Consensus on lipoprotein(a) of the Spanish Society of Arteriosclerosis. Literature review and recommendations for clinical practice. / Consenso sobre lipoproteína (a) de la Sociedad Española de Arteriosclerosis. Revisión bibliográfica y recomendaciones para la práctica clínica.

The irruption of lipoprotein(a) (Lp(a)) in the study of cardiovascular risk factors is perhaps, together with the discovery and use of proprotein convertase subtilisin/kexin type 9 (iPCSK9) inhibitor drugs, the greatest novelty in the field for decades. Lp(a) concentration (especially very high levels) has an undeniable association with certain cardiovascular complications, such as atherosclerotic vascular disease (AVD) and aortic stenosis. However, there are several current limitations to both establishing epidemiological associations and specific pharmacological treatment. Firstly, the measurement of Lp(a) is highly dependent on the test used, mainly because of the characteristics of the molecule. Secondly, Lp(a) concentration is more than 80% genetically determined, so that, unlike other cardiovascular risk factors, it cannot be regulated by lifestyle changes. Finally, although there are many promising clinical trials with specific drugs to reduce Lp(a), currently only iPCSK9 (limited for use because of its cost) significantly reduces Lp(a). However, and in line with other scientific societies, the SEA considers that, with the aim of increasing knowledge about the contribution of Lp(a) to cardiovascular risk, it is relevant to produce a document containing the current status of the subject, recommendations for the control of global cardiovascular risk in people with elevated Lp(a) and recommendations on the therapeutic approach to patients with elevated Lp(a).

SEA 2024 Standards for Global Control of Vascular Risk. / Estándares de la Sociedad Española de Arteriosclerosis 2024 para el control global del riesgo vascular.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to the knowledge, prevention and treatment of vascular diseases, which are the leading cause of death in Spain and entail a high degree of disability and health expenditure. Atherosclerosis is a multifactorial disease and its prevention requires a global approach that takes into account the associated risk factors. This document summarises the current evidence and includes recommendations for patients with established vascular disease or at high vascular risk: it reviews the symptoms and signs to evaluate, the laboratory and imaging procedures to request routinely or in special situations, and includes the estimation of vascular risk, diagnostic criteria for entities that are vascular risk factors, and general and specific recommendations for their treatment. Finally, it presents aspects that are not usually referenced in the literature, such as the organisation of a vascular risk consultation.

Patients who suffer a first atherosclerotic cardiovascular event while taking statins are often far off of lipid targets.

BACKGROUND AND AIMS: Despite considerable evidence that lipid-lowering therapies (LLTs) afford clinical benefit, the control of low-density lipoprotein cholesterol (LDL-C) is suboptimal, and available LLTs are underused, especially in patients at high and very high cardiovascular (CV) risk. This study assesses the real-world LDL-C target attainment rate in patients on LLT before experiencing a first major acute cardiovascular event (MACE). METHODS AND RESULTS: The HEARTBEAT was a retrospective, multicentre observational study. From March to June 2021 a total of 334 patients on LLT who had a first MACE while being on statins were included in the study. Of these patients, 83.2 % had a high (40.7 %) or very high CV risk (29.0 %) prior to MACE. Overall, 87.5 % and 89.7 % of the patients at high and very high CV risk, respectively, failed to reach the LDL-C target. Regarding LLTs, only 11.8 % and 19.6 % of the patients at high and very high risk had received high-intensity LLTs prior to MACE. It was estimated that if these patients had reached their recommended LDL-C targets, the risk of MACE may have been reduced by a median of 24.5 % and 23.2 % in patients at high and very high risk respectively. CONCLUSIONS: Patients who suffer a first MACE while on statin therapy often were at high/very high CV risk. Despite their risk, LDL-levels and being on statins they are undertreated, and too far from lipid targets. A proper use of high-intensity LLTs led to an increase attainment of LDL targets and lower CV events.

Association between Nordic and Mediterranean diets with lipoprotein phenotype assessed by 1HNMR in children with familial hypercholesterolemia.

BACKGROUND AND AIMS: Both Nordic and Mediterranean diets are considered healthy despite notable regional differences. Although these dietary patterns may lower cardiovascular risk, it is unclear if they improve the lipoprotein phenotype in children with familial hypercholesterolemia (FH). The aim is to determine the impact of Nordic and Mediterranean diets on the advanced lipoprotein profile in children with heterozygous FH (HeFH). METHODS: This was a cross-sectional study performed in children with FH recruited from the Lipid Clinics at Sant Joan University Hospital in Reus (Spain) and Oslo University Hospital (Norway). Two-hundred fifty-six children (mean age 10 y/o; 48% girls): 85 Spanish and 29 Norwegian FH children, and 142 non-FH healthy controls (119 from Spain and 23 from Norway) were included in the study. A pathogenic FH-associated genetic variant was present in 81% of Spanish children with FH and all Norwegian children with FH. An 1H NMR based advanced lipoprotein test (Nightingale®) providing information on the particle number, size and lipid composition of 14 lipoprotein subclasses was performed and correlated to the dietary components. RESULTS: Levels of LDL-C, HDL-C and triglycerides were not significantly different between the Nordic and Mediterranean FH groups. Spanish children with FH had more LDL particles, mainly of the large and medium LDL subclasses, than Norwegian FH children. Spanish FH children also had more HDL particles, mainly medium and small, than Norwegian FH children. The mean LDL size of Spanish FH children was larger, while the HDL size was smaller than that of the Norwegian FH children. The HDL particle number and size were the main determinants of differences between the two groups. In Norwegian children with FH, dietary total fat and MUFAs showed a significant correlation with all apolipoprotein B-containing lipoproteins and LDL size, whereas there was no correlation to SFA. A weaker association pattern was observed in the Spanish children. CONCLUSIONS: The lipoprotein profiles of Spanish and Norwegian children showed differences when studied by 1H NMR. These differences were in part associated with differences in dietary patterns.

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance.

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy-both pharmacologic intervention and lipoprotein apheresis (LA)-is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.

Pregnancy homocysteine and cobalamin status predict childhood metabolic health in the offspring.

BACKGROUND: Inadequate pregnancy cobalamin status has been associated with adverse offspring metabolic health in Indian and Nepalese studies. Studies of pregnancy cobalamin status and mid-childhood health outside of Asia are scarce. METHODS: Associations between pregnancy fasting plasma total homocysteine (tHcy), cobalamin status (plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA)) and mid-childhood metabolic score (MetSco) ((including fat mass index (zFMI), homeostatic model assessment of insulin resistance (zHOMA-IR) and dyslipidemia (zTG - zHDLc)/2) z-scores)) were investigated in a prospective study of 293 mother-child dyads. RESULTS: Highest versus low-mid pregnancy tHcy tertile was associated with higher mid-childhood MetSco, specifically with higher child zFMI. Stratifying by sex, the maternal tHcy-child MetSco association was limited to boys and confirmed for zFMI and zHOMA-IR. The maternal tHcy-child zFMI association was not mediated by birth weight z-score. First trimester plasma cobalamin was not associated with child outcomes, but other indicators of cobalamin status were. Lowest versus mid-high plasma holoTC tertile was associated with MetSco (specifically zFMI and zHOMA-IR) and highest versus low-mid plasma MMA tertile with higher MetSco and dyslipidemia in boys. CONCLUSIONS: Moderately elevated pregnancy tHcy and low cobalamin status were associated with mid-childhood metabolic score in boys. The pregnancy tHcy-child zFMI association was not mediated by birth weight. IMPACT: Fasting plasma total homocysteine (tHcy) during pregnancy and low cobalamin status during early pregnancy are associated with mid-childhood metabolic score and its components in the offspring. These findings were only significant in male offspring. The study provides new evidence that impaired one carbon metabolism during pregnancy is associated with negative health outcomes in the offspring, in a population with low prevalence of cobalamin deficiency. The maternal-offspring associations were observed in the functional markers of cobalamin status (holotranscobalamin and methylmalonic acid) and tHcy, not with plasma cobalamin concentration. Screening for low pregnancy cobalamin status should be considered.

Implications of ACC/AHA Versus ESC/EAS LDL-C Recommendations for Residual Risk Reduction in ASCVD: A Simulation Study From DA VINCI.

PURPOSE: Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (< 70 vs. < 55 mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated. METHODS: DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy (LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C ≥ 70 mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of < 70 or < 55 mg/dl (LDL-C of 69 or 54 mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs and ARRs) were simulated. RESULTS: Of the 2039 patients, 61% did not achieve LDL-C < 70 mg/dl. For patients with LDL-C ≥ 70 mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54 mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively. CONCLUSION: In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10 years versus the ACC/AHA approach.

The CNIC-Polypill reduces recurrent major cardiovascular events in real-life secondary prevention patients in Spain: The NEPTUNO study.

BACKGROUND: To evaluate the effectiveness of a cardiovascular polypill including aspirin, ramipril and atorvastatin (CNIC-Polypill), on the incidence of recurrent major cardiovascular events (MACE) and risk factor control in patients with established atherosclerotic cardiovascular disease (ASCVD) vs different pharmacological therapeutic strategies. METHODS: Retrospective, observational study using data from electronic-health records. Patients were distributed into 4 different cohorts: CNIC-Polypill (case cohort) vs 3 control cohorts: same monocomponents taken separately (Monocomponents), equipotent drugs (Equipotent) and other drugs not included in the previous cohorts (Other therapies). Patients were followed for 2 years or until MACE or death. RESULTS: After propensity score matching, a total of 6456 patients (1614 patients per cohort) were analysed. After 2 years, the risk of recurrent MACE was lower in the CNIC-Polypill cohort compared to the control groups (22%; p = 0.017, 25%; p = 0.002, 27%; p = 0.001, higher in the Monocomponents, Equipotent and Other therapies cohorts, respectively). The incremental proportion of patients who achieved blood pressure (BP) and low-density lipoprotein cholesterol (LDLc) control from baseline was higher in the CNIC-Polypill cohort vs control cohorts (BP controlled patients: +12.5% vs + 6.3%; p < 0.05, +2.2%; p < 0.01, +2.4%; p < 0.01, LDLc controlled patients: +10.3% vs + 4.9%; p < 0.001, +5.7%; p < 0.001, +4.9%; p < 0.001, respectively). Medication persistence was higher in patients treated with the CNIC-Polypill (72.1% vs 62.2%, 60.0% and 54.2%, respectively; p < 0.001) at study end. CONCLUSIONS: In secondary prevention patients, compared with control groups, treatment with the CNIC-Polypill was associated with significant reductions in the accumulated incidence of recurrent MACE, improved BP and LDLc control rates, and increased medication persistence.

Estándares SEA 2022 para el control global del riesgo cardiovascular / SEA 2022 Standards for Global Control of Cardiovascular Risk

La Sociedad Española de Arteriosclerosis tiene entre sus objetivos contribuir al mayor y mejor conocimiento de la enfermedad vascular, su prevención y su tratamiento. Es de sobra conocido que las enfermedades cardiovasculares son la primera causa de muerte en nuestro país y conllevan además un elevado grado de discapacidad y gasto sanitario. La arteriosclerosis es una enfermedad de causa multifactorial y es por ello que su prevención exige un abordaje global que contemple los distintos factores de riesgo con los que se asocia. Así, este documento resume el nivel actual de conocimientos e incluye recomendaciones y procedimientos a seguir ante el paciente que presenta enfermedad cardiovascular establecida o se encuentra con elevado riesgo vascular. En concreto, este documento revisa los principales síntomas y signos a evaluar durante la visita clínica, los procedimientos de laboratorio y de imagen a solicitar de forma rutinaria o aquellos en situaciones especiales. Igualmente, incluye la estimación del riesgo vascular, los criterios diagnósticos de las distintas entidades que son factores de riesgo cardiovascular, plantea recomendaciones generales y específicas para el tratamiento de los distintos factores de riesgo cardiovascular y sus objetivos finales. Por último, el documento recoge aspectos habitualmente poco referenciados en la literatura como son la organización de una consulta de riesgo vascular. (AU)

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to better knowledge of vascular disease, its prevention and treatment. It is well known that cardiovascular diseases are the leading cause of death in our country and entail a high degree of disability and health care costs. Arteriosclerosis is a multifactorial disease and therefore its prevention requires a global approach that takes into account the different risk factors with which it is associated. Therefore, this document summarizes the current level of knowledge and includes recommendations and procedures to be followed in patients with established cardiovascular disease or at high vascular risk. Specifically, this document reviews the main symptoms and signs to be evaluated during the clinical visit, the laboratory and imaging procedures to be routinely requested or requested for those in special situations. It also includes vascular risk estimation, the diagnostic criteria of the different entities that are cardiovascular risk factors, and makes general and specific recommendations for the treatment of the different cardiovascular risk factors and their final objectives. Finally, the document includes aspects that are not usually referenced in the literature, such as the organization of a vascular risk consultation. (AU)

SEA 2022 Standards for Global Control of Cardiovascular Risk. / Estándares SEA 2022 para el control global del riesgo cardiovascular.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to better knowledge of vascular disease, its prevention and treatment. It is well known that cardiovascular diseases are the leading cause of death in our country and entail a high degree of disability and health care costs. Arteriosclerosis is a multifactorial disease and therefore its prevention requires a global approach that takes into account the different risk factors with which it is associated. Therefore, this document summarizes the current level of knowledge and includes recommendations and procedures to be followed in patients with established cardiovascular disease or at high vascular risk. Specifically, this document reviews the main symptoms and signs to be evaluated during the clinical visit, the laboratory and imaging procedures to be routinely requested or requested for those in special situations. It also includes vascular risk estimation, the diagnostic criteria of the different entities that are cardiovascular risk factors, and makes general and specific recommendations for the treatment of the different cardiovascular risk factors and their final objectives. Finally, the document includes aspects that are not usually referenced in the literature, such as the organization of a vascular risk consultation.

Situación en 2020 de los requerimientos para la utilización de inhibidores de PCSK9 en España: resultados de una encuesta nacional / Situation in 2020 of the requirements for the use of PCSK9 inhibitors in Spain: Results of a national survey

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. 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.

AIMS: During 2019 and 2020 a series of meetings over the country were carried out, with the aim of explaining the methodology and criteria for the ellaboration of the recommendations on the use of iPCSK9, published by the Spanish Society of Atherosclerosis (SEA in Spanish). At the end of the meetings, a survey was conducted among the participants, in order to describe the prescription requirements of these drugs in the Spanish regions. METHODOLOGY: Butterfly Project was developed by a scientific Committee of experts in lipids. After the ellaboration of the materials for the project, a train the trainers program was carried out, imparted by 17 experts who were the Project coordinators. Later, 16 regional workshops were performed, with the attendance of 169 medical doctors involved in the management of hipercolesterolemia. The attendants responded the survey, where they were asked different questions on the use of iPCSK9 on their clinical practice. RESULTS: A high heterogeneity among centers regarding the requirements and difficulties for iPCSK9 prescription was revealed. Twenty one per cent of responders indicated to have low difficulties to prescribe iPCSK9 in their hospitals, whereas 78% found moderate or high difficulties. The difficulties came from burocracy- administrative aspects (18%), restrictions in the indication (41%) and both (38%). In general, the obstacles did not depend on the hospital level, neither the speciality, or the presence of lipid units, although the existance of lipid units was associated with a higher number of patients treated with iPCSK9. The factors which were associated with higher difficulty in the prescription were: the presence of an approval committee in the hospitals, the frequency in the revision of the treatment by hospital pharmacy, the temporal cadence of the prescription, the profile of patients seen and the criteria followed by the specialists for the prescription.

Situation in 2020 of the requirements for the use of PCSK9 inhibitors in Spain: Results of a national survey. / Situación en 2020 de los requerimientos para la utilización de inhibidores de PCSK9 en España: resultados de una encuesta nacional.

AIMS: During 2019 and 2020 a series of meetings over the country were carried out, with the aim of explaining the methodology and criteria for the ellaboration of the recommendations on the use of iPCSK9, published by the Spanish Society of Atherosclerosis (SEA in Spanish). At the end of the meetings, a survey was conducted among the participants, in order to describe the prescription requirements of these drugs in the Spanish regions. METHODOLOGY: Butterfly Project was developed by a scientific Committee of experts in lipids. After the ellaboration of the materials for the project, a train the trainers program was carried out, imparted by 17 experts who were the Project coordinators. Later, 16 regional workshops were performed, with the attendance of 169 medical doctors involved in the management of hipercolesterolemia. The attendants responded the survey, where they were asked different questions on the use of iPCSK9 on their clinical practice. RESULTS: A high heterogeneity among centers regarding the requirements and difficulties for iPCSK9 prescription was revealed. Twenty one per cent of responders indicated to have low difficulties to prescribe iPCSK9 in their hospitals, whereas 78% found moderate or high difficulties. The difficulties came from burocracy- administrative aspects (18%), restrictions in the indication (41%) and both (38%). In general, the obstacles did not depend on the hospital level, neither the speciality, or the presence of lipid units, although the existance of lipid units was associated with a higher number of patients treated with iPCSK9. The factors which were associated with higher difficulty in the prescription were: the presence of an approval committee in the hospitals, the frequency in the revision of the treatment by hospital pharmacy, the temporal cadence of the prescription, the profile of patients seen and the criteria followed by the specialists for the prescription. CONCLUSION: The results show important diferences in the treatment with iPCSK9 in the context of clinical practice in Spain. The analysis of these results will permit to make proposals regarding future actions addressed to reach the equity in the access to iPCSK9 in Spain, with the main aim of maximizing their potential benefit according to the patients profile.

MCF-7 Drug Resistant Cell Lines Switch Their Lipid Metabolism to Triple Negative Breast Cancer Signature.

Obesity and adipose tissue have been closely related to a poor cancer prognosis, especially in prostate and breast cancer patients. The ability of transferring lipids from the adipose tissue to the tumor cells is actively linked to tumor progression. However, different types of breast tumor seem to use these lipids in different ways and metabolize them in different pathways. In this study we have tracked by mass spectrometry how palmitic acid from the adipocytes is released to media being later incorporated in different breast cancer cell lines (MDA-MB-231, SKBR3, BT474, MCF-7 and its resistant MCF-7 EPIR and MCF-7 TAXR). We have observed that different lines metabolize the palmitic acid in a different way and use their carbons in the synthesis of different new lipid families. Furthermore, we have observed that the lipid synthesis pattern varied according to the cell line. Surprisingly, the metabolic pattern of the resistant cells was more related to the TNBC cell line compared to their sensitive cell line MCF-7. These results allow us to determine a specific lipid pattern in different cell lines that later might be used in breast cancer diagnosis and to find a better treatment according to the cancer molecular type.

Altered Serum Metabolic Profile Assessed by Advanced 1H-NMR in Breast Cancer Patients.

BACKGROUND: Altered lipid metabolism has been described in some types of cancer. To analyse in depth the metabolic modifications in breast cancer patients, advanced 1H-nuclear magnetic resonance was performed in these patients. The main objective of this paper was to define a specific lipidomic signature for these cancer patients. MATERIALS AND METHODS: Serum from 240 women (171 breast cancer patients and 69 control women) were studied and analysed by nuclear magnetic resonance. RESULTS: Triglyceride-enriched particles, specifically very low-density lipoprotein triglycerides, intermediate-density lipoprotein triglycerides, low-density lipoprotein triglycerides, and high-density lipoprotein triglycerides, were positively associated with breast cancer. Moreover, alanine, tyrosine, and branched amino acids were also associated with increased risk of breast cancer. CONCLUSIONS: Breast cancer patients showed a modified metabolome, giving a very interesting tool to draw different radar charts between control women and breast cancer patients. To our knowledge, this is the first time that advanced nuclear magnetic resonance profiling has been used to identify relevant and specifically altered lipid or amino acid metabolites in BC serum samples. The altered metabolic signature could be analysed for early and reliable BC patient diagnosis and prognosis.

Plasma expression of microRNA-425-5p and microRNA-451a as biomarkers of cardiovascular disease in rheumatoid arthritis patients.

To validate in a cohort of 214 rheumatoid arthritis patients a panel of 10 plasmatic microRNAs, which we previously identified and that can facilitate earlier diagnosis of cardiovascular disease in rheumatoid arthritis patients. We identified 10 plasma miRs that were downregulated in male rheumatoid arthritis patients and in patients with acute myocardial infarction compared to controls suggesting that these microRNAs could be epigenetic biomarkers for cardiovascular disease in rheumatoid arthritis patients. Six of those microRNAs were validated in independent plasma samples from 214 rheumatoid arthritis patients and levels of expression were associated with surrogate markers of cardiovascular disease (carotid intima-media thickness, plaque formation, pulse wave velocity and distensibility) and with prior cardiovascular disease. Multivariate analyses adjusted for traditional confounders and treatments showed that decreased expression of microRNA-425-5p in men and decreased expression of microRNA-451 in women were significantly associated with increased (ß = 0.072; p = 0.017) and decreased carotid intima-media thickness (ß = -0.05; p = 0.013), respectively. MicroRNA-425-5p and microRNA-451 also increased the accuracy to discriminate patients with pathological carotid intima-media thickness by 1.8% (p = 0.036) in men and 3.5% (p = 0.027) in women, respectively. In addition, microRNA-425-5p increased the accuracy to discriminate male patients with prior cardiovascular disease by 3% (p = 0.008). Additionally, decreased expression of microRNA-451 was significantly associated with decreased pulse wave velocity (ß = -0.72; p = 0.035) in overall rheumatoid arthritis population. Distensibility showed no significant association with expression levels of the microRNAs studied. We provide evidence of a possible role of microRNA-425-5p and microRNA-451 as useful epigenetic biomarkers to assess cardiovascular disease risk in patients with rheumatoid arthritis.

El rastreo masivo de datos es una segunda oportunidad para mejorar el manejo de los pacientes con fenotipo de hipercolesterolemia familiar / Massive data screening is a second opportunity to improve the management of patients with familial hypercholesterolemia phenotype

Introducción: La Hipercolesterolemia Familiar (HF) es una enfermedad autósómica dominante con una prevalencia estimada entre 1/200-250. Se encuentra infra-tratada e infra-diagnosticada. El rastreo masivo de datos puede incrementar la detección de pacientes con HF. Métodos: Población a estudio: Residentes en la zona sanitaria de cobertura (N: 195.000 habitantes) y con al menos una determinación de colesterol ligado a lipoproteínas de baja densidad (C-LDL) realizada entre el 1 de Enero de 2010 y el 30 de Diciembre de 2019. Se seleccionaron los valores más altos de C-LDL. Criterios de exclusión: síndrome nefrótico, hipotiroidismo, tratamiento hipotiroideo o triglicéridos > 400 mg/dL. Se analizaron 7 algoritmos sugestivos de fenotipo de Hipercolesterolemia Familiar (F-HF).Se seleccionó el algoritmo más eficaz y de fácil traslación a la práctica clínica. Resultados: Partiendo de 6.264.877 asistencias y 288.475 pacientes tras aplicar los criterios de inclusión-exclusión se incluyeron 504.316 analíticas correspondiendo a 106.382 adultos y 10.509 < 18 años. El algoritmo seleccionado presentó una prevalencia de 0.62%.Se detectaron 840 pacientes con fenotipo de Hipercolestereolemia Familiar (F-HF) siendo el 55.8% mujeres y 178 <18 años, El 9.3% tenían antecedentes de enfermedad cardio-vascular (ECV) y 16.4% habían fallecido. El 65% de los pacientes en prevención primaria presentaron valores de C-LDL >130 mg/dL y el 83% en prevención secundaria valores >70mg/dL. Se obtuvo una ratio de 7.64 (1-18) pacientes con HF-P por médico solicitante de analítica.Conclusiones: El rastreo masivo de datos y el perfilado de pacientes son herramientas eficaces y fácilmente aplicables en práctica clínica para la detección de pacientes con HF.(AU)

Introduction: Familial Hypercholesterolemia (FH) is an autosomal dominant disease with an estimated prevalence between 1/200-250. It is under-treated and underdiagnosed. Massive data screening can increase the detection of patients with FH. Methods: Study population: Residents in the health coverage area (N: 195.000 inhabitants) and with at least one determination of cholesterol linked to low-density lipoproteins (LDL-C) carried out between January 1, 2010 and December 30, 2019. The highest LDL-C values were selected. Exclusion criteria: nephrotic syndrome, hypothyroidism, Hypothyroid treatment or triglycerides> 400 mg / dL. Seven algorithms suggestive of Familial Hypercholesterolemia Phenotype (HF-P) were analyzed, selecting the most efficient algorithm that could easily be translated into clinical practice. Results: Based on 6.264.877 assistances and 288.475 patients, after applying the inclusion-exclusion criteria, 504.316 tests were included, corresponding to 106.382 adults and 10.509 <18 years. The selected algorithm presented a prevalence of 0.62%. 840 patients with HF-P were detected, 55.8% being women and 178 <18 years old, 9.3% had a history of cardiovascular disease (CVD) and 16.4% had died. 65% of the patients in primary prevention had LDL-C values> 130 mg / dL and 83% in secondary prevention values> 70mg / dL. A ratio of 7.64 (1-18) patients with HF-P per analytical requesting physician was obtained. Conclusions. Massive data screening and patient profiling are effective tools and easily applicable in clinical practice for the detection of patients with FH.

Intensive low-density lipoprotein cholesterol lowering in cardiovascular disease prevention: opportunities and challenges.

Elevated levels of low-density lipoprotein cholesterol (LDL-C) are associated with increased risk of coronary heart disease and stroke. Guidelines for the management of dyslipidaemia from the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) were updated in late 2019 in light of recent intervention trials involving the use of innovative lipid-lowering agents in combination with statins. The new guidelines advocate achieving very low LDL-C levels in individuals at highest risk, within the paradigm of 'lower is better'. With the advent of combination therapy using ezetimibe and/or proprotein convertase subtilisin/kexin type 9 inhibitors in addition to statins, the routine attainment of extremely low LDL-C levels in the clinic has become a reality. Moreover, clinical trials in this setting have shown that, over the 5-7 years of treatment experience to date, profound LDL-C lowering leads to further reduction in cardiovascular events compared with more moderate lipid lowering, with no associated safety concerns. These reassuring findings are bolstered by genetic studies showing lifelong very low LDL-C levels (<1.4 mmol/L; <55 mg/dL) are associated with lower cardiovascular risk than in the general population, with no known detrimental health effects. Nevertheless, long-term safety studies are required to consolidate the present evidence base. This review summarises key data supporting the ESC/EAS recommendation to reduce markedly LDL-C levels, with aggressive goals for LDL-C in patients at highest risk, and provides expert opinion on its significance for clinical practice.

Practical guidance for combination lipid-modifying therapy in high- and very-high-risk patients: A statement from a European Atherosclerosis Society Task Force.

BACKGROUND AND AIMS: This European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in high-risk and very-high-risk patients. METHODS: Evidence-based review. RESULTS: Statin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-high-risk patients with mild to moderately elevated TG levels (>2.3 and < 5.6 mmol/L [>200 and < 500 mg/dL) on a statin, treatment with either a fibrate or high-dose omega-3 fatty acids (icosapent ethyl) may be considered, weighing the benefit versus risks. Combination with fenofibrate may be considered for both macro- and microvascular benefits in patients with type 2 diabetes mellitus. CONCLUSIONS: This guidance aims to improve real-world use of guideline-recommended combination lipid modifying treatment.