Effectiveness and safety of alirocumab and evolocumab for hypercholesterolemia in a population with high cardiovascular risk.

BACKGROUND AND AIMS: The criteria for the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) more restrictive than those approved were established in Catalonia by the Health System (CatSalut) to improve their efficiency, with different LDL-C values from which to start treatment according to risk factors. The aim of the study is to analyse adherence to these criteria and results. METHODS: A retrospective study of patients treated with PCSK9i at Vall d'Hebron University Hospital between 2016 and 2021 was performed using data from the Registry of Patients and Treatments and medical records. The degree of agreement with the CatSalut criteria, LDL-C-responders (decrease ≥30%), cardiovascular events and discontinuations were analysed. RESULTS: A total of 193 patients treated with PCSK9i were followed for a median of 27 months (IQR 23). The median age was 61 (IQR 15); 62.7% were men. Seventy percent of the patients had non-familial hypercholesterolemia. Treatment was for secondary prevention of cardiovascular disease in 82.4% of cases. The median LDL-C decreased from 139 (IQR 52) to 59 (IQR 45) mg/dL. The percentage of LDL-C reduction was 61.0% (IQR 30). In 72.5% of patients, all CatSalut criteria for starting treatment were met. The rate of responders was 85.4%. During follow-up, 19 patients (9.8%) had a cardiovascular event, and 15 (7.7%) discontinued treatment, in two cases due to toxicity. CONCLUSION: PCSK9i were used according to CatSalut criteria in three out of four cases. In this high-risk population, incidence of cardiovascular events was similar to that in clinical trials.

Medium/long term evaluation of lipid profile after bariatric surgery (gastric bypass versus sleeve gastrectomy).

INTRODUCTION: Bariatric surgery aims to reduce weight and resolve the comorbidities associated with obesity. Few studies have assessed mid/long-term changes in lipid profile with sleeve gastrectomy versus gastric bypass. This study was conducted to assess and compare changes in lipid profile with each procedure after 60 months. METHODS: This was an observational, retrospective study of analytical cohorts enrolling 100 patients distributed into two groups: 50 had undergone gastric bypass (GBP) surgery and 50 sleeve gastrectomy (SG) surgery. Total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured before surgery and at 1, 6, 12, 24, 36, 48, and 60 months. Weight loss and the resolution of dyslipidemia with each of the procedures were also assessed. RESULTS: Ninety-five of the 100 patients completed follow-up. At 60 months, TC and LDL levels had significantly decreased in the BPG group (167.42 ±â€¯31.22 mg/dl and 88.06 ±â€¯31.37 mg/dl, respectively), while there were no differences in the SG group. Increased HDL levels were seen with both procedures (BPG: 62.69 ±â€¯16.3 mg/dl vs. SG: 60.64 ±â€¯18.73 mg/dl), with no difference between the procedures. TG levels decreased in both groups (BPG: 86.06 ±â€¯56.57 mg/dl vs. SG: 111.09 ±â€¯53.08 mg/dl), but values were higher in the BPG group (P < .05). The percentage of overweight lost (PSP) was higher in the BPG group: 75.65 ±â€¯22.98 mg/dl vs. the GV group: 57.83 ±â€¯27.95 mg/dl. CONCLUSION: Gastric bypass achieved better mid/long-term results in terms of weight reduction and the resolution of hypercholesterolemia as compared to sleeve gastrectomy. While gastric bypass improved all lipid profile parameters, sleeve gastrectomy only improved HDL and triglyceride levels.

Effect of low-density lipoproteins and trehalose on the quality of cryopreserved bovine semen / Efecto de las lipoproteínas de baja densidad y la trehalosa en la calidad del semen bovino criopreservado / Efeito das lipoproteínas de baixa densidade e trealose na qualidade do sêmen bovino criopreservado

Abstract Background: In artificial insemination, chicken egg yolk is added to bovine semen to protect it during the cryopreservation process, although it contains substances that can affect the microbiological quality and metabolism of sperm. Objective: To evaluate post-thaw quality of bovine cryopreserved semen added with centrifuged and non-centrifuged egg yolk, low-density lipoproteins (LDL), and trehalose (T). Methods: Ten ejaculates from five bulls were cryopreserved under the treatments T1: pure egg yolk (PEY) at 20% v/v, T2: centrifuged egg yolk (CEY) at 20% v/v, T3: LDL at 8% v/v, T4: T at 100 mM, and T5: T at 100 mM plus LDL at 8% v/v (TLDL). Spermatic motility and kinetics, functional membrane integrity (FMI), structural membrane integrity (SMI), sperm vitality (SV) and abnormal morphology (AM) were assessed using the Sperm Class Analyzer (SCA®) system, hypoosmotic test (HOST), SYBR/PI probes, and eosin-nigrosin staining, respectively. A completely randomized design was used. Normal distribution of the variables was validated through the Kolmogórov- Smirnov test. A generalized linear model was used to determine sources of variation. Means were compared using the Tukey test. Results: Inclusion of CEY or LDL had a similar effect on sperm protection, and were superior for motility, kinetics and membrane integrity compared to the other treatments (p<0.05). CEY was superior for progressive motility (p<0.05). The cryoprotective action of LDL was similar to TLDL for motility and kinetics, SMI, SV, and AM (p<0.05). Inclusion of PEY and T resulted in the lowest semen quality (p<0.05). The use of T resulted in a reduction in FMI and SMI (p<0.05). No differences in AM between treatments were found (p>0.05). Conclusions: Egg yolk can be replaced by centrifuged egg yolk or low-density lipoproteins in the freezing extender used for bovine semen used in artificial insemination.

Resumen Antecedentes: la yema de huevo de gallina se agrega al semen bovino usado en inseminación artificial para protegerlo durante el proceso de criopreservación, aunque ésta tiene sustancias que pueden afectar el metabolismo espermatico y la calidad microbiológica del semen. Objetivo: evaluar la calidad post-descongelación del semen bovino criopreservado agregado con yema de huevo centrifugada y no centrifugada, lipoproteínas de baja densidad (LDL) y trehalosa (T). Métodos: diez eyaculados de cinco toros se criopreservaron bajo los tratamientos, T1: yema de huevo pura (PEY) al 20% v/v, T2: yema de huevo centrifugada (CEY) al 20% v/v, T3: LDL al 8% v/v, T4: T a 100 mM, y T5: T a 100 mM más LDL al 8% v/v (TLDL). La movilidad y la cinética espermática, la integridad funcional de la membrana (FMI), la integridad estructural de la membrana (SMI), la vitalidad espermática (SV) y la morfología anormal (AM), se determinaron mediante el sistema Sperm Class Analyzer (SCA®), la prueba hipoosmótica (HOST), las sondas SYBR/PI y la tinción con eosina-nigrosina, respectivamente. Se utilizó un diseño completamente al azar. La normalidad de las variables se validó mediante la prueba de Kolmogórov-Smirnov. Se utilizó un modelo lineal generalizado para determinar las fuentes de variación. Las medias de los tratamientos se compararon mediante la prueba de Tukey. Resultados: CEY y LDL tuvieron un efecto similar en la protección de los espermatozoides, siendo superiores a los demás tratamientos respecto a movilidad, cinética e integridad de la membrana (p<0,05). CEY fue superior para la movilidad progresiva (p<0,05). La acción crioprotectora de LDL fue similar a TLDL para movilidad y cinética, SMI, AM y SV (p<0,05). PEY y T resultaron en la más baja calidad seminal (p<0,05). El uso de T redujo la FMI y la SMI (p<0,05). No se encontraron diferencias en AM entre los tratamientos (p>0,05). Conclusiones: la yema de huevo puede reemplazarse por yema de huevo centrifugada o por lipoproteinas de baja densidad en el diluyente de congelación usado para semen bovino destinado a inseminacion artificial.

Resumo Antecedentes: a gema de ovo de galinha tem sido utilizada com a finalidade de proteger o sêmen bovino durante o processo de criopreservação, embora tenha substâncias que possam afetar o metabolismo dos espermatozóides e a qualidade microbiológica do sêmen utilizado para a inseminação artificial. Objetivo: avaliar a qualidade pós-descongelamento do sêmen bovino criopreservado com gema de ovo centrifugada e não centrifugada, lipoproteínas de baixa densidade (LDL) e trealose (T). Métodos: dez ejaculados de cinco touros foram criopreservados sob os tratamentos, T1: gema de ovo pura (PEY) 20% v/v, T2: gema de ovo centrifugada (CEY) 20% v/v, T3: LDL 8% v/v, T4: T 100 mM e T5: T 100 mM mais LDL 8% v/v (TLDL). Mobilidade e cinética espermática, integridade funcional da membrana (FMI), integridade estrutural da membrana (SMI), vitalidade espermática (SV) e morfologia anormal (AM) foram determinadas por o sistema Sperm Class Analyzer (SCA®), teste hiposmótico (HOST), coloração com SYBR/PI e eosina-nigrosina, respectivamente. Um design completamente aleatoriedade foi usado. A normalidade das variáveis foi validada pelo teste de Kolmogorov-Smirnov. Um modelo linear generalizado foi utilizado para determinar as fontes de variação. As médias dos tratamentos foram comparadas pelo teste de Tukey. Resultados: T2 (CEY) e T3 (LDL) tiveram efeito similar na proteção espermática, sendo superior aos demais tratamentos para mobilidade, cinética e integridade da membrana (p<0,05). T2 (CEY) foi superior para mobilidade progressiva (p<0,05). A ação crioprotetora de T3 (LDL) foi semelhante à T5 (TLDL) para motilidade e cinética, SMI, SV e AM (p<0,05). T1 (PEY) e T4 (T) tiveram a menor qualidade seminal (p<0,05). O uso de T4 (T) produziu uma redução na SMI e FMI (p<0,05). Não foram encontradas diferenças na AM entre os tratamentos (p>0,05). Conclusões: a gema de ovo pode ser substituída por gema de ovo centrifugada ou lipoproteínas de baixa densidade no diluente de congelamento de sêmen bovino.

Bempedoic acid. Mechanism of action and pharmacokinetic and pharmacodynamic properties. / Ácido bempedoico. Mecanismo de acción y propiedades farmacocinéticas y farmacodinámicas.

Bempedoic acid acts by inhibiting adenosine triphosphate-citrate lyase (ACL) and consequently cholesterol biosynthesis, leading to increased expression of LDL receptors and increasing low-density lipoproteins (LDL-C) plasma clearence. It is a prodrug for oral administration with intracellular activation. It is activatedin liver cells and to a lesser extent in kidney cells, being absent in adipose tissue and muscle cells. Therefore, unlike statins, its potential myotoxic effect is very limited. It has recently been approved as a lipid-lowering drug in combination with diet, with statins, or with other lipid-lowering drugs in patients with hypercholesterolaemia, mixed dyslipidaemia, statin intolerance, or when these are contraindicated. The marketing of bempedoic acid implies, in clinical practice, having a new family of lipid-lowering drugs.

Prevalencia de dislipidemias en pacientes obesos / Dylispidemia prevalence in obese patients

Introducción: Las dislipidemias asociadas a la obesidad constituyen factores de riesgo de varias enfermedades especialmente del sistema cardiovascular. Objetivo: Determinar la prevalencia de dislipidemias en pacientes obesos. Métodos: Se realizó un estudio correlacional, retrospectivo y transversal de150 pacientes obesos, quienes acudieron a la consulta externa de la Clínica Medina del Hospital Básico de Guayaquil, desde el 2018 hasta el 2019. Las variables analizadas fueron edad, sexo, índice de masa corporal y resultados de laboratorio, tales como colesterol total, triglicéridos, colesterol LDL y dislipidemia mixta (colesterol HDL y VLDL). Resultados: En la serie predominaron el sexo masculino (62,6%), los pacientes con más de 65 años de edad (42,0 %), los niveles entre rango crítico y alto riesgo (66 pacientes); 16,0 % se clasificaron de alto riesgo con niveles de colesterol superior a 240 mg/dL. Mostraron resultados anormales en cuanto a los triglicéridos 62 afectados, en un rango mayor de 150 con niveles y limítrofe altos. Conclusiones: Se observó una correspondencia entre las dislipidemias y la obesidad, pues todos los pacientes presentaron algún tipo de alteración en los lípidos.

Introduction: Dyslipidemias associated to obesity constitute risk factors of several diseases specially from the cardiovascular system. Objective: To determine the prevalence of dyslipidemias in obese patients Methods: A correlational restrospective and cross-sectional study of 150 obese patients, who visited the outpatients department of Medina Clinic from Hospital Básico in Guayaquil, from 2018 to 2019. Variables used were age, sex, body mass index and laboratory results such as total cholesterol, triglycerids. LDL colesterol and mixed dyslipidemias (cholesterol HDL and VLDL). Results: In the serie, male sex (62.6 %), patients over 65 years (42.0 %), levels between critical and high risk (66 patients) prevailed, 16.0 % were classified as high risk patients with cholesterol level over 240 mg/dL. Sixty two patients showed subnormal results regarding triglycerids, in a rank higher than 150 with high limits and levels. Conclusions: A correspondance between dyslipidemias and obesity was observed, as all patients presented some type of change in lipids.

PCSK9 inhibitors: Ratification of the role of LDL cholesterol in cardiovascular prevention. Towards a convergence of European and North American prevention guidelines? / Inhibidores de PCSK9: ratificación del papel del colesterol LDL en prevención cardiovascular. ¿Hacia la convergencia en las guías de prevención europeas y norteamericanas?

The epidemiological association of cholesterol associated with low density lipoproteins (LDL-c) levels and the development of atherosclerotic vascular disease has been ratified by mendelian randomization studies. Paradoxically, the success of statins led to the underestimation of other lipid-lowering therapies and even the measurement of LDL-c. Recent studies show that the reduction of LDL-c to extraordinarily low levels through absorption inhibition, and, in a particularly intensive manner, with monoclonal antibodies against pro-protein convertase subtilisine Kesine 9 (PCSK9) continues to offer cardiovascular protection. However, the high cost and limited experience with PCSK-9 inhibitors advised a prudent use of them. An appropriate selection of patients most likely to benefit from treatment with PCSK9 inhibitors emerges as the basis for a consensus of international guidelines: the combination of a high absolute vascular risk and a greater expected benefit by the starting LDL-c levels.

Encare clínico de las dislipemias / Clinical care of dyslipidemias / Encargo clínico de dislipidemias

Resumen: El manejo de los pacientes con dislipemias en la práctica clínica diaria implica el conocimiento de la evidencia científica relevante, la experiencia clínica, el sentido común, así como el respeto a la voluntad del paciente. La evidencia demuestra que el tratamiento hipolipemiante con estatinas reduce la morbimortalidad cardiovascular en un amplio grupo de pacientes, con un porcentaje de efectos colaterales bajo. Un punto crítico en el tratamiento es la decisión de iniciar o no dichos fármacos. Hay pacientes que tienen indicación formal de estatinas sin necesidad de hacer una evaluación del riesgo vascular. Tal es el caso de los que están en prevención secundaria, pacientes con colesterol unido a las lipoproteínas de baja densidad (C-LDL) muy alto (>190 mg/dl) y diabéticos entre 40 y 75 años. En los demás individuos la indicación de estatinas pasa en primer lugar por una evaluación formal del riesgo cardiovascular. Con este fin, las guías estadounidenses sugieren el uso de las Pooled Cohort Equations, en tanto que las guías europeas utilizan el Heartscore. Ambos scores estratifican a los pacientes en cuatro grupos según la intensidad del riesgo. El beneficio absoluto en la reducción del riesgo de eventos es tanto mayor cuanto más elevado sea el riesgo basal del paciente. Es por ello que se recomienda que tanto la intensidad del tratamiento, como el nivel de descenso objetivo de C-LDL, sean tanto mayores cuanto mayor sea el riesgo del paciente. Las recomendaciones de ambas guías no son coincidentes en algunos casos. Por lo tanto, además del riesgo cardiovascular se debe considerar el riesgo de efectos adversos potenciales y la voluntad del paciente en una discusión franca con su médico. El ezetimibe primero y los inhibidores PCSK9 después (limitados en estos momentos por costos y disponibilidad) aparecen como los grandes aliados de las estatinas, cuando no se toleran las dosis adecuadas o no se llega al C-LDL objetivo. A los efectos del abordaje del tema hemos optado por analizar cinco historias clínicas representativas de los principales escenarios clínicos que obligan al médico a tomar decisiones terapéuticas específicas.

Summary: In daily clinical practice the management of patients with dyslipidemias implies knowledge of relevant clinical scientific evidence, common sense, as respect of patient preferences. There is strong evidence that treatment of dyslipidemias mainly with statins reduces morbidity and mortality in a wide group of patients with few side effects. A critical step in management of this individuals is to make the decision of whether statin treatment is indicated or not. There are patients that have a clear indication of statin use without any further cardiovascular risk calculation. Such is the case in secondary prevention, patients with extremely high low density lipoprotein cholesterol levels (>190 mg/dl) and diabetics between 40 and 75 years-old. In all other patients, statin indication should start with a formal cardiovascular risk evaluation. American guidelines suggest using the Pooled Cohort Risk Equations and European guidelines prefer Heartscore. Both scoring systems stratify risk in four categories according to risk intensity. The absolute cardiovascular risk reduction obtained with treatment increases in parallel with the basal cardiovascular risk. This explains the recommendation that both treatment intensity and magnitude of low density lipoprotein cholesterol lowering should increase as the risk of the patient increases. Recommendations provided by American and European guidelines do not always coincide. Thus, besides basal cardiovascular risk estimation, potential adverse drug effects and patient preferences should always be considered in the context of a clinician-patient frank discussion. Ezetimibe first and PCSK9 inhibitors eventually (currently limited by costs and availability) appear as the great allies of statins, when adequate doses are not tolerated or the target is not reached. We will tackle the subject through five cases that illustrate the main clinical situations in which physicians have to adopt specific therapeutic decisions.

Resumo: O manejo de pacientes com dislipidemias na prática clínica diária envolve conhecimento de provas científicas relevantes, experiência clínica, senso comum, bem como a respeito da vontade do paciente. A evidência mostra que o tratamento hipolipemiente com estatina reduz a morbimortalidade cardiovascular em um grande grupo de pacientes com uma baixa taxa de efeitos colaterais. Um ponto crítico no tratamento desses pacientes é a decisão de iniciar ou não estas drogas. Há pacientes que têm indicação formal de estatinas sem necessidade de fazer uma avaliação de risco vascular. Tal é o caso dos pacientes que estão na prevenção secundária, pacientes com colesterol da lipoproteína de baixa densidade muito alta (>190 mg/dl) e diabéticos entre 40 e 75 anos. Em outros indivíduos a indicação de uma estatinas passa primeiro através de uma avaliação formal de risco cardiovascular. Para este fim diretrizes Americanas sugerem o uso do Pooled Cohort Equations, enquanto as directrizes europeias usam o Heartscore. Ambos scores estratificam pacientes em quatro grupos de acordo com a intensidade do risco. O benefício absoluto na redução do risco de eventos é maior quanto mais elevado seja o risco base do paciente. Por isso, recomenda-se que tanto a intensidade do tratamento e do nível de descida desejada da lipoproteína de baixa densidade, são muito maior quanto maior for o risco do paciente. As recomendações de ambas as guias em alguns casos não são coincidentes. Portanto, além do risco cardiovascular deve ser considerado o risco de efeitos adversos potenciais e a vontade do paciente em uma discussão franca entre médico e paciente. Ezetimiba primeiro e os inibidores PCSK9 depois (limitado atualmente pela disponibilidade e custo) aparecem como os grandes aliados das estatinas, quando não são toleradas doses adequadas ou não se chega ao objetivo. Para efeitos da abordagem do assunto que escolhemos para analisar cinco histórias clínicas de pacientes representativos dos principais cenários clínicos que exige do médico a tomar decisões terapêuticas específicas.

Indications of PCSK9 inhibitors in clinical practice. Recommendations of the Spanish Sociey of Arteriosclerosis (SEA), 2019. / Indicaciones de los inhibidores de PCSK9 en la práctica clínica. Recomendaciones de la Sociedad Española de Arteriosclerosis (SEA), 2019.

A group of experts convened by the Spanish Society of Arteriosclerosis (SEA) has been in charge of updating the SEA document on the indications of PCSK9 inhibitors (PCSK9i) in clinical practice that was published in 2016. This update is justified by the fact that the data from clinical trials carried out on a large scale with PCSK9i have shown that in addition to their high potency to lower atherogenic cholesterol, they reduce the risk of atherosclerotic cardiovascular disease, both in patients with stable disease, and with recent disease, and with a high degree of security. This update provides the recommendations and level of evidence for the prescription of iPCSK9 in patients with homozygous and heterozygous familial hypercholesterolemia, with atherosclerotic cardiovascular disease, and in primary prevention in patients with very high cardiovascular risk. These recommendations have been established taking into account the concentration of LDL-C, the clinical situation of the patient, the additional risk factors and the cost-effectiveness of their use.

Fibra y capacidad antioxidante de algas comestibles en ratas suficientes o deficientes en vitamina E / Fiber and antioxidant capacity of edible algae in vitamin E sufficient and deficient rats / Fibra e capacidade antioxidante de algas comestíveis em camundongos suficientes e deficientes em vitamina E

Debido a la importancia que han alcanzado las algas en la alimentación de los países occidentales aquí se estudió el potencial de las algas Nori y Wakame como fuentes de fibra y capacidad antioxidante en ratas en crecimiento alimentadas con dietas suficientes o deficientes en vitamina E (vit E) durante 15 días. Hubo 3 grupos de ratas que recibieron dietas: 1. grupo control, 2. grupo Nori y 3 grupo Wakame con vit E y 3 grupos similares sin vit E. En las dietas con vit E, Nori produjo una reducción de crecimiento y las dos algas causaron una acumulación de vit E hepática, una reducción en la vit E plasmática y un aumento en TBARS en plasma e hígado. En contraste, cuando las algas se ofrecieron en dietas exentas de vit E, el grupo Nori recuperó su capacidad de crecer, mantuvo una mayor reserva de vit E en el hígado que el grupo control deficiente en vit E y el consumo de ambas algas resultó en TBARS plasmáticos por debajo de las ratas controles deficientes en vit E, lo que señaló que las algas se comportaron mejor en dietas sin vit E. Adicionalmente, se observó que las algas estimularon la función excretora del intestino sin afectar su capacidad absortiva.

In western countries, edible seaweed consumption has markedly increased in recent years. Accordingly, in this study the antioxidant capacity and fiber value of Nori and Wakame algae were evaluated in growing rats fed with sufficient of deficient vitamin E. There were 3 groups of rats: 1. Control, 2. Nori and 3. Wakame with vitamin E and 3 similar groups without vitamin E. The diet with Nori and sufficient vitamin E caused a reduction in growth and Nori and Wakame were associated with liver vitamin E accumulation, plasma vitamin E reduction and an increase in TBARS in liver and plasma. In contrast, when the same diets were offered without vitamin E, the Nori fed rats recovered their growing capacity, they maintained a higher vitamin E reserve than the control or Wakame fed rats, and the consumption of both algae was associated with lower plasma TBARS than vitamin E deficient rats, indicating that these algae are best accepted when offered without vitamin E. In addition, both algae improved the excretory capacity of the intestine without affecting its absorption function.

Visto que nos países ocidentais revestiu importância o consumo de algas na alimentação, aqui foi estudado o potencial das algas Nori e Wakame como fontes de fibra e capacidade antioxidante em ratos em crescimento, alimentados com dietas suficientes ou deficientes em vitamina E (vit E) durante 15 dias. Houve 3 grupos de ratos que receberam dietas: 1. grupo controle, 2. grupo Nori e 3. grupo Wakame com vit E e 3 grupos similares sem vit E. Nas dietas com vit E, Nori produziu uma redução no crescimento e as duas algas provocaram uma acumulação de vit E hepática, redução da vit E plasmática e aumento em TBARS em plasma e fígado. Em contraste, quando as algas foram oferecidas em dietas sem vitamina E, o grupo Nori recuperou sua capacidade de crescimento, manteve maior reserva de vit E no fígado do que o grupo controle deficiente em vit E e o consumo de ambas as algas resultou em TBARS plasmáticos mais baixos do que nos ratos do grupo controle deficientes em vitamina E, indicando que essas algas são melhor aceitas quando oferecidas sem vit E. E, também, as algas melhoraram a capacidade de excreção do intestino sem afetar sua função de absorção.

Number of Patients Eligible for PCSK9 Inhibitors Based on Real-world Data From 2.5 Million Patients.

INTRODUCTION AND OBJECTIVES: PCSK9 inhibitors (PCSK9i) are safe and effective lipid-lowering drugs. Their main limitation is their high cost. The aim of this study was to estimate the number of patients eligible for treatment with PCSK9i according to distinct published criteria. METHODS: Data were obtained from the Information System for the Development of Research in Primary Care. Included patients were equal to or older than 18 years and had at least 1 low-density lipoprotein cholesterol measurement recorded between 2006 and 2014 (n = 2 500 907). An indication for treatment with PCSK9i was assigned according to the following guidelines: National Health System, Spanish Society of Arteriosclerosis, Spanish Society of Cardiology, National Institute for Health and Care Excellence, and the European Society of Cardiology/European Atherosclerosis Society Task Force. Lipid-lowering treatment was defined as optimized if it reduced low-density lipoprotein levels by ≥ 50% and adherence was > 80%. RESULTS: Among the Spanish population aged 18 years or older, the number of possible candidates to receive PCSK9i in an optimal lipid-lowering treatment scenario ranged from 0.1% to 1.7%, depending on the guideline considered. The subgroup of patients with the highest proportion of potential candidates consisted of patients with familial hypercholesterolemia, and the subgroup with the highest absolute number consisted of patients in secondary cardiovascular prevention. CONCLUSIONS: The number of candidates to receive PCSK9i in conditions of real-world clinical practice is high and varies widely depending on the recommendations of distinct scientific societies.

Concordancia entre la medición directa y el valor estimado de colesterol de LDL en pacientes ambulatorios / Concordance between direct measurement and estimated LDL cholesterol in outpatients / Concordância entre medição direta e colesterol LDL estimado em pacientes ambulatoriais

Los laboratorios clínicos estiman la concentración del colesterol asociado a la lipoproteína de baja densidad (cLDL) mediante la ecuación de Friedewald; sin embargo, ésta presenta una notable desviación cuando la concentración sérica de triglicéridos se encuentra elevada. Se compararon 4.644 resultados de cLDL valorados en el laboratorio central del Hospital Edgardo Rebagliati Martins (Lima-Perú), mediante el ensayo directo homogéneo, con los valores estimados por las ecuaciones de Friedewald, Anandaraja, Chen, Vujovic, Córdova y de regresión múltiple. Además, se estratificaron los resultados en 5 grupos en función de las concentraciones de triglicéridos para determinar la influencia que ejerce el nivel de triglicéridos sobre dichas ecuaciones. En el total de las estimaciones, las ecuaciones de regresión y Vujovic mostraron los menores sesgos de -3,00 y -2,90 mg/dL, respectivamente. Asimismo, ambas ecuaciones presentaron un grado de acuerdo sustancial con la determinación directa y un menor error sistemático en los tres niveles de decisión clínica para el cLDL; sin embargo, la ecuación de regresión presentó una mejor performance para estimar el cLDL en concentraciones de triglicéridos ≥401 mg/dL. Se concluye que la ecuación de regresión presenta bajo error analítico, además de mostrar una buena concordancia con el método directo, incluso a concentraciones altas de triglicéridos.

Clinical laboratories estimate the concentration of low-density lipoprotein cholesterol (LDLc) associated with the Friedewald equation, but the latter shows a significant deviation when the serum triglyceride concentration is elevated. A total of 4644 LDLc values assessed at the central laboratory of the Edgardo Rebagliati Martins Lima-Perú Hospital were compared by means of the homogeneous direct assay with the values estimated by the Friedewald, Anandaraja, Chen, Vujovic, Córdova and multiple regression equations. Besides, the results were stratified into 5 groups based on triglyceride concentrations to determine the influence exerted by the triglyceride level on these equations. In the total of the estimates, the regression equations and Vujovic showed the lowest biases of -3.00 and -2.90 mg/dL respectively. Likewise, both equations presented a degree of substantial agreement with the direct determination and a smaller systematic error in the three levels of clinical decision for LDLc. However, the regression equation showed a better performance for estimating LDLc at triglyceride concentrations ≥401 mg/dL. It is concludeasdasdd that the regression equation presents low analytical error, besides showing a good concordance with the direct method even at high triglyceride concentrations.

Laboratórios clínicos calculam a concentração do colesterol associado à lipoproteína de baixa densidade (LDLc), utilizando a equação de Friedewald; no entanto ela apresenta um desvio significativo quando a concentração sérica de triglicerídeos está elevada. 4644 resultados de LDLc foram comparados avaliados no laboratório central do Hospital Edgardo Rebagliati Martins (Lima-Peru), por ensaio directo homogêneo, com os valores estimados pelas equações Friedewald, Anandaraja, Chen, Vujovic, Córdova e de regressão múltipla. Além disso, foram estratificados os resultados em cinco grupos com base nas concentrações de triglicerídeos para determinar a influência que exerce o nível de triglicerídeos sobre tais equações. No total das estimativas, as equações de regressão e Vujovic mostraram os menores vieses de -3,00 e -2,90 mg/DL, respectivamente. Também, ambas as equações apresentaram um grau substancial de acordo com a determinação direta e um menor erro sistemático nos três níveis de decisão clínica para o LDLc; contudo, a equação de regressão apresentou melhor desempenho para estimar o LDLc em concentrações de triglicerídeos ≥401 mg/dL. Conclui-se que a equação de regressão apresenta baixo erro analítico, além de mostrar boa concordância com o método direto, mesmo em altas concentrações de triglicerídeos.

Causes of failure to achieve the low density lipoprotein cholesterol therapeutic target in patients with high and very high vascular risk controlled in Lipid and Vascular Risk Units. EROMOT study. / Causas de no consecución del objetivo terapéutico del colesterol de las lipoproteínas de baja densidad en pacientes de alto y muy alto riesgo vascular controlados en Unidades de Lípidos y Riesgo Vascular. Estudio EROMOT.

OBJECTIVES: Determination of the level of achievement of the low density lipoprotein cholesterol (LDL-C) therapeutic target in patients with high and very high vascular risk treated in Lipid Units, as well as the causes of non-achievement. PATIENTS AND METHOD: Multicentre retrospective observational study that included patients over 18 years with high and very high vascular risk, according to the criteria of the 2012 European Guidelines on Cardiovascular Disease Prevention, referred consecutively to Lipid Units between January and June 2012 and with follow-up two years after the first visit. RESULTS: The study included a total of 243 patients from 16 lipid units. The mean age was 52.2 years (SD 13.7), of whom 62.6% were males, and 40.3% of them were very high risk. At the first visit, 86.8% (25.1% in combination) and 95.0% (47.3% in combination) in the second visit (P<.001) were treated with lipid-lowering treatment. The therapeutic target was achieved by 28% (95 CI: 22.4-34.1). As regards the causes of non-achievement, 24.6% were related to the medication (10.3% maximum tolerated dose and 10.9% due to the appearance of adverse effects), 43.4% due to the physician (19.4% by inertia, 13.7% considering that target already reached), and 46.9% due to the patient, highlighting the therapeutic non-compliance (31,4%). CONCLUSIONS: LDL-C targets were achieved in about one-third of patients. The low adherence of the patient, followed by medical inertia are the most frequent causes that can explain these results.

Tendencias actuales del uso de las estatinas en dislipidemias y otros efectos extralipídicos / Current trends of the use of statins for dyslipidemias and other extra lipid effects

Introducción: Los pacientes con afecciones ateroscleróticas suelen presentar concentraciones intermedias de colesterol unido a lipoproteínas de baja densidad, lo que refleja la importancia de la interacción con otros factores de riesgo. El tratamiento con estatinas mejora el pronóstico, especialmente el tratamiento intensivo, e independientemente de los valores de colesterol, lo cual hace que se deba considerar esta estrategia terapéutica como una opción y por extensión, todos los pacientes con enfermedad vascular establecida.Objetivo: Examinar las tendencias actuales en el uso terapéutico de las estatinas.Fuente de datos: se realizó una revisión bibliográfica entre 2010-2015 en las bases de datos MedLine, Hinari, Cochrane, PubMed; de revistas líderes en la publicación de temas y artículos de interés.Síntesis de los datos: Las estatinas son fármacos eficaces para disminuir la concentración de colesterol y los triglicéridos en la circulación sanguínea. Además, aumentan moderadamente el colesterol unido a lipoproteínas de alta densidad y disminuyen la incidencia de enfermedad cardiovascular aterosclerótica, por lo que se las considera medicamentos de primera elección en el tratamiento de la dislipemia aterogénica. Se ha demostrado que el tratamiento hipolipemiante con estatinas, evita la progresión de la enfermedad hacia el episodio agudo.Conclusiones: Se actualizó que el efecto de las estatinas juega un papel fundamental en los pacientes con arteriopatía. Es conveniente iniciar el tratamiento lo más precoz posible y extenderlo a sectores arteriales como el cerebrovascular y el periférico(AU)

Introduction: Patients with acute atherosclerotic conditions usually present with moderate cholesterol concentrations together with low-density lipoprotein levels, which indicates the importance of the interactions with other risk factors. Statin therapy improves prognosis after the occurrence of an acute coronary syndrome, especially in intensive care and regardless of cholesterol values, which leads to consider this therapeutic strategy as an option to be extended to all the patients with a set vascular disease.Objective: To examine the present tendencies in the statin therapy.Data sourse: A literature review was made from 2010 to 2015 in MedLine Hinari, Cochrane and PubMed databases and in leading journals in the publication of topics and articles of interest.Data synthesis: Statins are effective drugs to decrease the blood cholesterol and triglyceride levels. Besides, they increase the high density lipoprotein cholesterol and reduce the incidence of atherosclerotic cardiovascular disease, therefore, they are considered first-choice drugs for the treatment of atherogenic dyslipidemia. It has been proved that hypolipidemic treatment with statin avoids the progression of the disease into the acute stage.Conclusions: The review provides an update on the fundamental role of statins in the treatment of patients with artheropathy. It is desirable to initiate the treatment as early as possible and to extend it to other arterial areas such as cerebrovascular and peripheral ones(AU)

Tendencias actuales del uso de las estatinas en dislipidemias y otros efectos extralipídicos / Current trends of the use of statins for dyslipidemias and other extra lipid effects

Introducción: Los pacientes con afecciones ateroscleróticas suelen presentar concentraciones intermedias de colesterol unido a lipoproteínas de baja densidad, lo que refleja la importancia de la interacción con otros factores de riesgo. El tratamiento con estatinas mejora el pronóstico, especialmente el tratamiento intensivo, e independientemente de los valores de colesterol, lo cual hace que se deba considerar esta estrategia terapéutica como una opción y por extensión, todos los pacientes con enfermedad vascular establecida. Objetivo: Examinar las tendencias actuales en el uso terapéutico de las estatinas. Fuente de datos: se realizó una revisión bibliográfica entre 2010-2015 en las bases de datos MedLine, Hinari, Cochrane, PubMed; de revistas líderes en la publicación de temas y artículos de interés. Síntesis de los datos: Las estatinas son fármacos eficaces para disminuir la concentración de colesterol y los triglicéridos en la circulación sanguínea. Además, aumentan moderadamente el colesterol unido a lipoproteínas de alta densidad y disminuyen la incidencia de enfermedad cardiovascular aterosclerótica, por lo que se las considera medicamentos de primera elección en el tratamiento de la dislipemia aterogénica. Se ha demostrado que el tratamiento hipolipemiante con estatinas, evita la progresión de la enfermedad hacia el episodio agudo. Conclusiones: Se actualizó que el efecto de las estatinas juega un papel fundamental en los pacientes con arteriopatía. Es conveniente iniciar el tratamiento lo más precoz posible y extenderlo a sectores arteriales como el cerebrovascular y el periférico(AU)

Introduction: Patients with acute atherosclerotic conditions usually present with moderate cholesterol concentrations together with low-density lipoprotein levels, which indicates the importance of the interactions with other risk factors. Statin therapy improves prognosis after the occurrence of an acute coronary syndrome, especially in intensive care and regardless of cholesterol values, which leads to consider this therapeutic strategy as an option to be extended to all the patients with a set vascular disease. Objective: To examine the present tendencies in the statin therapy. Data sourse: A literature review was made from 2010 to 2015 in MedLine Hinari, Cochrane and PubMed databases and in leading journals in the publication of topics and articles of interest. Data synthesis: Statins are effective drugs to decrease the blood cholesterol and triglyceride levels. Besides, they increase the high density lipoprotein cholesterol and reduce the incidence of atherosclerotic cardiovascular disease, therefore, they are considered first-choice drugs for the treatment of atherogenic dyslipidemia. It has been proved that hypolipidemic treatment with statin avoids the progression of the disease into the acute stage. Conclusions: The review provides an update on the fundamental role of statins in the treatment of patients with artheropathy. It is desirable to initiate the treatment as early as possible and to extend it to other arterial areas such as cerebrovascular and peripheral ones(AU)

[Lipid control in patients with coronary artery disease in a healthcare area in Cáceres (Spain): LIPICERES study]. / Control lipídico en pacientes con enfermedad coronaria del Área de Salud de Cáceres (España): estudio LIPICERES.

INTRODUCTION AND OBJECTIVES: Current guidelines recommend a low-density lipoprotein cholesterol (LDLc) target of <70mg/dl for patients with coronary artery disease. Despite the well-established benefits of strict lipid control, the most recent studies show that control rate of lipid targets are alarmingly low. An analysis was performed on the lipid targets attained according to current guidelines for the prevention of cardiovascular disease in coronary patients in a Caceres healthcare area. METHODS: An observational and cross-sectional study was carried out in a healthcare area in Caceres (Spain). The study included a total of 741 patients admitted for coronary disease between 2009 and 2015 with available lipid profile in the last 3 years Total cholesterol, high-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), triglycerides (TG) and non-HDLc were analysed. RESULTS: The majority (74.4%) of patients were male, with a mean age of 68.5±13.1 years; 76.3±11.8 for women and 65.8±12.6 for men (P<.001). A total of 52.3% patients achieved the LDLc target of <70mg/dl, with no gender differences. Only 44.8% of the patients <55 years achieved their lipid targets, compared to 59.3% of the patients >75 years. About 68.2% of men had an HDLc>40mg/dl, and 54.8% of women had an HDLc>50mg/dl. Overall, 79.4% of patients had a TG<150mg/dl, with no gender differences, and 59.8% had a non-HDLc<100mg/dl. CONCLUSIONS: Approximately one half of patients with coronary disease do not achieve their target lipid levels as defined in the European guidelines, and this rate is less than reported in previous studies. There are no gender differences in achieving lipid goals, and age is a predictor of adherence.

Derivación y validación de una ecuación para estimar el colesterol ligado a lipoproteínas de baja densidad en una población de Lima, Perú / Derivation and validation of an equation to determine cholesterol-low density lipoproteins in a population of Lima, Peru

Introducción. Numerosos estudios han demostrado una fuerte asociación entre el aumento de la concentración sérica del colesterol de las lipoproteínas de baja densidad (LDLc) y la incidencia de la enfermedad coronaria (EC). Objetivos. Derivar y validar la performance de una nueva ecuación para estimar el LDLc. Diseño. Estudio observacional y descriptivo. Institución. Hospital Edgardo Rebagliati Martins, Lima, Perú. Material. Informes de perfil lipídico. Intervenciones. La muestra de 4 644 informes de perfil lipídico extraídos de los archivos del laboratorio central, correspondiente a sujetos de ambos sexos, que presentaban edades entre 18 a 75 años, fue repartida en dos grupos. Del primer grupo conformado por 2 136 informes se derivó la ecuación para estimar el LDLc, mediante análisis de regresión múltiple. El segundo grupo conformado por 2 508 informes sirvieron para validar la performance de la nueva ecuación mediante la comparación con la medida del LDLc por el método directo homogéneo y estimado por la fórmula de Friedewald. Principal medida de resultados. Concentración sérica del LDLc. Resultados. La fórmula de Friedewald y la nueva ecuación infraestimaron el LDLc, obteniéndose sesgos de 14,01 mg/dL y 5,52 mg/dL, respectivamente, con respecto al método directo. Los errores sistemáticos en los tres niveles de decisión clínica para el LDLc resultaron ser mayores para la fórmula de Friedewald (12,6%, 12,0% y 11,7%) comparados a la nueva ecuación (4,2%, 5,7% y 6,7%). El factor de corrección de sesgo, que valora la exactitud, resultó ser más alto y más cerca de la línea de perfecta concordancia para la nueva ecuación, en toda la muestra y cuando esta se estratificó por niveles de triglicéridos. Conclusiones. La nueva ecuación ofrece una mayor exactitud y bajo error analítico comparada a la fórmula de Friedewald para estimar el LDLc, en los tres niveles de decisión clínica y en sueros con diferentes valores de triglicéridos.

Introduction: Various studies have shown a strong association between the increase in cholesterol low density lipoproteins (LDLc) serum concentration and the incidence of coronary heart disease. Objectives: To derive and validate the performance of a new equation to estimate the LDLc. Design: Observational and descriptive study. Institution: Hospital Edgardo Rebagliati Martins, Lima, Peru. Material: 4 644 lipid profile reports taken from the files of the hospital's central laboratory, belonging to subjects of bot. sexes, between 18 and 75 years old. Interventions: The sample consisted of 4 644 lipid profile reports obtained from the files of the hospital's central laboratory, and belonged to subjects of both sexes aged 18-75 years. It was divided into two groups: the first group was represented by 2 136 reports, and was used to derive the equation to estimate the LDLc by using multiple regression analysis; the second group comprised 2 508 reports that served to validate the performance of the new equation compared with the LDLc measurement by the homogeneous direct method and estimated by the Friedewald formula. Main outcome measure: LDLc serum concentration. Results: The Friedewald formula and the new equation underestimated the LDLc with a shortfall of 14.01 mg/dL and 5.52 mg/dL, respectively, with regard to the direct method. Systematic errors in the three clinical decision levels for LDL cholesterol were found to be higher for the Friedewald formula (12.6%, 12.0 %, and 11.7%) compared to the new equation (4.2%, 5.7% and 6.7%). The bias correction factor, which assessed accuracy, turned out to be higher and closer to the line of perfect match for the new equation, both in the whole sample and when the entire sample was stratified by levels of triglycerides. Conclusions: The new equation provided greater accuracy and lower analytical error compared to the Friedewald formula to estimate the LDL cholesterol in the three clinical decision levels and with different values of serum triglycerides.

Attainment of LDL Cholesterol Treatment Goals in Children and Adolescents With Familial Hypercholesterolemia. The SAFEHEART Follow-up Registry.

INTRODUCTION AND OBJECTIVES: Little is known about the characteristics of persons with familial hypercholesterolemia (FH) younger than 18 years, the lipid-lowering therapy used in these patients, and the lipid goals reached in real life. Our aim was to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients younger than 18 years enrolled in a large national registry. METHODS: We analyzed patients younger than 18 years enrolled in a large ongoing registry of molecularly-defined patients with FH in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was analyzed in relation to the use of lipid-lowering therapy. RESULTS: We enrolled 392 individuals younger than 18 years. Of these, 217 were molecularly-diagnosed FH patients and had a complete follow-up. The median follow-up time was 4.69 years (interquartile range, 2.48-6.38 years), 68.2% of FH patients were on statins, and 41.5% patients had LDL-C < 130mg/dL. Statin use was the only predictor of LDL-C goal attainment. CONCLUSIONS: This study shows that a high proportion of FH patients younger than 18 years have high LDL-C levels and fail to achieve recommended LDL-C targets. Statin use was the only independent predictor of LDL-C goal achievement. No safety concerns were detected during follow-up. These results indicate that many FH patients are not adequately controlled and that there is still room for treatment improvement.

[Not Available]. / Efecto de esteroles vegetales en la reducción del colesterol plasmático: ensayo clínico, controlado, aleatorizado, cruzado y doble ciego.

Introducción: la hipercolesterolemia es uno de los principales factores de riesgo en la enfermedad cardiovascular. Los esteroles vegetales se han postulado como agentes reguladores y beneficiosos para el control de esta.Objetivo: analizar el efecto de los esteroles vegetales añadidos en una leche en la reducción del colesterol plasmático en adultos jóvenes.Métodos: ensayo clínico, controlado, aleatorizado, doble ciego y cruzado. Los esteroles (2,24 g diarios) fueron administrados en dos tomas de 350 ml de una leche comercial desnatada, durante dos periodos de 3 semanas, separados por una "fase de lavado" de 2 semanas, en el grupo experimental. Al grupo control se le administró la misma cantidad de leche desnatada, sin esteroles. Tanto al inicio como al final de cadaperiodo de intervención se extrajeron muestras sanguíneas. Se analizaron la composición corporal, hábitos de salud y los siguientes marcadores sanguíneos: perfil lipídico, hematológico, inflamación, etc.Resultados: se incluyeron 54 personas en el estudio con una edad media de 38,8 ± 7,3 años. La diferencia porcentual entre los marcadores basales y finales para el colesterol total, colesterol-LDL, colesterol-HDL, triglicéridos y colesterol no-HDL fueron del 9,73%, 12,5%, 1,9%, 3,15% y 13,2%, respectivamente. Se obtuvieron diferencias estadísticamente significativas entre el grupo experimental y el grupo control, para todos los marcadores analizados excepto para los triglicéridos.Conclusión: los esteroles vegetales suministrados en un alimento de consumo habitual, como la leche, pueden ser una estrategia terapéutica no farmacológica para el control de la hipercolesterolemia de alto interés sanitario.

[Consensus on objectives and action guidelines on low density lipoproteins-cholesterol control in very high risk cardiovascular patients]. / Consenso sobre los objetivos y pautas de actuación en el control del colesterol ligado a lipoproteínas de baja densidad en pacientes de muy alto riesgo cardiovascular.

INTRODUCTION: Cardiovascular disease is the leading cause of death in developed countries. Among cardiovascular disease risk factors one of the most relevant is low-density lipoprotein-associated cholesterol (LDL-c), but there is controversy about the methods used to control it. The aim was to obtain an expert opinion to clarify the most relevant issues regarding the control of dyslipidemia in very high cardiovascular risk patients. MATERIALS AND METHODS: A survey with 55 items, stratified into 4 blocks: LDL-c as a therapeutic target, therapeutic goals, causes of the failure to achieve LDL-c goals, and recommendations to optimize their achievement, was addressed to 41 specialists (Cardiology and Internal Medicine) using the Delphi method to achieve professional consensus criteria. RESULTS: A high consensus was reached among all items, in line with the European recommendations. The panelists considered that the goal of 70mg/dl for LDL-c for high cardiovascular disease risk (mainly vascular disease, diabetes mellitus, and renal failure), using combined treatment when necessary. Lack of adherence and therapeutic inertia were considered the main reasons for treatment failure. CONCLUSION: The Spanish experts show an elevated consensus with the European recommendations, confirming the LDL-c control target of <70mg/dl. The simplification of the guidelines and the combined treatment may favor an improvement the achievement of lipid target goals.

[Association between venous thrombosis and dyslipidemia]. / Asociación entre enfermedad tromboembólica venosa y dislipidemia.

BACKGROUND AND OBJECTIVE: Venous and arterial thrombosis, despite being historically considered as distinct conditions, share certain risk factors. Dyslipidemia is a clinical condition with a relatively high prevalence in the population and has been associated with an increased thrombotic risk. Lipids and lipoproteins modulate the expression and/or function of thrombotic, fibrinolytic and rheological factors. PATIENTS AND METHOD: We have developed a descriptive, retrospective, comparative, cross-sectional study including a group of 313 patients with venous thromboembolism (VTE). We collected basic demographic data, cardiovascular risk factors and thrombotic complications. All patients were subjected to a lipid profile study with determination of total cholesterol, high density lipoprotein cholesterol (cHDL), low density lipoprotein cholesterol (cLDL) and triglycerides. RESULTS: The multivariable analysis showed that dyslipidemia was a risk factor for VTE (odds ratio [OR] 3.87, 95% confidence interval [95% CI] 2.72-5.56; P<.0001). Of a total of 313 patients included in the study, 31% (n=97) had a recurrent thrombotic event and 23% (n=72) developed post-thrombotic syndrome. cHDL levels below 35 mg/dl and cLDL levels higher than 180 mg/dl represented risk factors for the development of recurrent thrombosis, OR 3.12 (95% CI 1.35-7.74; P=.008) and OR 2.35 (95% CI 1.24-4.45; P=.008), respectively, and post-thrombotic syndrome, OR 3.44 (95% CI 1.43-8.83; P=.005) and OR 2.35 (95% CI 1.24-4.45; P=.008). CONCLUSIONS: Our study confirmed the association between dyslipidemia and VTE and showed a risk of thrombosis nearly 4 times higher in individuals with this disease. In addition, alterations in the lipid profile were also related to a higher prevalence of thrombotic complications, recurrence and post-thrombotic syndrome.