Lansoprazole Increases Inorganic Pyrophosphate in Patients with Pseudoxanthoma Elasticum: A Double-Blind, Randomized, Placebo-Controlled Crossover Trial.

Pseudoxanthoma elasticum (PXE) is characterized by low levels of inorganic pyrophosphate (PPi) and a high activity of tissue-nonspecific alkaline phosphatase (TNAP). Lansoprazole is a partial inhibitor of TNAP. The aim was to investigate whether lansoprazole increases plasma PPi levels in subjects with PXE. We conducted a 2 × 2 randomized, double-blind, placebo-controlled crossover trial in patients with PXE. Patients were allocated 30 mg/day of lansoprazole or a placebo in two sequences of 8 weeks. The primary outcome was the differences in plasma PPi levels between the placebo and lansoprazole phases. 29 patients were included in the study. There were eight drop-outs due to the pandemic lockdown after the first visit and one due to gastric intolerance, so twenty patients completed the trial. A generalized linear mixed model was used to evaluate the effect of lansoprazole. Overall, lansoprazole increased plasma PPi levels from 0.34 ± 0.10 µM to 0.41 ± 0.16 µM (p = 0.0302), with no statistically significant changes in TNAP activity. There were no important adverse events. 30 mg/day of lansoprazole was able to significantly increase plasma PPi in patients with PXE; despite this, the study should be replicated with a large number of participants in a multicenter trial, with a clinical end point as the primary outcome.

Evaluation of the chylomicron-TG to VLDL-TG ratio for type I hyperlipoproteinemia diagnostic.

BACKGROUND: The aim of this study is to confirm the diagnostic performance of the Chylomicron to very low-density lipoproteins triglycerides (CM/VLDL-TG) ratio, the triglycerides to cholesterol ratio (TG/TC) and a dichotomic rule including the tryglycerides to apolipoprotein B (TG/APOB) ratio for the presence of Type I hyperlipoproteinemia (HPLI) in patients with severe hypertriglyceridemia (sHTG) that were at high risk for familial chylomicronemia syndrome (FCS). METHODS: Two cohorts (derivation and validation) of patients with sHTG were included in the study. Anthropometric, clinical, biochemical and genetic data were obtained. The CM/VLDL-TG, TG/TC and TG/APOB ratios were calculated. Finally, a diagnostic performance study was developed to establish sensitivity, specificity and cut-offs by a ROC curve analysis in the derivation cohort as well as agreement and predictive values in the validation cohort. RESULTS: Patients with FCS in both cohorts showed an earlier presence in pancreatitis, greater number of acute pancreatitis episodes and lower BMI. FCS patients also showed higher ratios of CM/VLDL-TG, TG/TC and TG/APOB ratios, whereas their HDL-C, LDL-C and APOB levels were lower than in non-FCS patients. Sensitivity and agreement were low for both the TG/TC and TG/APOB ratios, although predictive values were good. The CM/VLDL-TG ratio showed greatest sensitivity, specificity, agreement and predictive values for cut-off of 3.8 and 4.5. CONCLUSIONS: Our results suggest that in subjects at high risk of FCS a total serum TG/TC ratio or TG/APOB ratio are feasible to initially screen for HLPI; however, a CM/VLDL-TG ratio ≥4.5 is a better diagnostic criterion for HPLI.

Evidence for increased chylomicron remnants in rheumatoid arthritis.

BACKGROUND: Levels of apolipoprotein (apo) B48 may be increased in conditions associated with systemic inflammation and increased cardiovascular disease (CVD) risk such as rheumatoid arthritis (RA). We aimed to evaluate apo B48 levels in patients with RA in relation to subclinical atherosclerosis. METHODS: Patients with RA (without CVD) and controls without RA but with high CVD risk (based on the presence of diabetes mellitus or a history of CVD) and healthy controls were included in this cross-sectional study. Carotid intima-media thickness (cIMT) was measured as a surrogate for vascular damage. RESULTS: In total, 312 patients with RA, 65 controls with high CVD risk and 36 healthy controls were included. Patients with RA had the highest mean apo B48 (10.00 ± 6.65 mg/L) compared to controls with high CVD risk and healthy controls (8.37 ± 5.16 and 5.22 ± 2.46, P < .001). Triglycerides levels were comparable with controls. In RA, apo B48 correlated positively with triglycerides (r = .645; P < .001) but not with cIMT. However, in RA subjects not using lipid or blood pressure lowering medication, a weak correlation was found with cIMT (r = .157; P = .014). RA patients in the highest apo B48 tertile were more often rheumatoid factor positive and anti-CCP positive compared to the lowest tertile. CONCLUSION: Rheumatoid arthritis patients have higher levels of apo B48 compared to controls with high CVD risk and healthy controls, with normal levels of triglycerides. This accumulation of atherogenic chylomicron remnants may contribute to the elevated CVD risk in RA patients.

Approach to the management of pregnancy in patients with pseudoxanthoma elasticum: a review.

Management of pregnancy in patients with rare diseases is often guided by incomplete knowledge because of a lack of high-quality case control studies or single-centre experience. Pseudoxanthoma elasticum (PXE) is an autosomal recessive metabolic disorder that results in calcification of elastic fibres of the skin, retina, and arteries, leading to skin lesions, eventual central visual loss, and potential arterial insufficiency in most patients. It is due to mutations in ABCC6, which encodes the eponymous membrane transport protein. We review the literature on pregnancy in PXE, including the effects of the diseases on pregnancy and its complications, the effect of PXE on the foetus, and the effects of pregnancy on PXE, and conclude that in the majority of pregnancies in women with PXE, the outcome for mother, baby, and the disease is uneventful. We also provide recommendations for managing pregnancy in PXE.

Apolipoprotein C-III, familial chylomicronemia syndrome, and olezarsen.

Reducing the synthesis of apoC-III reduces fasting triglycerides in individuals lacking lipoprotein lipase activity. Recently, Stroes et al.1 published a phase 3 trial on the effects of olezarsen, a third-generation antisense oligonucleotide that blocks apoC-III mRNA, on triglycerides and risk of acute pancreatitis.

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.

Differences in cardiovascular risk and health-related quality of life in COPD patients according to clinical phenotype.

Chronic obstructive pulmonary disease (COPD) has a high prevalence and a major impact on health-related quality of life (HRQL). COPD exacerbations are an important cause of morbidity and mortality, affecting cardiovascular risk, and are associated with poorer health status. The aim of this study was to assess the association between cardiovascular risk (CVR) and HRQL, according to exacerbator or non-exacerbator phenotype. We undertook a cross-sectional, observational, descriptive study of 107 patients with COPD. Patients with two or more moderate exacerbations or one severe exacerbation in the previous year were considered as exacerbators. The CVR was calculated with the Framingham scale and SCORE (Systematic Coronary Risk Evaluation) and the HRQL was assessed with the generic questionnaire Short Form-36 Health Survey (SF-36), the St George Respiratory Questionnaire (SGRQ) and the COPD Assessment Test (CAT). Statistical analysis was done with SPSS version 26.0 for Windows. The SF-36 and the SGRQ showed lower values for the exacerbator phenotype, indicating a poorer quality of life. The CAT questionnaire showed values above 10 for the exacerbator phenotype, and lower values in the non-exacerbator group. After categorizing the sample according to their median age (65 years), we found a greater deterioration in HRQL in patients under 65 years of age according to the SF-36, the SGRQ and the CAT. We also detected differences in HRQL between non-exacerbator patients with a high CVR according to the Framingham (≥ 20%) and SCORE (≥ 5%) scales compared to those without this risk. A tendency towards worse HRQL was observed in non-exacerbator patients with a high CVR, which was statistically significant for the SGRQ impact domain on the SCORE scale. The CAT also showed a worse quality of life in non-exacerbator patients with a high CVR, which was significant in the Framingham model (Framingham high risk 8.41 vs non-high risk 6.05, p < 0.01). These differences were not observed in exacerbator patients. Our findings confirm that a high CVR influences HRQL in patients with COPD, especially in non-exacerbator patients with a high CVR, measured according to the SGRQ and the CAT.

Validation of the IberScore model in a primary care population.

BACKGROUND: This study aimed to validate the IberScore cardiovascular risk model in a population attended in the primary care setting. METHODS: A cohort of patients with no history of cardiovascular disease visited in a primary care center during the years 2008 and/or 2009 and followed up until 2018 was selected. Cardiovascular risk was calculated with the IberScore formula for all the subjects of the cohort and the model was calibrated, graphically represented by risk deciles the proportion of expected events and proportion of observed events at 10-year follow-up, stratified by sex. The area under the ROC curve was calculated to assess the discrimination of the model. RESULTS: A total of 10,085 patients visited during the years 2008 and/or 2009 were included in the study. Men showed a mean 10-year risk of suffering a fatal or non-fatal cardiovascular events according to IberScore of 17.07% (SD 20.13), with a mean estimated vascular age of more than 4 years higher than the biological age; while women had a mean 10-year risk of 7.91% (SD 9.03), with an estimated vascular age of more than 2 years above the biological age. The area under the ROC curve showed a discrimination index of the model of 0.86 (95% CI 0.84-0.88) in men and 0.82 (95% CI 0.79-0.85) in women. CONCLUSION: IberScore model discriminates well in the population attended in primary care but the model overestimates the risk.

Clinical characterization and detection of subclinical atherosclerosis in subjects with extreme hyperalphalipoproteinemia. / Caracterización clínica y detección de arteriosclerosis subclínica en sujetos con hiperalfalipoproteinemia extrema.

INTRODUCTION AND OBJECTIVES: The association between HDL cholesterol (HDL-C) levels and death from cardiovascular disease follows a U-shaped pattern, increasing at the extremes. The objective of the study was to characterize a sample of subjects with extreme hyperalphalipoproteinemia (HAE). MATERIAL AND METHODS: 53 cases with HAE were recruited, 24 women (HDL-C>135mg/ dL) and 29 men (HDL-C>116mg/ dL). A detailed medical history was taken and questionnaires on adherence to the Mediterranean diet and physical activity were collected. Carotid ultrasounds were performed to detect the presence of suclinical atherosclerosis. RESULTS: The most prevalent cardiovascular risk factor (CVRF) was dyslipidemia (64%) with no significant differences between men and women, unlike hypertension (21% in women, versus 55% in men, p=0.01) and others CVRF, for example, diabetes. 7% of the series had previous cardiovascular disease, women had higher LDL cholesterol (p=0.002) and HDL-C than men (without significant differences). Plaque was detected in 53% of cases, being more prevalent in men. Patients with plaque were older, drank more alcohol and smoked more (p<0.05). CONCLUSIONS: Men had a higher prevalence of CVRF than women, except for dyslipidemia. Subclinical atherosclerosis occurred in more than half of the series. Age, alcohol consumption and smoking were independently associated with the presence of plaque, however, our data do not show a significant influence of HDL-C levels.

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.

A case of hypocholesterolemia under study. / Un caso de hipocolesterolemia a estudio.

Primary hypocholesterolemia (or hypobetalipoproteinemia) is a rare disorder of lipoprotein metabolism that may be due to a polygenic predisposition or a monogenic disease. Among these, it is possible to differentiate between symptomatic and asymptomatic forms, in which, in the absence of secondary causes, the initial clinical suspicion is plasma ApoB levels below the 5th percentile of the distribution by age and sex. Here we describe the differential diagnosis of a case of asymptomatic hypocholesterolemia. We studied proband's clinical data, the lipid profile of the proband and her relatives and the clinical data of the family relevant to carry out the differential diagnosis. We performed a genetic study as the diagnostic test. The information obtained from the differential diagnosis suggested a heterozygous hypobetalipoproteinemia due to PCSK9 loss-of-function variants. The diagnostic test revealed, in the proband, the presence of a heterozygous PCSK9 frame-shift variant of a maternal origin. Plasma levels of LDL cholesterol and PCSK9 of the patient and her relatives were compatible with the segregation of the variant revealed. In conclusion, the diagnostic test performed confirmed the suspected diagnosis of the proband as asymptomatic familial hypobetalipoproteinemia due to a loss-of-function variant in the PCSK9 gene.

Symptoms and impacts of familial chylomicronemia syndrome: a qualitative study of the patient experience.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare, hereditary, metabolic disorder. FCS causes high levels of triglycerides in the blood, which can lead to abdominal pain, xanthomas, and acute pancreatitis (AP). Volanesorsen, along with adherence to a very low-fat diet is used to reduce triglyceride levels in individuals with FCS. We aimed to understand the symptoms of FCS and their impact on health-related quality of life (HRQoL). METHODS: Interviews were conducted with individuals with genetically confirmed FCS in the UK and Spain, some of whom had been treated with volanesorsen. Interview guides were developed with input from a patient advocacy group to explore the symptoms, impacts and management of FCS. Interviews were conducted by telephone and were recorded and transcribed. Data were analyzed using thematic analysis and saturation was recorded. RESULTS: Seventeen interviews were conducted with individuals with FCS (aged 27-68 years), thirteen of whom were currently/previously treated with volanesorsen. Episodes of AP were the most impactful reported symptom, resulting in severe abdominal pain, nausea, vomiting, fever, bloating and appetite loss. Other symptoms and functional issues included abdominal pain, gastrointestinal symptoms, impaired cognitive function and fatigue. These had an impact on work, social activities, relationships and psychological wellbeing. These symptoms and impacts were illustrated in a conceptual model, including management strategies. The challenges of managing a low-fat diet and experience with volanesorsen were discussed. CONCLUSION: Individuals with FCS experience a range of interrelated symptoms and functional limitations which impact their broader HRQoL. Treatments which alleviate symptoms and reduce the incidence of AP episodes have the potential to improve the HRQoL of these individuals.

Doctors' perception of red wine consumption and cardiovascular health. / Percepción de los médicos frente al consumo de vino tinto y la salud cardiovascular.

INTRODUCTION: The consumption of red wine has historically been associated with a reduction in cardiovascular risk, with sometimes controversial scientific evidence. METHOD: A survey was carried out via whatsapp dated 09/01/22 to a cohort of doctors from the province of Malaga, asking about possible healthy red wine consumption habits, differentiating: never, 3-4 glasses per week, 5 -6 weekly drinks and one daily drink. RESULTS: A total of 184 physicians answered, with a mean age of 35 years ± 11.1, of which 84 (45.6%) were women, distributed in different specialties, the majority being internal medicine with 52 (28.2%). The most frequently chosen option was D (59.2%), followed by A (21.2%), C (14.7%) and B (5%). CONCLUSIONS: More than half of the doctors surveyed recommended zero consumption, and only 20% indicated that a daily drink could be healthy in non-drinkers.

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.

Subclinical atherosclerosis burden in non-diabetic hypertensives treated in primary care center: the IMTABI study.

BACKGROUND: Identifying patients at high risk of cardiovascular disease in primary prevention is a challenging task. This study aimed at detecting subclinical atherosclerosis burden in non-diabetic hypertensive patients in a primary care centre. METHODS: Clinical, anthropometric and analytical data were collected from patients with hypertension who were free from clinical vascular disease and diabetes. The cardiovascular risk was assessed using the SCORE system. Subclinical atherosclerosis burden was assessed by carotid ultrasonography (intima-medial thickness [IMT] and plaque) and measurement of the ankle-brachial index (ABI). RESULTS: Out of 140 patients, 59 (42%) have carotid plaque, 32 (23%) have IMT higher than 75% and 12 (9%) have an ABI < 0.9. Total atherosclerosis burden was present in 91 (65%) of the subjects. Consequently, 59 (42%) patients were re-classified into the very high-risk category. In multivariate analyses, smoking, creatinine levels and duration of hypertension were associated with atherosclerosis burden. In contrast, only smoking and age were associated with the presence of carotid plaque. Almost 90% of patients were treated with hypotensive drugs, half of them combined several drugs and 60% were well-controlled. Only 30% received statins in monotherapy and only less than 20% had an LDL cholesterol < 100 mg/dL. CONCLUSIONS: In non-diabetic hypertensive patients managed at a primary care centre, 4 out of 10 had subclinical atherosclerosis burden and were re-classified into the very high- risk category. There was clear undertreatment with lipid-lowering drugs of most LDL cholesterol inappropriate levels, according to current clinical guidelines.

Impact of physician's perception about LDL cholesterol control in clinical practice when treating patients in Spain.

BACKGROUND AND AIMS: We aimed to understand the impact of physicians' perception about LDL-cholesterol (LDLc) control on the management of patients with dyslipidemia in Spain. METHODS: We performed a cross-sectional and multicenter study, in which 435 healthcare professionals participated in face-to-face meetings, collecting qualitative and quantitative information related to hypercholesterolemia management. Additionally, aggregated anonymized data of the last 10 patients with hypercholesterolemia attended by each physician were collected. RESULTS: A total of 4,010 patients (8%, 13%, 16% and 61% with low, moderate, high, and very high cardiovascular [CV] risk) were included. Physicians' perception was that 62% of their patients attained LDLc goals (66%, 63%, 61% and 56%, for low, moderate, high and very high CV risk, respectively). However, when looking into the data only 31% (vs 62% p<0.01) of patients attained the LDLc goals (47%, 36%, 22% and 25%, respectively). Overall, 33% of patients were taking high intensity statins, 32% statin/ezetimibe, 21% low/moderate intensity statins and 4% PCSK9 inhibitors. These numbers were 38%, 45%, 8% and 6% for very high risk patients and 44%, 21%, 21% and 4% for high CV risk patients. In 32% of patients, a change in lipid lowering therapy was performed after the visit, mainly combining statins/ezetimibe (55%). CONCLUSIONS: In Spain, most patients with dyslipidemia do not achieve the recommended LDLc goals because of an insufficient intensification of lipid lowering therapy. On the one hand, this is in part due to physicians misperception on preventive LDLc control and the need for repeated advice to patient, and, on the other, to the lack of patient adherence.

Hypercholesterolaemia control in Spain: The same situation with different regional realities. / Control de la hipercolesterolemia en España: una misma situación con diferentes realidades autonómicas.

INTRODUCTION AND OBJECTIVE: The cardiovascular prevention strategy by autonomous communities can be variable since the competences in health are transferred. The objective of the study was to determine the degree of dyslipidaemia control and the lipid-lowering pharmacological therapy used in patients at high/very high cardiovascular risk (CVR) by autonomous communities. METHODS: Observational, cross-sectional, descriptive study based on a consensus methodology. Information on the clinical practice of 145 health areas belonging to 17 Spanish autonomous communities was collected through face-to-face meetings and questionnaires administered to the 435 participating physicians. Furthermore, aggregate non-identifiable data were compiled from 10 consecutive dyslipidaemic patients that each participant had recently visited. RESULTS: Of the 4010 patients collected, 649 (16%) had high and 2458 (61%) very high CVR. The distribution of the 3107 high/very high CVR patients was balanced across regions, but there were inter-regional differences (P<.0001) in the achievement of target LDL-C <70 and <55mg/dL, respectively. High-intensity statins in monotherapy or in combination with ezetimibe and/or PCSK9 inhibitors were used in 44, 21 and 4% of high CVR patients, while in those at very high CVR it rose to 38, 45 and 6%, respectively. The use of these lipid-lowering therapies at national level was significantly different between regions (P=.0079). CONCLUSIONS: Even though the distribution of patients at high/very high CVR was similar between autonomous communities, inter-territorial differences were identified in the degree of achievement of LDL cholesterol therapeutic goal and use of lipid-lowering therapy.

Exploring the value of apoB48 as a marker for atherosclerosis in clinical practice.

BACKGROUND: Postprandial accumulation of atherogenic remnants has been described in patients with type 2 diabetes mellitus (T2DM), familial combined hyperlipidaemia (FCH), familial hypercholesterolaemia (FH) and coronary artery disease (CAD). Scarce data are available on fasting plasma apolipoprotein (apo) B48 levels in relation to these conditions and atherosclerosis. DESIGN: Treated patients with FCH (18), FH (20), T2DM (26), CAD (65), T2DM with CAD (T2DM/CAD) (28) and 33 healthy controls were included. Intima-media thickness (IMT) measurements were carried out to investigate subclinical atherosclerosis. RESULTS: LDL-C and total apoB were lowest in patients with T2DM/CAD owing to the more frequent use of lipid-lowering medication. Fasting plasma apoB48 was elevated in patients with FCH (11·38 ± 1·50 mg/L) and T2DM/CAD (9·65 ± 1·14 mg/L) compared with the other groups (anova, P < 0·01). CAD patients (8·09 ± 0·57 mg/L) had higher apoB48 levels than controls (5·74 ± 0·55 mg/L) and FH patients (5·40 ± 0·51 mg/L) (P = 0·02). IMT was highest in subjects with T2DM/CAD (0·77 ± 0·03 mm) (P < 0·01). The lowest IMT was measured in controls (0·56 ± 0·02 mm) and FCH patients (0·60 ± 0·03 mm). In the total group, the best association for apoB48 was found with fasting triglyceride (Pearson's r = 0·72, P < 0·001). In the subjects not using statins (n = 74), the best correlation was found with IMT (r = 0·52; P < 0·001), whereas total apoB was not associated with IMT (r = 0·20, P = 0·12). CONCLUSIONS: ApoB48 concentrations are highest in patients with FCH and in atherosclerotic subjects with T2DM. In patients not using statins, the surrogate atherosclerosis marker IMT correlates best with apoB48, suggesting that fasting apoB48 may help to detect subjects at risk.

Triglyceride levels and apolipoprotein E polymorphism in patients with acute pancreatitis.

BACKGROUND: Hypertriglyceridemia is an unusual cause of acute pancreatitis and sometimes considered to be an epiphenomenon. This study aimed to investigate the clinical and analytical features and the APOE genotypes in patients with acute pancreatitis and severe hypertriglyceridemia. METHODS: We undertook a one-year, prospective study of patients with acute pancreatitis whose first laboratory analysis on admission to the emergency department included measurement of serum triglycerides. The APOE genotype was determined and the patients answered an established questionnaire within the first 24 hours concerning their alcohol consumption, the presence of co-morbidities and any medications being taken. The patients' progression, etiological diagnosis, hospital stay and clinical and radiological severity were all recorded. RESULTS: Hypertriglyceridemia was responsible for 7 of 133 cases of pancreatitis (5%); the remaining cases were of biliary (53%), idiopathic (26%), alcoholic (11%) or other (5%) origin. Compared with these remaining cases, the patients with hypertriglyceridemia were significantly younger, had more relapses, and more often had diabetes mellitus. They usually consumed alcohol or consumed it excessively on the days before admission. Also, the ε4 allele of the APOE gene was more common in this group (P<0.05). CONCLUSION: One of 20 episodes of acute pancreatitis is caused by hypertriglyceridemia and it is linked to genetic (ε4 allele) and comorbid factors such as diabetes and, especially, alcohol consumption.

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.