Early detection of severe hypertriglyceridemia using teleconsultation in a clinical laboratory setting.

BACKGROUND: Teleconsultation in the context of clinical laboratories is a valuable tool for the early detection of dyslipidemia and prevention of cardiovascular risk. Here, we describe a patient who was referred to the Lipid Unit of the Virgen Macarena Hospital due to an alert for severe hypertriglyceridemia through its teleconsultation program. CASE PRESENTATION: A comprehensive clinical and biochemical study of the patient was carried out, and genetic testing was performed on the patient and his family. The proband and his family showed mild to severe hypertriglyceridemia and various secondary factors, together with a genetic background associated with a triglyceride-raising effect. CONCLUSION: This extensive study has identified a family at high risk of cardiovascular disease and acute pancreatitis. These findings can help maximize lifestyle changes and improve the clinical management of their dyslipidemia.

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

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

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

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

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: what parameters should a basic lipid profile include?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories.

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: What parameters should a basic lipid profile include?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Handling of lipemic samples in the clinical laboratory.

Interferences in the clinical laboratory may lead physicians misinterpret results for some biological analytes. The most common analytical interferences in the clinical laboratory include hemolysis, icterus and lipemia. Lipemia is defined as turbidity in a sample caused by the accumulation of lipoproteins, mainly very-low density lipoproteins (VLDL) and chylomicrons. Several methods are available for the detection of lipemic samples, including the lipemic index, or triglyceride quantification in serum or plasma samples, or mean corpuscular hemoglobin (MCHC) concentration in blood samples. According to the European Directive 98/79/CE, it is the responsibility of clinical laboratories to monitor the presence of interfering substances that may affect the measurement of an analyte. There is an urgent need to standardize interference studies and the way interferences are reported by manufacturers. Several methods are currently available to remove interference from lipemia and enable accurate measurement of biological quantities. The clinical laboratory should establish a protocol for the handling of lipemic samples according to the biological quantity to be tested.

Consensus document for lipid profile determination and reporting in Spanish clinical laboratories. What parameters should be included in a basic lipid profile? / Documento de consenso para la determinación e informe del perfil lipídico en laboratorios clínicos españoles: ¿Qué parámetros debe incluir un perfil lipídico básico?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Role of lipoprotein lipase activity measurement in the diagnosis of familial chylomicronemia syndrome.

BACKGROUND: Activity assays for lipoprotein lipase (LPL) are not standardised for use in clinical settings. OBJECTIVE: This study sought to define and validate a cut-off points based on a ROC curve for the diagnosis of patients with familial chylomicronemia syndrome (FCS). We also evaluated the role of LPL activity in a comprehensive FCS diagnostic workflow. METHODS: A derivation cohort (including an FCS group (n = 9), a multifactorial chylomicronemia syndrome (MCS) group (n = 11)), and an external validation cohort (including an FCS group (n = 5), a MCS group (n = 23) and a normo-triglyceridemic (NTG) group (n = 14)), were studied. FCS patients were previously diagnosed by the presence of biallelic pathogenic genetic variants in the LPL and GPIHBP1 genes. LPL activity was also measured. Clinical and anthropometric data were recorded, and serum lipids and lipoproteins were measured. Sensitivity, specificity and cut-offs for LPL activity were obtained from a ROC curve and externally validated. RESULTS: All post-heparin plasma LPL activity in the FCS patients were below 25.1 mU/mL, that was cut-off with best performance. There was no overlap in the LPL activity distributions between the FCS and MCS groups, conversely to the FCS and NTG groups. CONCLUSION: We conclude that, in addition to genetic testing, LPL activity in subjects with severe hypertriglyceridemia is a reliable criterium in the diagnosis of FCS when using a cut-off of 25.1 mU/mL (25% of the mean LPL activity in the validation MCS group). We do not recommend the NTG patient based cut-off values due to low sensitivity.

SmartLab 2.0 in cardiovascular prevention of atherogenic dyslipidemia. / SmartLab 2.0 en prevención cardiovascular de dislipemia aterogénica.

INTRODUCTION: SmartLab 2.0 is an innovative concept of multidisciplinary collaboration between the clinical laboratory and the diabetes day unit that was born with the aim of identifying patients at high cardiovascular risk who require priority attention, such as patients with atherogenic dyslipidemia, in order to create a cardiovascular prevention strategy. OBJECTIVE: Implementation in the Laboratory Information System (LIS) of an automated biochemical algorithm for the identification of patients with atherogenic dyslipidemia in routine analyses and priority referral to the diabetes day unit. MATERIAL AND METHODS: The algorithm designed in the SIL was: HBA1c>9.3 +TG>150mg/dl +HDLc<40mg/dl +LDL/ApoB<1.3. A comment was inserted alerting the requesting physician of the diagnosis of atherogenic dyslipidemia and priority referral was made from the laboratory to the diabetes day unit in the necessary cases. RESULTS: In the 1-year period, a total of 899 patients with HBA1c>7 and atherogenic dyslipidemia criteria were identified. Of these, 203 patients from primary care with HbA1c>9.3 were referred to the diabetes day hospital. CONCLUSIONS: Reinforcement of cardiovascular prevention is necessary at all levels. The clinical laboratory should play a fundamental role in the diagnosis of dyslipidemias. Early detection of patients at high cardiovascular risk is essential and collaboration between the different clinical units is fundamental to guarantee patient safety.

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.

Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study.

Background: Familial hypercholesterolemia (FH) is clearly underdiagnosed and undertreated. The aim of this present study is to assess the benefits of FH screening through a joint national program implemented between clinical laboratories and lipid units. Methods: All clinical laboratory tests from 1 January 2017 to 31 December 2018 were reviewed, and those with LDL cholesterol (LDL-C) levels >250 mg/dl were identified in subjects >18 years of age of both sexes. Once secondary causes had been ruled out, the treating physician was contacted and advised to refer the patient to an LU to perform the Dutch Lipid Clinic Network score and to request genetic testing if the score was ≥6 points. Next Generation Sequencing was used to analyse the promoter and coding DNA sequences of four genes associated with FH (LDLR, APOB, PCSK9, APOE) and two genes that have a clinical overlap with FH characteristics (LDLRAP1 and LIPA). A polygenic risk score based on 12 variants was also obtained. Results: Of the 3,827,513 patients analyzed in 26 centers, 6,765 had LDL-C levels >250 mg/dl. Having ruled out secondary causes and known cases of FH, 3,015 subjects were included, although only 1,205 treating physicians could be contacted. 635 patients were referred to an LU and genetic testing was requested for 153 of them. This resulted in a finding of sixty-seven pathogenic variants for FH, 66 in the LDLR gene and one in APOB. The polygenic risk score was found higher in those who had no pathogenic variant compared to those with a pathogenic variant. Conclusion: Despite its limitations, systematic collaboration between clinical laboratories and lipid units allows for the identification of large numbers of patients with a phenotypic or genetic diagnosis of FH, which will reduce their vascular risk. This activity should be part of the clinical routine.

Novel APOB nonsense variant related to familial hypobetalipoproteinemia and hepatic steatosis: A case report and review.

Hereditary familial hypobetalipoproteinemia (FHBL) is a syndrome caused by variants in the APOB gene, that cause a defect in the secretion and mobilization of liver lipids to peripheral tissues, associated with the synthesis of truncated ApoB100 apolipoproteins. This condition causes significant reduction in total cholesterol (TC), low-density lipoproteins (LDL), very low-density proteins (VLDL) and serum triglyceride levels, with unchanged high-density lipoprotein (HDL) cholesterol levels. Herein we present the case of a middle-aged woman diagnosed with FHBL and hepatic steatosis, heterozygous for c.4698C>A; (p.Tyr1566Ter) variant in APOB. The variant presented herein showed high expressiveness in the two generations of individuals analyzed and has not yet being described in the medical literature. Early diagnosis and screening for associated metabolic comorbidities such as metabolic fatty liver disease and its subsequent progression to fibrosis are the two main goals in the treatment of this condition, in order to prevent medium to long term potential complications.

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

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

Implantation of a biochemical and genetic screening programme for family hypercholesterolaemia. Collaboration between the clinical laboratory and lipid units: Design of the ARIAN Project. / Implantación de un programa de cribado bioquímico y genético de hipercolesterolemia familiar. Colaboración entre el laboratorio clínico y las unidades de lípidos: diseño del Proyecto ARIAN.

INTRODUCTION AND OBJECTIVE: Familial hypercholesterolaemia (FH) is the most common genetic disorder associated with premature coronary artery disease due to the presence of LDL-C cholesterol increased from birth. It is underdiagnosed and undertreated. The primary objective of the ARIAN project was to determine the number of patients diagnosed with FH after implementing a new screening procedure from the laboratory. MATERIAL AND METHODS: This project was designed as a retrospective analysis by consulting the computer system. We selected from databases serum samples from patients ≥ 18 years with direct or calculated LDL-C>250mg/dL from 1 January 2017 to 31 December 2018. Once secondary causes had been ruled out, the requesting primary care physician was notified that their patient might have FH and to arrange a priority appointment in the lipid unit. All patients with a score of ≥ 6 points according to the Dutch Lipid Clinic Criteria were proposed for a genetic study RESULTS: By December 30th, 2020, 24 centres out of the initial 55 had submitted results. The number of patients analysed up to that point was 3,266,341, which represents 34% of the population served in those health areas (9,727,434). CONCLUSIONS: The identification of new subjects with FH through this new strategy from the laboratory and their referral to lipid units should increase the number of patients treated in lipid units and initiate familial cascade screening.

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.

Prevalence of severe hypercholesterolemia observed in different hospitals in Andalusia and Ceuta. / Prevalencia de hipercolesterolemias severas observadas en los distintos hospitales de Andalucía y Ceuta.

Severe hypercholesterolaemia is a major cardiovascular risk factor. Early detection and treatment can reduce the incidence of cardiovascular disease. Given the high prevalence of hypercholesterolaemia in Andalusia, the development of a screening strategy for its detection in Primary Care may be an efficient measure. OBJECTIVE: To identify patients in Primary Care with severe hypercholesterolaemia that may increase their cardiovascular risk by reviewing LDL-cholesterol results in computerised laboratory systems. MATERIAL AND METHODS: Observational, retrospective, multi-centre study in 16 hospitals in Andalusia and Ceuta. Anonymous analytical data were acquired from the different laboratory computer systems for the year 2018, and exclusively from Macarena Hospital for the year 2019. RESULTS: From a total of 1,969,035 determinations on≥18 years old, 2,791 patients (0.14%) were detected with LDL-cholesterol>250mg/dl and from a total of 2.327.211 determinations studied in children under 18 years old, 3,804 patients (0.16%) were detected with LDL-cholesterol>135mg/dL. The highest incidence of possible genetic hypercholesterolaemia in adults corresponded to the province of Seville with 23.6 cases/1,000 determinations, while in minors, the highest incidence corresponded to the province of Cadiz with 75 possible cases/1,000 determinations. A geographical triangle of greater prevalence is observed between the provinces of Seville, Huelva and Cadiz. CONCLUSIONS: The development of a screening strategy using a computerised review of LDL-cholesterol in Primary Care detects a large number of subjects with severe hypercholesterolaemia that could benefit from an early intervention.

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.

Removing Lipemia in Serum/Plasma Samples: A Multicenter Study.

BACKGROUND: Lipemia, a significant source of analytical errors in clinical laboratory settings, should be removed prior to measuring biochemical parameters. We investigated whether lipemia in serum/plasma samples can be removed using a method that is easier and more practicable than ultracentrifugation, the current reference method. METHODS: Seven hospital laboratories in Spain participated in this study. We first compared the effectiveness of ultracentrifugation (108,200×g) and high-speed centrifugation (10,000×g for 15 minutes) in removing lipemia. Second, we compared high-speed centrifugation with two liquid-liquid extraction methods-LipoClear (StatSpin, Norwood, USA), and 1,1,2-trichlorotrifluoroethane (Merck, Darmstadt, Germany). We assessed 14 biochemical parameters: serum/plasma concentrations of sodium ion, potassium ion, chloride ion, glucose, total protein, albumin, creatinine, urea, alkaline phosphatase, gamma-glutamyl transferase, alanine aminotransferase, aspartate-aminotransferase, calcium, and bilirubin. We analyzed whether the differences between lipemia removal methods exceeded the limit for clinically significant interference (LCSI). RESULTS: When ultracentrifugation and high-speed centrifugation were compared, no parameter had a difference that exceeded the LCSI. When high-speed centrifugation was compared with the two liquid-liquid extraction methods, we found differences exceeding the LCSI in protein, calcium, and aspartate aminotransferase in the comparison with 1,1,2-trichlorotrifluoroethane, and in protein, albumin, and calcium in the comparison with LipoClear. Differences in other parameters did not exceed the LCSI. CONCLUSIONS: High-speed centrifugation (10,000×g for 15 minutes) can be used instead of ultracentrifugation to remove lipemia in serum/plasma samples. LipoClear and 1,1,2-trichlorotrifluoroethane are unsuitable as they interfere with the measurement of certain parameters.