Análisis geoestadístico desde el laboratorio clínico en prevención cardiovascular para atención primaria / Geostatistical analysis from the clinical laboratory in cardiovascular prevention for primary care

Introducción y objetivos: Las enfermedades cardiovasculares continúan encabezando la mortalidad en España. Las técnicas de análisis geoestadístico en el laboratorio clínico son herramientas innovadoras que permiten el diseño de nuevas estrategias en prevención primaria de enfermedad cardiovascular. El objetivo fue estudiar la prevalencia y geolocalización de dislipidemias en las áreas sanitarias de estudio para implementar estrategias de prevención en atención primaria. Se llevó a cabo un estudio de cohorte retrospectivo de los niveles de colesterol unido a proteínas de baja densidad, triglicéridos y lipoproteína (a) en los años 2019 y 2020. Además, se realizó un análisis geoestadístico que incluyó la representación en mapas coropléticos y la detección de clústeres de agrupación; para ello, se utilizó la información geográfica en formato de código postal incluida en los datos demográficos de cada analítica. Resultados: Los datos analíticos incluidos en el estudio fueron triglicéridos (n=365.384), colesterol unido a proteínas de baja densidad (n=289.594) y lipoproteína (a) (n=502). Se identificaron las áreas con mayor y menor porcentaje de casos para los puntos de corte establecidos de cLDL> 190mg/dl y TG> 150mg/dl. Se detectaron 2clústeres de agrupación con significación estadística para cLDL> 190mg/dl y un total de 6 clústeres para los valores de TG> 150mg/dl. Conclusiones: La detección de clústeres, así como la representación de mapas coropléticos, pueden ser de gran ayuda en la detección de áreas geográficas que requieran de mayor atención para intervenir en el riesgo cardiovascular.(A)U

Introduction and objectives: Cardiovascular diseases continue to lead the ranking of mortality in Spain. The implementation of geostatistical analysis techniques in the clinical laboratory are innovative tools that allow the design of new strategies in primary prevention of cardiovascular disease. The aim of this study was to study the prevalence and geolocation of severe dyslipidemia in the health areas under study in order to implement prevention strategies in primary care. A retrospective cohort study of low-density protein-bound cholesterol, triglyceride and lipoprotein (a) levels in the years 2019 and 2020 were carried out. In addition, a geostatistical analysis was performed including representation in choropleth maps and the detection of clustering clusters, using geographic information in zip code format included in the demographic data of each analytic. Results: The analytical data included in the study were triglycerides (n=365,384), low density protein-bound cholesterol (n=289,594) and lipoprotein to lipoprotein (a) (n=502). Areas with the highest and lowest percentage of cases were identified for the established cut-off points of LDL-C>190mg/dL and TG>150mg/dL. Two clustering clusters with statistical significance were detected for cLDL>190mg/dL and a total of 6 clusters for TG values>150mg/dL. Conclusions: The detection of clusters, as well as the representation of choropleth maps, can be of great help in detecting geographic areas that require greater attention to intervene and improve cardiovascular risk.(AU)

Geostatistical analysis from the clinical laboratory in cardiovascular prevention for primary care. / Análisis geoestadístico desde el laboratorio clínico en prevención cardiovascular para atención primaria.

INTRODUCTION AND OBJECTIVES: Cardiovascular diseases continue to lead the ranking of mortality in Spain. The implementation of geostatistical analysis techniques in the clinical laboratory are innovative tools that allow the design of new strategies in primary prevention of cardiovascular disease. The aim of this study was to study the prevalence and geolocation of severe dyslipidemia in the health areas under study in order to implement prevention strategies in primary care. A retrospective cohort study of low-density protein-bound cholesterol, triglyceride and lipoprotein (a) levels in the years 2019 and 2020 were carried out. In addition, a geostatistical analysis was performed including representation in choropleth maps and the detection of clustering clusters, using geographic information in zip code format included in the demographic data of each analytic. RESULTS: The analytical data included in the study were triglycerides (n=365,384), low density protein-bound cholesterol (n=289,594) and lipoprotein to lipoprotein (a) (n=502). Areas with the highest and lowest percentage of cases were identified for the established cut-off points of LDL-C>190mg/dL and TG>150mg/dL. Two clustering clusters with statistical significance were detected for cLDL>190mg/dL and a total of 6 clusters for TG values>150mg/dL. CONCLUSIONS: The detection of clusters, as well as the representation of choropleth maps, can be of great help in detecting geographic areas that require greater attention to intervene and improve cardiovascular risk.

Laboratory Value-Based Innovation in Heart Failure Improves Patient Health-Related Outcomes.

BACKGROUND: NT-proBNP is emerging as a novel tool for improving management of patients with heart failure (HF). The concept of health-related outcomes as the primary endpoint for therapeutic intervention in chronic disease, such as HF, should be the focal point going forward. METHODS: We conducted a prospective real-world study in heart failure with reduced ejection fraction (HFrEF) patients. The main target was to evaluate the impact on patient's health-related outcomes of a personalized medical follow-up procedure, based on a laboratory model of risk stratification supported by NT-proBNP. One hundred and five consecutive patients admitted to the Hospital Heart-Failure unit were stratified into three groups (low, medium, and high risk) and prospective follow-ups during the 12 months post discharge. RESULTS: It was found that patients under this new approach experienced early and robust improvements in patient health-related outcomes with consistency in most domains which persisted beyond 12 months post follow-up. Improvements in health related quality of life score (HRQLS) was observed over the time of the study. After 6 months we found a significant improvement in HRQLS of 18.2% (from 76.5 ± 22.4 to 95.0 ± 15.7) and 14.4% (from 76.5 ± 22.4 to 96.3 ± 15.9) after 12 months of follow-up (p < 0.001). The highest improvements were found in the symptom severity domain where patients reported an improvement of 22.6% after 6 months and 18.9% after 12 months (p < 0.001). The lowest scores were reported in the physical domain with increase of 11.0% and 4.3% after 6 months and 12 months (p = 0.089). Psychosocial domain and the ability to carry out the activities of normal life showed improvement as well. CONCLUSIONS: Our strategy based on NT-proBNP optimizes HFrEF management and represents a major new approach for clinical laboratories to improve patient health-related outcomes in HFrEF.

Incorporación de parámetros bioquímicos y algoritmos diagnósticos en el sistema informático de laboratorio para la detección precoz de alteraciones lipídicas desde las unidades de lípidos / Incorporation of biochemical parameters and diagnostic algorithms in the laboratory computer system for the early detection of lipid abnormalities from the lipid units

Introducción: La combinación de marcadores bioquímicos y el diseño e implementación de algoritmos diagnósticos en el sistema informático de los laboratorios podrían convertirse en herramientas muy potentes en la estratificación del riesgo cardiovascular. Objetivos: Implementar nuevos marcadores bioquímicos y algoritmos diagnósticos hasta ahora no disponibles para facilitar la estimación del riesgo cardiovascular y la orientación diagnóstica de las alteraciones lipídicas. Material y métodos: Estudio para la implementación de apolipoproteína B y de lipoproteína (a), así como la inclusión de diferentes algoritmos diagnósticos. Se ha realizado conjuntamente entre las diferentes unidades de lípidos de la Sociedad Española de Arteriosclerosis, Hospital Virgen Macarena de Sevilla, Hospital Juan Ramón Jiménez, Hospital Infanta Elena y Hospital de Río Tinto durante los años 2018 y 2019. Resultados: Se han aplicado 4 algoritmos diagnósticos en el sistema de información del laboratorio, que mostraron 9.985 pacientes totales con c-LDL>200mg/dl. Según el algoritmo diagnóstico, que se amplió para que incluyera ApoB, 8.182 determinaciones presentaban una apolipoproteína B>100mg/dl. Se determinaron 747 casos de lipoproteína (a), de las cuales un 30,65% fueron superiores a 50mg/dl. El 71,80% presentaban resultados compatibles con partículas de LDL pequeñas y densas. Conclusiones: La implementación de nuevos parámetros analíticos y el uso de algoritmos en los laboratorios en atención primaria permite identificar un número considerable de pacientes con diferentes alteraciones en el metabolismo lipídico que, junto con los factores de riesgo clásicos, podría contribuir a una correcta estratificación de riesgo y a evitar la progresión de la enfermedad cardiovascular.(AU)

Introduction: The combination of biochemical markers, together with the design and implementation of diagnostic algorithms in laboratory computer systems could become very powerful tools in the stratification of cardiovascular risk. Objectives: To implement new biochemical markers and diagnostic algorithms not yet available, in order to provide an estimation of cardiovascular risk and the diagnostic orientation of lipid alterations. Material and methods: Study of the implementation of apolipoprotein B and lipoprotein (a), as well as the inclusion of different diagnostic algorithms. This was carried out jointly by the different Lipid Units of the Spanish Society of Atherosclerosis, Hospital Virgen Macarena in Seville, Hospital Juan Ramón Jiménez, Hospital Infanta Elena, and Hospital de Río Tinto during 2018 and 2019. Results: The 4diagnostic algorithms entered into the Laboratory Information System, showed a total of 9,985 patients with c-LDL>200mg/dl. The diagnostic algorithm was extended to include Apo B, with 8,182 determinations showing an apolipoprotein B>100mg/dl). A total of 747 lipoprotein (a) were determined, of which 30.65% were> 50mg/dl. More than 2/3 (71.80%) showed results compatible with small and dense LDL particles. Conclusions: The implementation of new analytical parameters and algorithms in Primary Care laboratory results can identify a considerable number of patients with different alterations in lipid metabolism. This, together with the classic risk factors, could contribute to a correct risk stratification in preventing the progression of cardiovascular disease.(AU)

Biomarkers-based personalized follow-up in chronic heart failure improves patient's outcomes and reduces care associate cost.

BACKGROUND: Heart failure (HF) is a major and growing medical and economic problem, with high prevalence and incidence rates worldwide. Cardiac Biomarker is emerging as a novel tool for improving management of patients with HF with a reduced left ventricular ejection fraction (HFrEF). METHODS: This is a before and after interventional study, that assesses the impact of a personalized follow-up procedure for HF on patient's outcomes and care associated cost, based on a clinical model of risk stratification and personalized management according to that risk. A total of 192 patients were enrolled and studied before the intervention and again after the intervention. The primary objective was the rate of readmissions, due to a HF. Secondary outcome compared the rate of ED visits and quality of life improvement assessed by the number of patients who had reduced NYHA score. A cost-analysis was also performed on these data. RESULTS: Admission rates significantly decreased by 19.8% after the intervention (from 30.2 to 10.4), the total hospital admissions were reduced by 32 (from 78 to 46) and the total length of stay was reduced by 7 days (from 15 to 9 days). The rate of ED visits was reduced by 44% (from 64 to 20). Thirty-one percent of patients had an improved functional class score after the intervention, whereas only 7.8% got worse. The overall cost saving associated with the intervention was € 72,769 per patient (from € 201,189 to € 128,420) and €139,717.65 for the whole group over 1 year. CONCLUSIONS: A personalized follow-up of HF patients led to important outcome benefits and resulted in cost savings, mainly due to the reduction of patient hospitalization readmissions and a significant reduction of care-associated costs, suggesting that greater attention should be given to this high-risk cohort to minimize the risk of hospitalization readmissions.

Incorporation of biochemical parameters and diagnostic algorithms in the laboratory computer system for the early detection of lipid abnormalities from the lipid units. / Incorporación de parámetros bioquímicos y algoritmos diagnósticos en el sistema informático de laboratorio para la detección precoz de alteraciones lipídicas desde las unidades de lípidos.

INTRODUCTION: The combination of biochemical markers, together with the design and implementation of diagnostic algorithms in laboratory computer systems could become very powerful tools in the stratification of cardiovascular risk. OBJECTIVES: To implement new biochemical markers and diagnostic algorithms not yet available, in order to provide an estimation of cardiovascular risk and the diagnostic orientation of lipid alterations. MATERIAL AND METHODS: Study of the implementation of apolipoprotein B and lipoprotein (a), as well as the inclusion of different diagnostic algorithms. This was carried out jointly by the different Lipid Units of the Spanish Society of Atherosclerosis, Hospital Virgen Macarena in Seville, Hospital Juan Ramón Jiménez, Hospital Infanta Elena, and Hospital de Río Tinto during 2018 and 2019. RESULTS: The 4diagnostic algorithms entered into the Laboratory Information System, showed a total of 9,985 patients with c-LDL>200mg/dl. The diagnostic algorithm was extended to include Apo B, with 8,182 determinations showing an apolipoprotein B>100mg/dl). A total of 747 lipoprotein (a) were determined, of which 30.65% were> 50mg/dl. More than 2/3 (71.80%) showed results compatible with small and dense LDL particles. CONCLUSIONS: The implementation of new analytical parameters and algorithms in Primary Care laboratory results can identify a considerable number of patients with different alterations in lipid metabolism. This, together with the classic risk factors, could contribute to a correct risk stratification in preventing the progression of cardiovascular disease.

Particularidades genéticas y bioquímicas de la hipercolesterolemia familiar en el suroeste de la Península Ibérica / Genetics and biochemistry of familial hypercholesterolemia in Southwest of the Iberian Peninsula

Hasta el momento, la mayor parte de los casos de hipercolesterolemia familiar (60-80%) se atribuyen a variantes patogénicas en el gen LDLR. Solo un 1-5% de los casos se produce por variantes en el gen APOB y un 0-3% por variantes en el gen PCSK9. Existen gran variedad en mutaciones patogénicas conocidas del gen LDLR mientras que, para las que afectan al gen APOB, la de mayor incidencia es p.Arg3527Gln, descrita predominantemente en poblaciones de Centroeuropa y América del Norte. En la Península Ibérica el gen predominante afectado es el del receptor de LDL, similar al resto del mundo, siendo la afectación del gen APOB descrita en individuos del noroeste y anecdótica en el resto del territorio. Analizamos genéticamente la población asistida en el primer año de una consulta de lípidos del suroeste de España con puntuación≥6 puntos de las clínicas de lípidos holandesas y describimos los hallazgos genéticos, bioquímicos y clínicos. Los primeros hallazgos muestran indicios de una posible mayor prevalencia de pacientes con mutación en el gen APOB respecto a otros territorios. Encontramos hechos históricos que darían una posible explicación a este hecho, apoyando así dicha presunción.(AU)

So far, most cases of hypercholesterolaemia (60-80%) are attributed to pathogenic variants in the LDLR gene. Only 1-5% of cases are caused by variants in the APOB gene, and 0-3% by variants in the PCSK9 gene. There is a large variety in known pathogenic mutations of the LDLR gene, while for those affecting the APOB gene, the highest incidence is p.Arg3527Gln, described predominantly in Central European and North American populations. In the Iberian Peninsula the predominant gene affected is that of the LDL receptor, similar to the rest of the world, with the involvement of the APOB gene being described in individuals from the northwest, and anecdotal in the rest of the territory. A genetics analysis was performed on the population attending the first year of a lipid clinic in southwestern Spain with a 6-point score from the Dutch lipid clinics. The genetic, biochemical and clinical findings are described. The first findings show indications of a possible higher prevalence of patients with mutation in the APOB gene compared to other territories. Historical evidence is presented that could give a possible explanation to this, thus supporting the assumption.(AU)

Genetics and biochemistry of familial hypercholesterolemia in Southwest of the Iberian Peninsula. / Particularidades genéticas y bioquímicas de la hipercolesterolemia familiar en el suroeste de la Península Ibérica.

So far, most cases of hypercholesterolaemia (60-80%) are attributed to pathogenic variants in the LDLR gene. Only 1-5% of cases are caused by variants in the APOB gene, and 0-3% by variants in the PCSK9 gene. There is a large variety in known pathogenic mutations of the LDLR gene, while for those affecting the APOB gene, the highest incidence is p.Arg3527Gln, described predominantly in Central European and North American populations. In the Iberian Peninsula the predominant gene affected is that of the LDL receptor, similar to the rest of the world, with the involvement of the APOB gene being described in individuals from the northwest, and anecdotal in the rest of the territory. A genetics analysis was performed on the population attending the first year of a lipid clinic in southwestern Spain with a 6-point score from the Dutch lipid clinics. The genetic, biochemical and clinical findings are described. The first findings show indications of a possible higher prevalence of patients with mutation in the APOB gene compared to other territories. Historical evidence is presented that could give a possible explanation to this, thus supporting the assumption.

Noonan syndrome: Severe phenotype and PTPN11 mutations / Síndrome de Noonan: fenotipo grave y mutaciones en el gen PTPN11

Introduction and objective: Noonan syndrome (NS) is a genetic disorder characterized by a wide range of distinctive features and health problems. It caused in 50% of cases by missense mutations in PTPN11 gene. It has been postulated that it is possible to predict the disease course based into the impact of mutations on the protein. Patients and methods: We report two cases of severe NS phenotype including hydrops fetalis. PTPN11 gene was studied in germinal cells of both patients by sequencing. Results: Two different mutations (p.Gly503Arg and p.Met504Val) was detected in PTPN11 gene. Discussion: These mutations have been reported previously, and when they were germinal variants, patients presented classic NS, NS with other malignancies and recently, p.Gly503Arg has been also observed in a patient with severe NS and hydrops fetalis, as our cases. Therefore, these observations shade light on that it is not always possibly to determine the genotype-phenotype relation based into the impact of mutations on the protein in NS patients with PTPN11 mutations

Introducción y objetivo: El síndrome de Noonan (SN) es un trastorno genético caracterizado por una amplia gama de signos distintivos y problemas de salud. Está causado en el 50% de los casos por mutaciones missense en el gen PTPN11. Se ha postulado que es posible predecir el curso de la enfermedad en función del impacto de las mutaciones en la proteína. Pacientes y métodos: Presentamos 2 casos de fenotipo severo de SN con hydrops fetalis. En ambos casos se realizó la secuenciación del gen PTPN11 en células germinales. Resultados: Se identificaron 2 mutaciones diferentes en dicho gen (p.Gly503Arg y p.Met504Val). Discusión: Estas mutaciones ya han sido identificadas previamente, y cuando se presentan en línea germinal, los pacientes pueden presentar SN clásico, SN con alteraciones malignas o recientemente, p.Gly503Arg se ha observado en un paciente con SN e hydrops fetalis, como los 2 casos que presentamos. Por tanto, estas observaciones muestran, que en pacientes con SN y mutaciones en el gen PTPN11, no es siempre posible determinar la relación genotipo-fenotipo en función del impacto de la mutación en la proteína

Noonan syndrome: Severe phenotype and PTPN11 mutations.

INTRODUCTION AND OBJECTIVE: Noonan syndrome (NS) is a genetic disorder characterized by a wide range of distinctive features and health problems. It caused in 50% of cases by missense mutations in PTPN11 gene. It has been postulated that it is possible to predict the disease course based into the impact of mutations on the protein. PATIENTS AND METHODS: We report two cases of severe NS phenotype including hydrops fetalis. PTPN11 gene was studied in germinal cells of both patients by sequencing. RESULTS: Two different mutations (p.Gly503Arg and p.Met504Val) was detected in PTPN11 gene. DISCUSSION: These mutations have been reported previously, and when they were germinal variants, patients presented classic NS, NS with other malignancies and recently, p.Gly503Arg has been also observed in a patient with severe NS and hydrops fetalis, as our cases. Therefore, these observations shade light on that it is not always possibly to determine the genotype-phenotype relation based into the impact of mutations on the protein in NS patients with PTPN11 mutations.

Effect of moderate and regular consumption of Cinco Jotas acorn-fed 100% Iberian ham on overall cardiovascular risk: A cohort study.

OBJECTIVE: To evaluate the impact that the moderate and regular consumption of Cinco Jotas acorn-fed 100% Iberian ham has on overall cardiovascular risk, lipid parameters, blood pressure, and weight. METHODS: A longitudinal, analytical, and quasi-experimental clinical study with repeated measures was carried out with 100 randomly selected individuals in primary care. The sample population included men and women (64%) between the ages of 25 and 55 (42.08, SD 9.6) who were not diagnosed with any cardiovascular illness or diabetes, were not undergoing antihypertensive treatment, nor taking lipid-lowering drugs. There were four visits during a 2-week washout period for the first of three phases. Phases 2 and 3 included an 8-week habitual diet phase followed by an 8-week intervention phase when participants consumed 40 g daily of acorn-fed 100% Cinco Jotas Iberian ham. Measurements of cardiovascular risk factors were taken following the SCORE table. These included total cholesterol, high-density lipoproteins cholesterol (HDL-c), low-density lipoproteins cholesterol (LDL-c), triglycerides (TG), and weight. RESULTS: The average vascular risk (SCORE) was 0.20 (SD 0.49) before the consumption phase and 0.18 (SD 0.48) at the end of the study (p > 0.05). An increase in HDL-c of 5 mg/dl was observed while there was a decrease in LDL-c and TG of 10 mg/dl (p < 0.05). There were no differences in total cholesterol levels, blood pressure, or weight; nor were differences observed in average consumption of calories, protein, lipids, carbohydrates, or alcohol (p > 0.05). CONCLUSIONS: The daily consumption of 40 g of Cinco Jotas acorn-fed 100% Iberian ham does not increase the risk of cardiovascular disease and has a favorable impact on lipid levels without affecting blood pressure or weight.

Elevación persistente de troponina en un paciente sin evidencia de cardiopatía isquémica / Persistent increase in troponin levels in a patient without evidence of ischaemic heart disease

No disponible

Utilidad del estudio molecular de la hipercalcemia hipocalciúrica familiar; detección de una nueva mutación genética / Usefulness of molecular study of familial hypocalciuric hypercalcemia; detection of a new genetic mutation

La hipercalcemia hipocalciúrica familiar representa una causa benigna de hipercalcemia de herencia autosómica dominante que no precisa normalmente tratamiento. Presentamos el caso de un varón de 21 años con perfil bioquímico típico de hipercalcemia hipocalciúrica familiar: hipercalcemia leve, niveles normales de PTH e hipocalciuria. Se solicitó el estudio genético del gen CASR, que objetivó en heterocigosis una variante no descrita previamente en la literatura. El padre, con hipercalcemia leve, también era portador de dicha variante. Aunque se trata de una enfermedad sin repercusiones clínicas importantes, es de utilidad realizar la confirmación genética de la hipercalcemia hipocalciúrica familiar para diferenciarla del hiperparatiroidismo primario y para ofrecer un asesoramiento genético adecuado a los pacientes (AU)

Familial hypocalciuric hypercalcemia is a benign cause of hypercalcemia of autosomal dominant inheritance that does not normally require treatment. The case is presented on a 21 year-old male with a typical familial hypocalciuric hypercalcemia biochemical profile: mild hypercalcaemia, normal PTH levels, and hypocalciuria. A genetic study was requested on the CASR gene, which showed a heterozygous variant not previously described in the literature. The father, with mild hypercalcaemia, was also a carrier of this variant. Although it is a disease with no significant clinical repercussions, it is useful to perform genetic confirmation of familial hypocalciuric hypercalcemia to differentiate it from primary hyperparathyroidism and to provide adequate genetic counselling to patients (AU)