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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.

Resumen Introduccion y objetivos Los inhibidores de la PCSK9 (iPCSK9) son farmacos hipolipemiantes eficaces y seguros pero con un elevado coste. El objetivo del estudio es estimar el numero de pacientes candidatos a recibir iPCSK9 segun los diferentes criterios publicados. Metodos Los datos provienen del Sistema de Informacion para la Investigacion en Atencion Primaria. Se incluyo a pacientes de edad ≥ 18 anos con al menos una determinacion de colesterol unido a lipoproteinas de baja densidad entre 2006 y 2014 (n = 2.500.907). Los criterios de indicacion terapeutica de iPCSK9 analizados fueron: Sistema Nacional de Salud, Sociedad Espanola de Arteriosclerosis, Sociedad Espanola de Cardiologia, National Institute for Health and Care Excellence y Sociedad Europea de Cardiologia/European Atherosclerosis Society Task Force. Se definio como tratamiento lipidico optimizado el que alcanzara una reduccion del colesterol unido a lipoproteinas de baja densidad ≥ 50% y un cumplimiento > 80%. Resultados En la poblacion espanola de 18 o mas anos el numero de posibles candidatos a recibir iPCSK9 en un escenario de tratamiento hipolipemiante optimo oscila entre el 0,1 y el 1,7% segun los diferentes criterios. El subgrupo con mayor porcentaje de candidatos seria el de los pacientes con hipercolesterolemia familiar, y el mayor numero absoluto vendria de los pacientes en prevencion secundaria. Conclusiones El numero de posibles candidatos a recibir iPCSK9 en condiciones de practica clinica es muy alto y varia mucho segun las recomendaciones de las diferentes sociedades cientificas.

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.

Cardiovascular risk in heterozygous familial hypercholesterolaemia (HeFH) is driven by LDL cholesterol levels. Since lipid response to statin therapy presents individual variation, this study aimed to compare mean LDL and non-HDL cholesterol reductions and their variability achieved with different types and doses of the most frequently prescribed statins.Among primary hypercholesterolaemia cases on the Spanish Arteriosclerosis Society registry, 2894 with probable/definite HeFH and complete information on drug therapy and lipid profile were included. LDL cholesterol reduction ranged from 30.2 ± 17.0% with simvastatin 10 mg to 48.2 ± 14.7% with rosuvastatin 40 mg. After the addition of ezetimibe, an additional 26, 24, 21 and 24% reduction in LDL cholesterol levels was obtained for rosuvastatin, 5, 10, 20 and 40 mg, respectively. Subjects with definite HeFH and a confirmed genetic mutation had a more discrete LDL cholesterol reduction compared to definite HeFH subjects with no genetic mutation. A suboptimal response (15% or30% reduction in LDL cholesterol levels, respectively with low-/moderate-intensity and high-intensity statin therapy) was observed in 13.5% and, respectively, 20.3% of the subjects.According to the LDL cholesterol reduction in HeFH patients, the ranking for more to less potent statins was rosuvastatin, atorvastatin and simvastatin; however, at maximum dosage, atorvastatin and rosuvastatin were nearly equivalent. HeFH subjects with positive genetic diagnosis had a lower lipid-lowering response. Approximately 1 in 5 patients on high-intensity statin therapy presented a suboptimal response.

Hipercolesterolèmia familiar; Aterosclerosi; Puntuació de risc genètic Familial hypercholesterolemia; Atherosclerosis; Genetic risk scores Hipercolesterolemia familiar; Aterosclerosis; Puntuaciones de riesgo genético Familial hypercholesterolemia (FH) is associated with mutations in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes. A pathological variant has not been identified in 30–70% of clinically diagnosed FH patients, and a burden of LDL cholesterol (LDL-c)-raising alleles has been hypothesized as a potential cause of hypercholesterolemia in these patients. Our aim was to study the distribution of weighted LDL-c-raising single-nucleotide polymorphism (SNP) scores (weighted gene scores or wGS) in a population recruited in a clinical setting in Catalonia. The study included 670 consecutive patients with a clinical diagnosis of FH and a prior genetic study involving 250 mutation-positive (FH/M+) and 420 mutation-negative (FH/M−) patients. Three wGSs based on LDL-c-raising variants were calculated to evaluate their distribution among FH patients and compared with 503 European samples from the 1000 Genomes Project. The FH/M− patients had significantly higher wGSs than the FH/M+ and control populations, with sensitivities ranging from 42% to 47%. A wGS based only on the SNPs significantly associated with FH (wGS8) showed a higher area under the receiver operating characteristic curve, and higher diagnostic specificity and sensitivity, with 46.4% of the subjects in the top quartile. wGS8 would allow for the assignment of a genetic cause to 66.4% of the patients if those with polygenic FH are added to the 37.3% of patients with monogenic FH. Our data indicate that a score based on 8 SNPs and the75th percentile cutoff point may identify patients with polygenic FH in Catalonia, although with limited diagnostic sensitivity and specificity This research was funded by the Instituto de Salud Carlos III (ISCIII), and Fondo Europeo de DesarrolloRegional (FEDER) “Una manera de hacer Europa”, grants PI14/01648 (to F.B.-V. and J.M.M.-C.) and PI18/00164(to F.B.-V.), as well as by Fundacióla Maratóde TV3 grant 20152431 (to F.B.-V.), Centro de Investigación Biomédicaen Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), and Centro de Investigación Biomédicaen Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN). CIBERDEM and CIBEROBN are ISCIII projects

Resumen Objetivos Determinar el grado de consecucion del objetivo terapeutico del colesterol de las lipoproteinas de baja densidad (cLDL) en pacientes de alto y muy alto riesgo vascular atendidos en las unidades de lipidos, asi como las causas de no consecucion. Pacientes y metodo Estudio observacional retrospectivo multicentrico. Se incluyo a los pacientes mayores de 18 anos con alto o muy alto riesgo vascular, segun los criterios de la Guia europea de prevencion cardiovascular de 2012, remitidos de forma consecutiva a las unidades de lipidos entre enero y junio del 2012 y con seguimiento a los 2 anos de la primera visita. Resultados Se incluyo a 243 pacientes procedentes de 16 unidades de lipidos. La edad media fue de 52,2 anos (DE 13,7) con un 62,6% de varones. Un 40,3% eran de muy alto riesgo. En la primera visita seguian tratamiento hipolipidemiante el 86,8% (en combinacion 25,1%) y en la segunda visita el 95,0% (en combinacion 47,3%) (p Conclusiones Se consiguieron los objetivos de cLDL en cerca de un tercio de los pacientes. La baja adherencia del paciente, seguida de la inercia medica, son las causas mas frecuentes que pueden explicar estos resultados.

Objectives To determine the extent to which low-density lipoprotein cholesterol (LDL-C) therapeutic targets are achieved in patients with high and very high vascular risk treated in lipid units, and the reasons why these targets are not met. Patients and method Observational and retrospective multi-centre study. Patients over the age of 18 with high or very high vascular risk according to the criteria set forth by the 2012 European guidelines on cardiovascular disease prevention who were consecutively referred to lipid units between January and June 2012 and with follow-up two years after the first visit were included. Results 243 patients from 16 lipid units were enrolled. The mean age was 52.2 years (SD 13.7) and 62.6% of the patients were male. 40.3% were classified as very high risk. At the first visit, 86.8% were on lipid-lowering treatment (25.1% on combination therapy), which rose to 95.0% at the second visit (47.3% on combination therapy) (p Conclusions LDL-C therapeutic targets were achieved in around one third of patients. Patient non-adherence, followed by clinical inertia, are the primary causes that could explain these results.

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.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.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%).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.