraciones del ECG se basaron en la codificación de Minnesota, incorporando algunas alteraciones asociadas con la enfermedad CV, clasificándolas en menores y mayores. La variable dependiente fue los ECV (infarto agudo de miocardio, accidente cerebrovascular, muertes de causa CV y muertes por cualquier causa). Los principales resultados derivados de esta tesis doctoral mostraron que las alteraciones menores del ECG se asocian a la aparición de ECV, aunque deja de ser estadísticamente significativa ajustando por SCORE/SCOREop. Las alteraciones mayores ajustadas por grupos de aleatorización basal y riesgo CV, se asocian con los eventos CV de forma estadísticamente significativa. En hombres, existe asociación entre las alteraciones mayores y los ECV, e individualmente por el alargamiento del QTc y el bloqueo auriculoventricular avanzado. En mujeres, existe asociación entre las alteraciones mayores y los ECV, entre ellas en descenso patológico del ST y fibrilación auricular. En individuos de riesgo moderado, las alteraciones mayores se asocian con ECV. Las alteraciones mayores discriminan la presentación del ECV en el conjunto de la muestra, en hombres y en mujeres. La capacidad de discriminación con AUC al añadir las alteraciones mayores pasa de un AUC de 0,677 a un AUC de 0,694 y no es estadísticamente significativa. Por el Net reclassification index (NRI) y Integrated Discrimination Improvement (IDI), la modesta mejora de la discriminación sí es estadísticamente significativa en el conjunto de la muestra y en hombres. En conclusión, las alteraciones menores del ECG se asocian con la presentación de ECV, pero no son un factor de riesgo independiente. Por otro lado, las alteraciones mayores sí son un factor de riesgo independiente. Las siguientes alteraciones mayores se asocian estadísticamente con la presentación de ECV: descenso patológico del ST, criterios de hipertrofia de ventrículos izquierda, bloqueo auriculoventricular avanzado, alargamiento de QTc y fibrilación auricular. Las alteraciones mayores mejoran de forma discreta la capacidad predictiva de la función SCORE/SCOREop. En hombres, las alteraciones mayores, específicamente los criterios de hipertrofia de ventrículo izquierda, QTc alargado y bloqueo auriculoventricular avanzado, se asocian con los ECV, siendo la discriminación mayor. En mujeres, las alteraciones mayores, el descenso patológico del ST, el bloqueo de rama izquierda y la fibrilación auricular se asocian a ECV y la discriminación es menor. En individuos de riesgo moderado las alteraciones mayores se asocian a ECV, específicamente el bloqueo AVV avanzado, el QTc y el QRS > 110 mseg, pero no mejoran la capacidad predictiva del riesgo CV. [eng] Cardiovascular (CV) disease is the leading cause of mortality in developed countries. Therefore, the identification of cardiovascular risk factors (CVRF), as well as calculating the risk of cardiovascular events are a tool of proven effectiveness for primary prevention. The contribution of electrocardiogram (ECG) alterations to the preventive process of detecting individuals at risk of CV disease is still under debate, with no data in the Mediterranean population. For the aforementioned reasons, the general purpose of this doctoral thesis is based on analyzing the association between major and minor ECG alterations in individuals with medium-high CV risk, analyzing the onset of CV disease and determining whether this association is independent of classic CVRF, and its contribution to the risk prediction. In order to answer this primary objective, the secondary objectives of the thesis are based on analyzing whether ECG alterations improve the prediction of CV risk and analyzing this association in the subgroups of men, women and individuals with moderate CV risk. Participants were followed for 9.11 years. 1752 participants with initial ECG were obtained from the PREDIMED study, between 55 and 80 years old with medium-high CV risk, without previous CV disease. ECG alterations were based on the Minnesota coding, incorporating some alterations associated with CV disease, classifying them into minor and major alterations. The dependent variable was CV disease (acute myocardial infarction, stroke, CV deaths, and deaths from any other cause). The main findings derived from this dissertation showed that minor ECG alterations are associated with the onset of CV disease, although they are no longer statistically significant when adjusting for SCORE / SCOREop. Major alterations adjusted for baseline randomization and CV risk groups are statistically significantly associated with CV events. In men, there is an association between major alterations and CV disease, specifically due to QTc lengthening and advanced atrioventricular block. In women, there is an association between major alterations and CV disease, including pathological descent of the ST and atrial fibrillation. In moderate-risk individuals, major abnormalities are associated with CV disease. The major alterations discriminate the presence of CV disease in men, women and in the whole sample. The ability to discriminate with AUC when adding the major alterations varies from an AUC of 0.677 to an AUC of 0.694, being not statistically significant. By the Net reclassification index (NRI) and Integrated Discrimination Improvement (IDI), the modest improvement in discrimination is statistically significant in the whole sample and in men. In conclusion, minor ECG abnormalities are associated with the development of CV disease but are not independent risk factors. On the other hand, major alterations are independent risk factors. The following major alterations are statistically associated with the onset of CV disease: pathological ST descent, criteria for left ventricular hypertrophy, advanced atrioventricular block, QTc lengthening, and atrial fibrillation. Major alterations discreetly improve the predictive ability of the SCORE / SCOREop function. In men, major alterations, specifically the criteria of left ventricular hypertrophy, lengthened QTc, and advanced atrioventricular block, are associated with CV disease, with greater discrimination. In women, major alterations, pathological ST descent, left bundle branch block, and atrial fibrillation are associated with CV disease, with less discrimination. In moderate-risk individuals, major alterations are associated with CV disease, specifically advanced AVV block, QTc and QRS> 110 msec, but they do not improve the predictive capacity of CV risk.

Phenol-rich foods consumption such as virgin olive oil (VOO) has been shown to have beneficial effects on cardiovascular diseases. The broader biochemical impact of VOO and phenol-enriched OOs remains, however, unclear. A randomized, double-blind, cross-over, controlled trial was performed with thirty-three hypercholesterolemic individuals who ingested for 3-weeks (25 mL/day): (1) an OO enriched with its own olive oil phenolic compounds (PCs) (500 ppm; FOO); (2) an OO enriched with its own olive oil PCs (250 ppm) plus thyme PCs (250 ppm; FOOT); and (3) a VOO with low phenolic content (80 ppm). Serum lipid and glycemic profiles, serum 1H-NMR spectroscopy-based metabolomics, endothelial function, blood pressure, and cardiovascular risk were measured. We combined OPLS-DA with machine learning modelling to identify metabolites discrimination of the treatment groups. Both phenol-enriched OO interventions decreased the levels of glutamine, creatinine, creatine, dimethylamine, and histidine in comparison to VOO one. In addition, FOOT decreased the plasma levels of glycine and DMSO2 compared to VOO, while FOO decreased the circulating alanine concentrations but increased the plasma levels of acetone and 3-HB compared to VOO. Based on these findings, phenol-enriched OOs were shown to result in a favorable shift in the circulating metabolic phenotype, inducing a reduction in metabolites associated with cardiometabolic diseases. It was supported by the Spanish Ministry of Science and Innovation (MICINN) financing the projects AGL2009-13517-C03-01, AGL2009-13517-C03-02, AGL2009-13517-C03-03, and AGL2012-40144-C03-01. It was also supported by the Instituto de Salud Carlos III (Co-funded by the European Regional Development Fund [ERDF], a way to build Europe), financing the CIBEROBN-stay fellowship and Sara Borrell contract (CD17/00233) to M. Farràs. The PI1800164 project to F.B.-V, and the PI20/01090 project, and the Miguel Servet Program to J.M.-P. CIBERCV, CIBERDEM, and CIBEROBN are initiatives of Instituto de Salud Carlos III.

Objetivo Durante los años 2019 y 2020 se realizaró una serie de reuniones en todo el territorio nacional dirigidas a explicar la metodología y los criterios de elaboración de las recomendaciones sobre la utilización de iPCSK9 publicadas por la Sociedad Española de Arteriosclerosis. Al final de cada una de las reuniones se realizó una encuesta entre los médicos participantes dirigida a describir los requerimientos de prescripción de estos fármacos en las diferentes regiones españolas. Metodología El Proyecto Efecto Mariposa fue desarrollado por un comité científico experto en lipídos. Tras la elaboración de todos los materiales necesarios para llevar a cabo el proyecto, se efectuó una reunión de formadores, impartida por los coordinadores del proyecto, a un total de 17 expertos. Posteriormente, se realizaron 16 talleres regionales con la asistencia de 169 médicos implicados en el manejo de la hipercolesterolemia, los cuales respondieron una encuesta donde se planteaban diferentes cuestiones acerca del uso de los iPCSK9 en su práctica clínica. Resultados Hubo una gran heterogeneidad entre centros en cuanto a los requerimientos y dificultades para la prescripción de iPCSK9. Un 21% de los encuestados indicaron tener dificultades escasas para prescribir iPCSK9 en su hospital, mientras que el 78% encontraba dificultades moderadas o elevadas. Las dificultades procedían en un 18% de aspectos burocrático-administrativos, en un 41% de restricciones en su indicación y en un 38% de ambas. En general, los obstáculos encontrados no dependían del nivel del hospital, de la especialidad ni de la presencia de unidades homologadas de lípidos, si bien la existencia de esta última se asociaba a un mayor número de pacientes tratados con iPCSK9. Los factores asociados con una mayor dificultad en la prescripción fueron: la presencia de una comisión de aprobación, la frecuencia de revisión del tratamiento activo por parte de la farmacia hospitalaria, la cadencia temporal de la prescripción, el perfil de pacientes atendidos y los criterios seguidos por los especialistas para la prescripción. Conclusión Los resultados demuestran importantes diferencias en el tratamiento con iPCSK9 en el contexto de la práctica clínica habitual en España. El análisis de estos resultados permitirá plantear en el futuro actuaciones orientadas a la equidad del acceso a los iPCSK9 a nivel nacional, con el objetivo principal de maximizar su beneficio potencial de acuerdo con el perfil del paciente.

Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention. Plasma concentrations of carotenoids were quantified by liquid chromatography coupled to mass spectrometry. The associations between carotenoid concentrations and cardiometabolic risk factors were assessed using regression models adapted for interval-censored variables. Carotenoid concentrations were cross-sectionally inversely associated with serum triglyceride concentrations [-2.79 mg/dl (95% CI: -4.25, -1.34) and -5.15 mg/dl (95% CI: -7.38, -2.93), p-values = 0.0002 and, (AGL2016-75329-R and PID2020- 114022RB-I0) Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades, (AEI/FEDER 10.13039/501100011033, UE), Generalitat de Catalunya (GC) (2017SGR196, 2017SGR622), PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, PI20/01158, European Research Council (Advanced Research Grant 2014–2019; agreement #340918), Recercaixa (number 2013ACUP00194), Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018), PROMETEO/2017/017 grant from the Generalitat Valenciana, SEMERGEN grant, ICREA, FPU17/00513

FIS grants 17/1709, 20/144, PI20/00564 and PIE16/00022 (Instituto de Salud Carlos III, State Secretary of R+D+I, and FEDER/FSE), PNSD (2020/021), the CIBERESP, the CIBERCV and CIBEROBN (Instituto de Salud Carlos III)., Background & aims: The specific association of olive oil consumption with coronary heart disease (CHD) or stroke has not been totally established. Objective: to examine whether olive oil consumption is associated with subclinical atherosclerosis, the risk of total cardiovascular disease (CVD), CHD, and stroke. Methods: Three cohorts were included: AWHS (2318 men), SUN Project (18,266 men and women), and EPIC-Spain (39,393 men and women). Olive oil consumption was measured at baseline using validated questionnaires. Results: In the AWHS, 747 participants had a positive coronary artery calcium score (CACS>0), and the OR (95% CI) was 0.89 (0.72, 1.10) in those with virgin olive oil consumption ≥30 g/day (v., CIBERESP, State Secretary of R+D+I, Faculty of Science and Engineering, University of Manchester, Plan Nacional sobre Drogas 2020/021, Instituto de Salud Carlos III, European Regional Development Fund, Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Age is associated with increased cardiovascular risk factors and cardiovascular disease, which constitutes the leading cause of morbidity and mortality in elderly population. In this text we thoroughly review current evidence regarding the impact on cardiovascular disease of the most important cardiovascular risk factors, especially prevalent and common in the elderly population. Diagnosis and treatment approaches are also addressed, also highlighting the importance of adequate primary and secondary prevention and management. Also, the relationship between cardiovascular disease and some comorbidities and geriatric conditions, such as frailty, particularly common in the elderly, is reviewed, together with some other issues, less often addressed but closely related to ageing, such as genetics, structural and electrical heart changes and oxidative stress. All such questions are of great importance in the comprehensive approach of risk factors and cardiovascular disease in the elderly. Sin financiación 4.430 JCR (2021) Q2, 57/143 Cardiac & Cardiovascular Systems 0.590 SJR (2021) Q2, 158/356 Cardiology and Cardiovascular Medicine No data IDR 2021 UEM

Background Restricted outdoor activity during COVID-19 related lockdown may accelerate heart failure (HF) progression and thereby increase cardiac arrhythmias. We analyzed the impact of March/April 2020 lockdown on physical activity and arrhythmia burden in HF patients treated with cardiac resynchronization therapy (CRT) devices with daily, automatic remote monitoring (RM) function. Methods The study cohort included 405 HF patients enrolled in Observation of Clinical Routine Care for Heart Failure Patients Implanted with BIOTRONIK CRT Devices (BIO|STREAM.HF) registry in 16 countries, who had left ventricular ejection fraction (LVEF) = 8 min/day in 46.5% of patients; predictors were higher LVEF, lower NYHA class, no defibrillator indication, and more activity before lockdown. AHRE burden increased by >= 17 min/day in 4.7% of patients; predictors were history of atrial fibrillation, higher LVEF, higher body mass index, and activity decrease during lockdown. Conclusion Unfavorable changes in physical activity, AHRE burden, and follow-up rate were observed during lockdown, but not in ventricular arrhythmia.

Background Non-communicable diseases (NCDs) account for 71% of deaths worldwide and individual behaviours such as sedentariness play an important role on their development and management. However, the detrimental effect of daily sitting on multiple NCDs has rarely been studied. This study sought (i) to investigate the association between sitting time and main NCDs and multimorbidity in the population of Catalonia and (ii) to explore the effect of physical activity as a modifier of the associations between sitting time and health outcomes. Methods Cross-sectional data from the 2016 National Health Survey of Catalonia were analyzed, and multivariable logistic regression, adjusting for socio-demographics and individual risk factors (tobacco and alcohol consumption, diet, hyperlipidaemia, hypertension, body mass index) was used to estimated odds ratios (ORs) and 95% confidence intervals (CIs) of the association between sitting time and NCDs. Results A total of 3320 people ≥15 years old were included in the study. Sitting more than 5 h/day was associated with a higher risk of cardiovascular disease (OR 1.90, 95% CI: 1.21–2.97), respiratory disease (OR 1.61, 95% CI: 1.13–2.30) and multimorbidity (OR 2.80, 95% CI: 1.53–5.15). Sitting more than 3 h/day was also associated with a higher risk of multimorbidity (OR 2.26, 95% CI: 1.23–4.16). Physical activity did not modify the associations between sitting time and any of the outcomes. Conclusions Daily sitting time might be an independent risk factor for some NCDs, such as cardiovascular disease, respiratory disease and multimorbidity, independently of the level risk of physical inactivity.

Planning and prioritizing resource allocation in prevention and patient care depends on availability of information on the evolution of incidence and mortality rates, case-fatality, and other related factors regarding the diseases with the greatest population impact on public health.1 One example of the importance of having access to quality information is our need to understand cardiovascular diseases (CVD) and the associated risk factors. Indeed, CVD remains the most common cause of death in Europe with >60 million potential years of life lost to CVD in Europe annually.

Background and objective: Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, with a greater incidence in the most disadvantaged social classes. In this study, we aimed to evaluate the level of cardiovascular risk in cleaning workers. Methods: This was a descriptive, cross-sectional study in 46.632 cleaning workers (40.169 women and 6.463 men). Thirty-one different scales related to cardiovascular risk were studied (14 assessing overweight and obesity, 5 determining the risk of nonalcoholic fatty liver disease, 5 scales of cardiovascular risk, 4 atherogenic indices, and 3 scales of metabolic syndrome, among others). The results obtained were divided between personnel who perform their cleaning tasksin the hotel and catering industry and those in other sectors. Results: The prevalence of obesity and arterial hypertension in cleaning workers was over 20% in both sexes. A similar amount was observed in moderate or high values on the REGICOR (Registre GIroní del COR) scale. More than 15% presented metabolic syndrome according to the NCEP ATPIII (National Cholesterol Education Program-Adult Treatment Program III) criteria, while over 10% of women and 20% of men had a high risk of nonalcoholic fatty liver disease assessed with the fatty liver index. Conclusion: Cardiovascular risk is higher, in both sexes, in the group of cleaning workers who work in companies other than hotels.

BACKGROUND: Cardio-vascular disease and depression are thought to be closely related, due to shared risk factors. The aim of the study was to determine the association between cardio-vascular risk (CVR) factors and depressive status in a population (55-75 years) with metabolic syndrome (MetS) from the PREDIMED-Plus trial. METHODS AND FINDINGS: Participants were classified into three groups of CVR according to the Framingham-based REGICOR function: (1) low (LR), (2) medium (MR) or (3) high/very high (HR). The Beck Depression Inventory-II (BDI-II) was used to assess depressive symptoms at baseline and after 2 years. The association between CVR and depressive status at baseline (n = 6545), and their changes after 2 years (n = 4566) were evaluated through multivariable regression models (logistic and linear models). HR women showed higher odds of depressive status than LR [OR (95% CI) = 1.78 (1.26, 2.50)]. MR and HR participants with total cholesterol

Myocardial infarction is the main driver of heart failure due to ischemia and subsequent cell death, and cell-based strategies have emerged as promising therapeutic methods to replace dead tissue in cardiovascular diseases. Research in this field has been dramatically advanced by the development of laboratory-induced pluripotent stem cells (iPSCs) that harbor the capability to become any cell type. Like other experimental strategies, stem cell therapy must meet multiple requirements before reaching the clinical trial phase, and in vivo models are indispensable for ensuring the safety of such novel therapies. Specifically, translational studies in large animal models are necessary to fully evaluate the therapeutic potential of this approach; to empirically determine the optimal combination of cell types, supplementary factors, and delivery methods to maximize efficacy; and to stringently assess safety. In the present review, we summarize the main strategies employed to generate iPSCs and differentiate them into cardiomyocytes in large animal species; the most critical differences between using small versus large animal models for cardiovascular studies; and the strategies that have been pursued regarding implanted cells’ stage of differentiation, origin, and technical application.

Mortality from cardiovascular disease (CVD), second tumours, and other causes is of clinical interest in the long-term follow-up of breast cancer (BC) patients. Using a cohort of BC patients (N = 6758) from the cancer registries of Girona and Tarragona (north-eastern Spain), we studied the 10-year probabilities of death due to BC, other cancers, and CVD according to stage at diagnosis and hormone receptor (HR) status. Among the non-BC causes of death (N = 720), CVD (N = 218) surpassed other cancers (N = 196). The BC cohort presented a significantly higher risk of death due to endometrial and ovarian cancers than the general population. In Stage I, HR− patients showed a 1.72-fold higher probability of all-cause death and a 6.11-fold higher probability of breast cancer death than HR+ patients. In Stages II–III, the probability of CVD death (range 3.11% to 3.86%) surpassed that of other cancers (range 0.54% to 3.11%). In Stage IV patients, the probability of death from any cancer drove the mortality risk. Promoting screening and preventive measures in BC patients are warranted, since long-term control should encompass early detection of second neoplasms, ruling out the possibility of late recurrence. In patients diagnosed in Stages II–III at an older age, surveillance for preventing late cardiotoxicity is crucial.

Heart failure (HF) is a clinical syndrome characterized by the presence of dyspnea or limited exertion due to impaired cardiac ventricular filling and/or blood ejection. Because of its high prevalence, it is a major health and economic burden worldwide. Several mechanisms are involved in the pathophysiology of HF. First, the renin-angiotensin-aldosterone system (RAAS) is over-activated, causing vasoconstriction, hypertension, elevated aldosterone levels and sympathetic tone, and eventually cardiac remodeling. Second, an endogenous compensatory mechanism, the natriuretic peptide (NP) system is also activated, albeit insufficiently to counteract the RAAS effects. Since NPs are degraded by the enzyme neprilysin, it was hypothesized that its inhibition could be an important therapeutic target in HF. Sacubitril/valsartan is the first of the class of dual neprilysin and angiotensin receptor inhibitors (ARNI). In patients with HFrEF, treatment with sacubitril/valsartan has demonstrated to significantly reduce mortality and the rates of hospitalization and rehospitalization for HF when compared to enalapril. This communication reviews in detail the demonstrated benefits of sacubitril/valsartan in the treatment of patients with HFrEF, including reduction of mortality and disease progression as well as improvement in cardiac remodeling and quality of life. The hemodynamic and organic effects arising from its dual mechanism of action, including the impact of neprilysin inhibition at the renal level, especially relevant in patients with type 2 diabetes mellitus, are also reviewed. Finally, the evidence on the demonstrated safety and tolerability profile of sacubitril/valsartan in the different subpopulations studied has been compiled. The review of this evidence, together with the recommendations of the latest clinical guidelines, position sacubitril/valsartan as a fundamental pillar in the treatment of patients with HFrEF.

The authors wish to thank the PREDIMED-Plus participants and staff for their engagement, as well as to the primary care centers involved in the study. We also thank the Cerca Programme of the Generalitat de Catalunya, and the CIBEROBN, CIBERESP and CIBERDEM initiatives of Instituto de Salud Carlos III in Spain, and the collaborators in the PRIME consortium for helpful input. The first version of the present article has been published in the public repository Research Square as a preprint publication of our work (44). We particularly thank Stephanie Nishi for her assistance with manuscript language revision., Introduction: Type 2 diabetes has been linked to greater cognitive decline, but other glycemic parameters such as prediabetes, diabetes control and treatment, and HOMA-IR and HbA1c diabetes-related biomarkers have shown inconsistent results. Furthermore, there is limited research assessing these relationships in short-term studies. Thus, we aimed to examine 2-year associations between baseline diabetes/glycemic status and changes in cognitive function in older participants at high risk of cardiovascular disease. Methods: We conducted a 2-year prospective cohort study (n=6,874) within the framework of the PREDIMED-Plus study. The participants (with overweight/obesity and metabolic syndrome; mean age 64.9 years; 48.5% women) completed a battery of 8 cognitive tests, and a global cognitive function Z-score (GCF) was estimated. At baseline, participants were categorized by diabetes status (no-diabetes, prediabetes, and, CIBERESP, Generalitat de Catalunya, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

BackgroundSkeletal muscle mass (SMM) is inversely associated with cardiometabolic health and the ageing process. The aim of the present work was to evaluate the relation between SMM and 10 year cardiovascular disease (CVD) incidence, among CVD-free adults 45+ years old.MethodsATTICA is a prospective, population-based study that recruited 3042 adults without pre-existing CVD from the Greek general population (Caucasians; age ≥18 years; 1514 men). The 10 year study follow-up (2011–2012) captured the fatal/non-fatal CVD incidence in 2020 participants (50% men). The working sample consisted of 1019 participants, 45+ years old (men: n=534; women: n=485). A skeletal muscle mass index (SMI) was created to reflect SMM, using appendicular skeletal muscle mass (ASM) standardised by body mass index (BMI). ASM and SMI were calculated with specific indirect population formulas.ResultsThe 10 year CVD incidence increased significantly across the baseline SMI tertiles (pConclusionsThe presented findings support the importance of SMM evaluation in the prediction of long-term CVD risk among adults 45+ years old without pre-existing CVD. Preservation of SMM may contribute to CVD health.

Cardiovascular diseases (CVDs) affect the myocardium and vasculature, inducing remodelling of the heart from cellular to whole organ level. To assess their impact at micro and macroscopic level, multi-resolution imaging techniques that provide high quality images without sample alteration and in 3D are necessary: requirements not fulfilled by most of current methods. In this paper, we take advantage of the non-destructive time-efficient 3D multiscale capabilities of synchrotron Propagation-based X-Ray Phase Contrast Imaging (PB-X-PCI) to study a wide range of cardiac tissue characteristics in one healthy and three different diseased rat models. With a dedicated image processing pipeline, PB-X-PCI images are analysed in order to show its capability to assess different cardiac tissue components at both macroscopic and microscopic levels. The presented technique evaluates in detail the overall cardiac morphology, myocyte aggregate orientation, vasculature changes, fibrosis formation and nearly single cell arrangement. Our results agree with conventional histology and literature. This study demonstrates that synchrotron PB-X-PCI, combined with image processing tools, is a powerful technique for multi-resolution structural investigation of the heart ex-vivo. Therefore, the proposed approach can improve the understanding of the multiscale remodelling processes occurring in CVDs, and the comprehensive and fast assessment of future interventional approaches., Scientific Reports, 9, ISSN:2045-2322

Background: Selenium is an essential trace mineral with potential interest for cardiovascular disease (CVD) prevention owing to its antioxidant properties. Epidemiological data on selenium status and CVD remain inconsistent. The objective of this study was to ascertain whether low serum selenium (SSe) concentrations are related to an increased risk of a first CVD event in a population at high cardiovascular risk. Methods: We undertook a case-control study nested within the “PREvención con DIeta MEDiterránea” (PREDIMED) trial. A total of 207 participants diagnosed with CVD (myocardial infarction, stroke, or cardiovascular death) during the follow-up period (2003–2010) were matched by sex, age, and intervention group to 436 controls by incidence density sampling. Median time between serum sample collection and subsequent CVD event occurrence was 0.94 years. SSe levels were determined using inductively coupled plasma mass spectrometry analysis. Covariates were assessed through validated questionnaires, in-person interviews, and medical record reviews. Conditional logistic regression was used to calculate multivariable-adjusted odds ratios (ORs). Results: Among women, the mean SSe concentration was lower in cases than in controls (98.5 g/L vs. 103.8 g/L; p = 0.016). In controls, SSe levels were directly associated with percentage of total energy intake from proteins and fish intake (p for linear trend < 0.001 and 0.049, respectively), whereas SSe concentrations were inversely associated with age, body mass index, and percentage of total energy intake from carbohydrates (p for linear trend < 0.001, 0.008 and 0.016 respectively). In the total group, we observed an inverse dose–response gradient between SSe levels and risk of CVD in the fully-adjusted model (highest vs. lowest quartile: OR = 0.47, 95% CI: 0.27–0.81; ptrend = 0.003). Conclusions: Among elderly individuals at high cardiovascular risk, high SSe concentrations within population reference values are associated with lower first CVD incidence., official funding agency for biomedical research of the Spanish government, Instituto de Salud Carlos III (ISCIII) RTIC G03/140, RTIC RD 06/0045 "PREDIMED" JR14/00008, Spanish government, Instituto de Salud Carlos III (ISCIII), through Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Centro Nacional de Investigaciones Cardiovasculares CNIC 06/2007, Fondo de Investigacion Sanitaria-Fondo Europeo de Desarrollo Regional (Proyecto de Investigacion) PI04-2239 PI05/2584 CP06/00100 PI07/0240 PI07/1138 PI07/0954 PI 07/0473 PI10/01407 PI10/02658 PI11/01647 P11/02505 PI13/00462, Ministry of Science and Innovation, Spain (MICINN) (AGL)-2009-13906-C02 AGL2010-22319-C03 AGL2013-49083C3-1-R, Ministerio de Economia y Competitividad-Fondos FEDER-Instituto de Salud Carlos III UNGR15-CE-3380 Fundacion Mapfre 2010, Junta de Andalucia PI0105/2007, Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Center for Forestry Research & Experimentation (CIEF) GVACOMP 06109 GVACOMP2010-181 GVACOMP2011-151 PROMETEO 21/2021, Conselleria de Sanitat y Atencion Primaria CS2010-AP-111 CS2011-AP-042, Regional Government of Navarra P27/2011, Centre Catala de la Nutricio de l'Institut d'Estudis Catalans

Background: Diabesity is a growing problem internationally. Taking into account the importance of physical activity and diet in its prevention and treatment, the objective of this study was to delve into the impact of healthy habits on diabesity. Methods: A descriptive, cross-sectional study was carried out in 386,924 Spanish adult workers. Obesity was determined according to eleven different formulas. Life habits were also valued; sociodemographic variables; and educational level; as well as analytical and clinical variables such as blood pressure and blood glucose levels. The association between the different variables was performed using the chi-square and the Student’s t-tests when the samples were independent. A multivariate analysis was performed using the multinomial logistic regression test by calculating the odds ratio and a 95% confidence interval. The Hosmer–Lemeshow goodness-of-fit test was also performed. Results: The overall prevalence of diabesity ranged between 0.3% (95% CI 0.3–0.4) when obesity was assessed according to the abdominal volume index and 8.3% (95% CI 8.2–8.4) when evaluated according to the CUN-BAE (Clínica Universitaria de Navarra Body Adiposity Estimator) formula. The prevalence of diabesity was also higher in workers with a non-heart-healthy diet and in those who did not exercise regularly. Conclusions: The most disadvantaged socioeconomic classes are those with the highest prevalence of diabesity. It is important to prioritise prevention in populations and communities with the most unfavourable social and environmental conditions to reduce the burden of diabesity.

LThis work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS), which is co-funded by the European Regional Development Fund (six coordinated FIS projects leaded by JS-S and JVi, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, PI20/01158); the Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant to JS-S; the European Research Council (Advanced Research Grant 2014-2019; agreement #340918) granted to MAM-G.; the Recercaixa (number 2013ACUP00194) grant to JS-S; grants from the Consejeria de Salud de la Junta de Andalucia (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; the SEMERGEN grant; None of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication., Purpose We explored the cross-sectional association between the adherence to three different provegetarian (PVG) food patterns defined as general (gPVG), healthful (hPVG) and unhealthful (uPVG), and the cardiometabolic risk in adults with metabolic syndrome (MetS) of the PREDIMED-Plus randomized intervention study. Methods We performed a cross-sectional analysis of baseline data from 6439 participants of the PREDIMED-Plus randomized intervention study. The gPVG food pattern was built by positively scoring plant foods (vegetables/fruits/legumes/ grains/potatoes/nuts/olive oil) and negatively scoring, animal foods (meat and meat products/animal fats/eggs/fish and seafood/dairy products). The hPVG and uPVG were generated from the gPVG by adding four new food groups (tea and coffee/ fruit juices/sugar-sweetened beverages/sweets and desserts), splitting grains and potatoes and scoring them differently. Multivariable-adjusted robust linear regression using MM-type estimator was used to assess the association between PVG food patterns and the standardized Metabolic Syndrome score (MetS z-score), a composed index that has been previously used to ascertain the cardiometabolic risk, adjusting for potential confounders. Results A higher adherence to the gPVG and hPVG was associated with lower cardiometabolic risk in multivariable models. The regression coefficients for 5th vs. 1st quintile were − 0.16 (95% CI: − 0.33 to 0.01) for gPVG (p trend: 0.015), and − 0.23 (95% CI: − 0.41 to − 0.05) for hPVG (p trend: 0.016). In contrast, a higher adherence to the uPVG was associated with higher cardiometabolic risk, 0.21 (95% CI: 0.04 to 0.38) (p trend: 0.019). Conclusion Higher adherence to gPVG and hPVG food patterns was generally associated with lower cardiovascular risk, whereas higher adherence to uPVG was associated to higher cardiovascular risk., official Spanish Institutions, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS), European Commission PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206 PI14/01919 PI14/00853 PI14/01374, The European Regional Development Fund PI14/00972 PI14/00728 PI14/01471 PI16/00473 PI16/00662 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215, European Commission PI17/01441 PI17/00508 PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576 PI19/00017 PI19/01226 PI19/00781 PI19/01560 PI19/01332 PI20/01802 PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158, Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant, European Research Council (ERC), European Commission 340918, La Caixa Foundation 2013ACUP00194, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Generalitat Valenciana European Commission PROMETEO/2017/017, SEMERGEN grant

Importance: Premature death from all causes and cardiovascular disease (CVD) causes is higher among persons with diabetes. Objective: To investigate the association between time spent cycling and all-cause and CVD mortality among persons with diabetes, as well as to evaluate the association between change in time spent cycling and risk of all-cause and CVD mortality. Design, setting, and participants: This prospective cohort study included 7459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition study. Questionnaires regarding medical history, sociodemographic, and lifestyle information were administered in 10 Western European countries from 1992 through 2000 (baseline examination) and at a second examination 5 years after baseline. A total of 5423 participants with diabetes completed both examinations. The final updated primary analysis was conducted on November 13, 2020. Exposures: The primary exposure was self-reported time spent cycling per week at the baseline examination. The secondary exposure was change in cycling status from baseline to the second examination. Main outcomes and measures: The primary and secondary outcomes were all-cause and CVD mortality, respectively, adjusted for other physical activity modalities, diabetes duration, and sociodemographic and lifestyle factors. Results: Of the 7459 adults with diabetes included in the analysis, the mean (SD) age was 55.9 (7.7) years, and 3924 (52.6%) were female. During 110 944 person-years of follow-up, 1673 deaths from all causes were registered. Compared with the reference group of people who reported no cycling at baseline (0 min/wk), the multivariable-adjusted hazard ratios for all-cause mortality were 0.78 (95% CI, 0.61-0.99), 0.76 (95% CI, 0.65-0.88), 0.68 (95% CI, 0.57-0.82), and 0.76 (95% CI, 0.63-0.91) for cycling 1 to 59, 60 to 149, 150 to 299, and 300 or more min/wk, respectively. In an analysis of change in time spent cycling with 57 802 person-years of follow-up, a total of 975 deaths from all causes were recorded. Compared with people who reported no cycling at both examinations, the multivariable-adjusted hazard ratios for all-cause mortality were 0.90 (95% CI, 0.71-1.14) in those who cycled and then stopped, 0.65 (95% CI, 0.46-0.92) in initial noncyclists who started cycling, and 0.65 (95% CI, 0.53-0.80) for people who reported cycling at both examinations. Similar results were observed for CVD mortality. Conclusion and relevance: In this cohort study, cycling was associated with lower all-cause and CVD mortality risk among people with diabetes independent of practicing other types of physical activity. Participants who took up cycling between the baseline and second examination had a considerably lower risk of both all-cause and CVD mortality compared with consistent noncyclists.

Postmenopausal women are at higher risk of developing cardiovascular diseases due to changes in lipid profile and body fat, among others. The aim of this study was to evaluate the association of urinary tartaric acid, a biomarker of wine consumption, with anthropometric (weight, waist circumference, body mass index (BMI), and waist-to-height ratio), blood pressure, and biochemical variables (blood glucose and lipid profile) that may be affected during the menopausal transition. This sub-study of the PREDIMED (Prevención con Dieta Mediterránea) trial included a sample of 230 women aged 60–80 years with high cardiovascular risk at baseline. Urine samples were diluted and filtered, and tartaric acid was analyzed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Correlations between tartaric acid and the study variables were adjusted for age, education level, smoking status, physical activity, BMI, cholesterol-lowering, antihypertensive, and insulin treatment, total energy intake, and consumption of fruits, vegetables, and raisins. A strong association was observed between wine consumption and urinary tartaric acid (0.01 μg/mg (95% confidence interval (CI): 0.01, 0.01), p-value &lt, 0.001). Total and low-density lipoprotein (LDL) cholesterol were inversely correlated with urinary tartaric acid (−3.13 μg/mg (−5.54, −0.71), p-value = 0.016 and −3.03 μg/mg (−5.62, −0.42), p-value = 0.027, respectively), whereas other biochemical and anthropometric variables were unrelated. The results suggest that wine consumption may have a positive effect on cardiovascular health in postmenopausal women, underpinning its nutraceutical properties.

Treballs Finals de Grau d'Enginyeria Informàtica, Facultat de Matemàtiques, Universitat de Barcelona, Any: 2021, Director: Laura Igual Muñoz, [en] Atherosclerosis is one of the main precursors to cardiovascular pathologies, the first defunction cause on developed countries. One of its principal diagnosis methodologies is carotid ultrasound images due to their low cost and intrusivity. Nonetheless, these produce low quality representations, which makes the diagnosis of atherosclerotic plaques a laborious task. In spite of that, other risk measurement methodologies exist. Risk tables which, taking into consideration diverse lifestyle and medical data, assign the probability of an individual to suffer a cardiovascular event. These types of tables inherit their functionality from the Framingham study, which analyzed data of United States population to create its risk function, thus being the first study to do so. However, adapting these tables to all population is not precise, as there are different epidemiological factors that can affect the values of the tables, and conducting studies to adjust them is expensive. Moreover, other limitations exist, as it has been proved that most of the future cardiovascular events end up classified on mid-range risk groups, thus not being medicated, besides an age limit to apply the tables, and not accepting missing values. This project sets out to improve the current REGICOR risk function, computed in catalan population, using machine learning prediction models and a combination of medical and ultrasound data of volunteers.

Background: Greater red and processed meat consumption has been linked to adverse cardiovascular outcomes. However, the impact of these exposures on cardiovascular magnetic resonance (CMR) phenotypes has not been adequately studied.Objective: We describe novel associations of meat intake with cardiovascular phenotypes and investigate underlying mechanisms through consideration of a range of covariates.Design: We studied 19,408 UK Biobank participants with CMR data available. Average daily red and processed meat consumption was determined through food frequency questionnaires and expressed as a continuous variable. Oily fish was studied as a comparator, previously associated with favourable cardiac outcomes. We considered associations with conventional CMR indices (ventricular volumes, ejection fraction, stroke volume, left ventricular mass), novel CMR radiomics features (shape, first-order, texture), and arterial compliance measures (arterial stiffness index, aortic distensibility). We used multivariable linear regression to investigate relationships between meat intake and cardiovascular phenotypes, adjusting for confounders (age, sex, deprivation, educational level, smoking, alcohol intake, exercise) and potential covariates on the causal pathway (hypertension, hypercholesterolaemia, diabetes, body mass index).Results: Greater red and processed meat consumption was associated with an unhealthy pattern of biventricular remodelling, worse cardiac function, and poorer arterial compliance. In contrast, greater oily fish consumption was associated with a healthier cardiovascular phenotype and better arterial compliance. There was partial attenuation of associations between red meat and conventional CMR indices with addition of covariates potentially on the causal pathway, indicating a possible mechanistic role for these cardiometabolic morbidities. However, other associations were not altered with inclusion of these covariates, suggesting importance of alternative biological mechanisms underlying these relationships. Radiomics analysis provided deeper phenotyping, demonstrating association of the different dietary habits with distinct ventricular geometry and left ventricular myocardial texture patterns.Conclusions: Greater red and processed meat consumption is associated with impaired cardiovascular health, both in terms of markers of arterial disease and of cardiac structure and function. Cardiometabolic morbidities appeared to have a mechanistic role in the associations of red meat with ventricular phenotypes, but less so for other associations suggesting importance of alternative mechanism for these relationships.

Background DNA methylation is associated with atherosclerosis and cardiovascular risk factors. However, little evidence regarding its association with cardiovascular diseases in large studies is currently available. We aimed to assess the association between DNA methylation and cardiovascular events, and to determine both the predictive capacity of the identified loci and the causality of those associations. Methods We defined two strategies: epigenome-wide (EWAS) and candidate-gene association studies. In both strategies, we designed one approach with prevalent cases of coronary heart disease (CHD) and another with incident cases of CHD and cardiovascular disease. We used data from three independent cohorts: the REgistre GIroní del COR (REGICOR) study, the Framingham Offspring Study and the Women’s Health Initiative. We also assessed the association between the identified CpGs and cardiovascular risk factors in the three populations. Then, we developed methylation risk scores to evaluate whether their inclusion in the Framingham risk function improved its predictive capacity. Finally, we performed a Mendelian randomization study to determine the causality of the identified associations. Results We found 17 CpGs related to prevalent CHD and/or incident cardiovascular events, two of them observed using both approaches ( p

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER). Some lipoprotein disorders related to the residual risk of premature cardiovascular disease (PCVD) are not detected by the conventional lipid profile. In this case-control study, the predictive power of PCVD of serum sdLDL-C, measured using a lipoprotein precipitation method, and of the physicochemical properties of serum lipoproteins, analyzed by nuclear magnetic resonance (NMR) techniques, were evaluated. We studied a group of patients with a first PCVD event (n = 125) and a group of control subjects (n = 190). Conventional lipid profile, the size and number of Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipopro-teins (HDL) particles, and the number of particles of their subclasses (large, medium, and small) were measured. Compared to controls, PCVD patients had lower concentrations of all LDL parti-cles, and smaller and larger diameter of LDL and HDL particles, respectively. PCVD patients also showed higher concentrations of small dense LDL-cholesterol (sdLDL), and triglycerides (Tg) in LDL and HDL particles (HDL-Tg), and higher concentrations of large VLDL particles. Multivariate logistic regression showed that sdLDL-C, HDL-Tg, and large concentrations of LDL particles were the most powerful predictors of PCVD. A strong relationship was observed between increased HDL-Tg concentrations and PCVD. This study demonstrates that beyond the conventional lipid profile, PCVD patients have other atherogenic lipoprotein alterations that are detected by magnetic resonance imaging (MRI) analysis.

Older age and cardiovascular comorbidities are well-known risk factors for all-cause mortality in patients with coronavirus disease 2019 (COVID-19). Hypertension and age are the 2 principal determinants of arterial stiffness (AS). This study aimed to estimate AS in patients with COVID-19 requiring hospitalization and analyze its association with all-cause in-hospital mortality. This observational, retrospective, multicenter cohort study analyzed 12 170 patients admitted to 150 Spanish centers included in the SEMI-COVID-19 Network. We compared AS, defined as pulse pressure ≥60 mm Hg, and clinical characteristics between survivors and nonsurvivors. Mean age was 67.5 (±16.1) years and 42.5% were women. Overall, 2606 (21.4%) subjects died. Admission systolic blood pressure (BP) P P =0.0001; ORadj: 1.48, P =0.0001, respectively) after adjusting for sex (males, ORadj: 1.6, P =0.0001), age tertiles (second and third tertiles, ORadj: 2.0 and 4.7, P =0.0001), Charlson Comorbidity Index (second and third tertiles, ORadj: 4.8 and 8.6, P =0.0001), heart failure, and previous and in-hospital antihypertensive treatment. Our data show that AS and admission systolic BP