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.

Influence of high cardiovascular risk in asymptomatic people on the duration and cost of sick leave: results of the ICARIA study.

AIMS: We investigated the potential influence of a moderate-to-high cardiovascular (CV) risk (CVR) (defined as a Systematic COronary Risk Evaluation model, or SCORE ≥ 4%), in the absence of an established CV disease, on the duration and cost of CV and non-CV sick leave (SL) resulting from common and occupational accidents or diseases. METHODS AND RESULTS: We conducted a prospective cohort study on 690 135 workers with a 1-year follow-up and examined CV- and non-CV-related SL episodes. To obtain baseline values, CVR factors were initially assessed at the beginning of the year during routine medical examination. The CVR was calculated with the SCORE charts for all subjects. Moderate-to-high CVR was defined as SCORE ≥ 4%. A baseline SCORE ≥ 4% was associated with a higher risk for long-term CV and non-CV SL, as revealed by follow-up assessment. This translated into an increased cost, estimated at €5 801 464.18 per year. Furthermore, pharmacological treatment for hypertension or hyperlipidaemia was significantly associated with longer SL duration. CONCLUSION: Moderate-to-high CVR in asymptomatic subjects was significantly associated with the duration and cost of CV and non-CV SL. These results constitute the first body of evidence that the SCORE charts can be used to identify people with a non-established CV disease, which might ultimately translate into more lost workdays and therefore increased cost for society.

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.

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.

Update and validation of the lifetime cardiovascular risk in Spain: IBERLIFERISK2. / Actualización y validación del riesgo cardiovascular de por vida en España: IBERLIFERISK2.

INTRODUCTION: The function to estimate lifetime cardiovascular risk -IBERLIFERISK- in Spanish working population, obtained a satisfactory discrimination; however, there was a slight overestimation of the risk in men and an underestimation of the risk in women. OBJECTIVE: To recalibrate the current lifetime risk equation after extending the follow-up by 3 years. METHODS: Retrospective cohort study. 762.058 workers who underwent an occupational health examination between 2004 and 2007 were included. All episodes of temporary sickness and cardiovascular mortality up to December 2017 were evaluated. Regression models were combined to take into account the presence of competing risks in estimating cardiovascular risk in the derivation cohort. Calibration was performed by graphically representing the proportion of expected and observed events at 10 years of follow-up in the validation cohort, stratifying by risk deciles and calculating the Spiegelhalter Z statistic. Discrimination was evaluated graphically using the Receiver Operating Curve (ROC) and calculating Harrell's C index. RESULTS: The mean age was 35.48 years (SD 10.56). 71.14% were men. Harrell's C index was 0.78 (95% CI 0.76-0.79) in men and 0.73 (95% CI 0.69-0.77) in women. In general, there was a slight degree of underestimation in women and overestimation in men in the last decile of risk, although the Spiegelhalter Z statistic was not statistically significant in both sexes (p>0.05). CONCLUSIONS: The updated model continues to discriminate satisfactorily, although the model's calibration has not substantially improved with the new update.

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.

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.

Relationship beetween Primary and Hospital Care in cardiovascular prevention and treatment of dyslipidemias. Derivation algorithm. Discharge criteria. / Relación entre Atención Primaria y Hospitalaria en la prevención cardiovascular y tratamiento de las dislipidemias. Algoritmo de derivación. Criterios de alta.

Effective cardiovascular prevention requires taking advantage of all opportunities for patient contact with the Health Services in order to detect risk factors (CVRF) and global cardiovascular risk stratification (CVR). This particularly involves the Primary Care (PC) services, which must be coordinated with the Hospital Care (HC) in order to make all health resources available to the population. In addition, it is necessary to take into account the contribution of Occupational Health and Pharmacy services. There are hopeful signs as regards the possibility of overcoming the barriers that limit the necessary exchange of information between PC and HC professionals, as a basis for adequate coordination between both levels of care. This includes the implementation of referral and discharge algorithms (in this review this means those related to dyslipidaemias) accepted by professionals at both levels, and currently facilitated by the availability of new corporate tools (mobile, email, virtual consultations). The challenge lies in seizing the opportunity they offer to make their implementation effective.

Prevalence of familial hypercholesterolemia phenotype and ten-year risk of cardiovascular events in a working population in primary prevention: The ICARIA study.

BACKGROUND AND AIMS: We aimed to assess the prevalence of familial hypercholesterolaemia (FH) and to determine the incidence of cardiovascular events during a 10-year follow up in individuals with FH, compared to unaffected individuals in a working, middle-aged/young population. METHODS AND RESULTS: 576,724 active workers (36 ± 10 years-old, 70% men) without cardiovascular disease were given regular health check-ups and followed for a median of 8.5 years (i.e., 4,123,927 person-years). The FH phenotype was defined according to validated low-density lipoprotein-cholesterol thresholds, adjusted for age and sex. The primary outcome was a first cardiovascular event, whether fatal or non-fatal. We found that 707 workers (0.12% or 1 in 816 individuals) met the criteria for a heterozygous FH phenotype. During the follow-up, cardiovascular events occurred in 23 of 707 (3.25%) subjects with the FH phenotype and in 3297 of 576,017 (0.57%) subjects without the FH phenotype (p<0.001). The hazard ratio (HR, assessed with a Cox regression model) for the primary outcome was 5.7 (99% CI 3.33-9.78), before adjustments, and 4.7 (99% CI 2.62-8.58) after adjusting for sex, age, smoking, blood pressure, and diabetes. The HRs were significant for both men and women, but the magnitude of the effect was greater for men than for women. CONCLUSIONS: Our findings confirmed the high incidence of cardiovascular disease in individuals with untreated FH. We showed that regular health check-ups in an active, and mostly young, working population could contribute to the early identification of FH. Therefore, this approach may provide an opportunity for early treatment.

Cutaneous and Vascular Deposits of 18F-NaF by PET/CT in the Follow-Up of Patients with Pseudoxanthoma Elasticum.

Active microcalcification of elastic fibers is a hallmark of pseudoxanthoma elasticum and it can be measured with the assessment of deposition of 18F-NaF using a PET/CT scan at the skin and vascular levels. It is not known whether this deposition changes over time in absence of specific therapy. We repeated in two years a PET/CT scan using 18F-NaF as a radiopharmaceutical in patients with the disease and compared the deposition at skin and vessel. Furthermore, calcium score values at the vessel wall were also assessed. Main results indicate in the vessel walls that calcification progressed in each patient; by contrast, the active microcalcification, measured and target-to-background ratio showed reduced active deposition. By contrast, at skin levels (neck and axillae) the uptake of the pharmaceutical remains unchanged. In conclusion, because calcification in the arterial wall is not specific for pseudoxanthoma elasticum condition, the measurement of the deposition of 18F-NaF in the neck might be potentially used as a surrogate marker in future trials for the disease.

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study.

BACKGROUND: Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. METHODS: A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG > or = 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. RESULTS: We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-epsilon4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG. CONCLUSION: Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the epsilon4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.

[Effectiveness of a preventive intervention strategy based on structured telephone interviews in a working population with a moderate to high cardiovascular risk]. / Efectividad de una estrategia de intervención preventiva, basada en entrevistas telefónicas estructuradas, en una población laboral con riesgo cardiovascular moderado/alto.

OBJECTIVE: This study assesses the effectiveness of a structured telephone survey on cardiovascular prevention, in modifying lifestyle, on cardiovascular risk parameters, percentage of smoking cessation and overall cardiovascular risk (CVR). DESIGN: Quasi-experimental study of preventive intervention. SETTING: Ibermutuamur (Spanish Accident and Health Insurance Company). Centres established throughout Spain. PARTICIPANTS: A total of 4,792 workers with moderate/high cardiovascular risk who had agreed to be contacted by phone. Subjects with a previous diagnosis of cardiovascular disease and those receiving treatment for hypertension, hypercholesterolemia or diabetes were excluded. INTERVENTION: A final total of 3,085 workers were contacted and were followed up by telephone surveys on the first, fourth and eighth month after the initial check up (CU) in order to emphasise cardiovascular health advice (Group A); we failed to contact 1,707 workers, who only attended the baseline and one year CUs (Group B). PRINCIPAL OUTCOMES: CUs included medical records and physical examination, with two blood pressure measurements, Body Mass Index (BMI), and biochemical parameters. Cardiovascular risk was stratified following the European cardiovascular SCORE. Individuals with a relative risk higher than 4 were also considered as high-risk. All workers were informed about their cardiovascular risk profile (CVRF) and healthy cardiovascular lifestyle measures. They were also given a letter for their General Practitioner (GP) to inform them on the worker's cardiovascular risk level. RESULTS: A total of 71.5% of the workers were over 45 years, 95.0% males, 76.6% manual workers ("Blue Collar") and 69.7% smokers. Both groups showed improvement in lipid parameters, blood pressure, smoking cessation and overall cardiovascular risk in the second CU. There were significant differences in favour of Group A as regards blood pressure, lipids (except HDL cholesterol), BMI, glycaemia, smoking cessation (A: 23.5%/B: 19.44%, P=0.001) and CVR stratum improvement (A: 46.6%/B: 37.7%, P=0.0001). The large majority (85%) of workers read preventive recommendations; 33% knew their risk level and 73% knew their CVRF. 52.9% gave the letter to the GP, which led them to start therapies on diet (47%), hypertension (19.5%), dyslipidaemia (16.7%), diabetes (4.4%) and smoking (2.9%) and no changes were made in 36.5% of cases. CONCLUSIONS: The results of this study suggests that cardiovascular prevention strategy based on structured telephone surveys on high/moderate CVR subjects to promote lifestyle changes could be effective at reducing CVR. A clinical trial is required for confirmation. Sending information on CVRF following routine medial CUs and Primary Care involvement, could contribute to the positive changes observed.

COVID-19 and Sick Leave: An Analysis of the Ibermutua Cohort of Over 1,651,305 Spanish Workers in the First Trimester of 2020.

Objectives: The worldwide SARS-COV2 pandemic has impacted the health of workers and companies. The aim is to quantify it according to sick leave. Methods: Using ICD-9 codes, we analyzed Ibermutua records of all sick leaves during the first trimester of 2020, compared to during the same months of 2017, 2018, and 2019. We stratified the analysis by causes, patient sex, activity sectors, and regional data. All sick leaves were adjusted by the number of Ibermutua-affiliated persons in each period. Results: In March 2020, there was an unprecedented (116%) increase in total sick leaves, mainly due to infectious and respiratory diseases. Men and women were equally affected. All activity sectors were impacted, with the highest increase (457%) observed among health-related workers, especially due to contagious disease. The incidences of sick leaves were heterogeneous among different regions. Cost-analysis of sick leaves during the first trimester of 2020 compared with in previous years showed 40.3% increment (mean 2,813 vs. 2,005 € per 100 affiliated workers). Conclusions: The SARS-COV2 pandemic is having a huge impact on workers' health, as shown by data regarding sick leaves in March 2020. This is associated with greater economic burden for companies, both due to the cost associated with sick leaves and the losses in productivity due to confinement.

Skin and Arterial Wall Deposits of 18F-NaF and Severity of Disease in Patients with Pseudoxanthoma Elasticum.

Pseudoxanthoma elasticum (PXE) is a genetic disease characterized by the calcification of elastin fibers. Our aim was to quantify vascular calcification in the arteries and the deposition of 18F-sodium-fluoride (18F-NaF) in the skin and vessel walls with positron emission tomography/computed tomography. This was an observational study including 18 patients with PXE. Vascular calcification was measured in Agatston units, and deposition in the skin and vessel walls was shown using target-to-background ratio (TBR). Severity of the disease was scored by Phenodex. We found higher vascular calcification in the popliteal, femoral, and aortic arch vessels compared to other vascular regions; however, the uptake of radiotracer was the highest in the aorta and femoral arteries. In the skin, the highest uptake was observed in the neck and the axillae. There was no significant association between 18F-NaF deposition in the arteries or skin and the global Phenodex score. In contrast, the Phenodex score was significantly associated in univariate analyses with the averaged vascular calcium score (p < 0.01). In the neck, patients with higher skin Phenodex scores exhibited higher radiotracer uptake. As a conclusion, because vascular calcification is physiological, our data suggested that the detection of cutaneous (neck) 18F-NaF deposits might serve to monitor the calcification process in the short-term for patients with PXE.

Subclinical Arteriosclerosis is Associated With Common Vascular Risk Factors in Long-Term Survivors of Testicular Cancer.

Cardiovascular disease risk is increased in survivors of testicular cancer because of exposure to treatment (chemotherapy and radiotherapy), as well as modification in lifestyle. Our aim was to assess the presence of subclinical arteriosclerosis in survivors of testicular cancer in comparison with a control group. This was a cross-sectional, observational, case-control study including 50 survivors of Germ Cell Tumor (GCT) (14 years of follow-up) and 53 age-matched controls with no cancer. We registered clinical data, cardiovascular risk factors, physical and Mediterranean questionnaires, intima-media thickness and plaque at carotid and femoral arteries by ultrasound, calcium score at the abdominal aorta, and liver steatosis by computed tomography, and applied analytical tests to quantify metabolic risk factors and inflammation markers. Patients showed a trend toward greater intima-media thickness (IMT) and plaques than controls, as well as a higher calcium score in the abdominal aorta. Remarkably, patients had higher waist circumference, insulin resistance (HOMA-IR), and liver steatosis, but lower physical activity and high-density lipoprotein (HDL) cholesterol than controls (all p < 0.05). In multivariate analyses, only common vascular risk factors were associated with subclinical arteriosclerosis. As a conclusion, in our study, a higher rate of subclinical arteriosclerosis in testicular cancer survivors was associated with classical metabolic risk factors and lifestyle, but not with exposure to chemotherapy.

Genetic variants in the LPL and GPIHBP1 genes, in patients with severe hypertriglyceridaemia, detected with high resolution melting analysis.

INTRODUCTION: Pathogenic variants in lipoprotein lipase (LPL) and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) have been described in patients with severe hypertriglyceridaemia. We aimed to optimise high resolution melting (HRM) assays to detect the presence of functional variants in these genes. METHODS: One hundred and sixteen patients with severe hypertriglyceridaemia were studied. HRM assays were optimised to scan exons and splice junctions in LPL and GPIHBP1. Sanger sequencing was the reference method. Next-generation-sequencing (NGS) was performed in five patients, including one with Familial Chylomicronemia syndrome (FCS). RESULTS: We identified 15 different variants in LPL and 6 in GPIHBP1. The variants revealed with NGS were also detected with HRM, including a rare premature stop codon in LPL (p.Trp421*) and two LPL pathogenic variants in the patient with FCS (p.His80Arg + p.Gly215Glu). Having multiple functional variant alleles was associated with pancreatitis onset at younger ages and higher baseline triglycerides. CONCLUSIONS: Our HRM assays detected the presence of functional gene variants that were confirmed with Sanger and NGS sequencing. The presence of multiple functional variant alleles was associated with differences in the clinical profile. Therefore, these assays represent a reliable, cost-effective tool that can be used to complement the NGS approach for gene scanning.

Omega 3 fatty acids induce a marked reduction of apolipoprotein B48 when added to fluvastatin in patients with type 2 diabetes and mixed hyperlipidemia: a preliminary report.

BACKGROUND: Mixed hyperlipidemia is common in patients with diabetes. Statins, the choice drugs, are effective at reducing lipoproteins that contain apolipoprotein B100, but they fail to exert good control over intestinal lipoproteins, which have an atherogenic potential. We describe the effect of prescription omega 3 fatty acids on the intestinal lipoproteins in patients with type 2 diabetes who were already receiving fluvastatin 80 mg per day. METHODS: Patients with type 2 diabetes and mixed hyperlipidemia were recruited. Fasting lipid profile was taken when patients were treated with diet, diet plus 80 mg of fluvastatin and diet plus fluvastatin 80 mg and 4 g of prescription omega 3 fatty acids. The intestinal lipoproteins were quantified by the fasting concentration of apolipoprotein B48 using a commercial ELISA. RESULTS: The addition of 4 g of prescription omega 3 was followed by significant reductions in the levels of triglycerides, VLDL triglycerides and the triglyceride/HDL cholesterol ratio, and an increase in HDL cholesterol (P < 0.05). Fluvastatin induced a reduction of 26% in B100 (P < 0.05) and 14% in B48 (NS). However, the addition of omega 3 fatty acids enhanced this reduction to 32% in B100 (NS) and up to 36% in B48 (P < 0.05). CONCLUSION: Our preliminary findings therefore suggest an additional benefit on postprandial atherogenic particles when omega 3 fatty acids are added to standard treatment with fluvastatin.

[Usefulness of the ankle-arm index for detection of peripheral arterial disease in a working population of Junta de Andalucía at Málaga]. / Rentabilidad del índice tobillo-brazo para la detección de enfermedad arterial periférica en población laboral de la Junta de Andalucía en Málaga.

BACKGROUND AND OBJECTIVE: Detection of asymptomatic peripheral arterial disease increases the risk of vascular morbibity and mortality. We aimed to estimate the prevalence of clinical and subclinical peripheral arterial disease using the ankle-arm index (AAI) as diagnostic tool in a working population. SUBJECTS AND METHOD: We included 450 workers, older than 50 years old, attending voluntary regular health check-up at Centro de Prevención de Riesgos Laborales de la Junta de Andalucía in Málaga (Spain). We recorded clinical and anthopometrical data. Blood samples were taken after an overnight fast. Vascular risk was calculated using Framinghan and SCORE scales. Every participant was asked for symptoms of intermittent claudicatio and AAI was measured. AAI was considered normal within 0.9-1.3 values. RESULTS: Most of our workers were at low- or moderate vascular risk. Only 48 (10.6%) of individuals had an abnormal AAI: 9 (2%) showed an AAI<0.9 and 39 (8.6%) showed an AAI>1.3. An AAI<0.9 was found in 19% of those with a SCORE risk > or = 5%, and in 11% of those having a Framinghan risk > or = 20%. Intermittent claudication was present in 4 out of 9 (44%) of those having an AAI<0.9 and in 7 out of 402 (1.7%) with a normal AAI. CONCLUSIONS: Systematic screening of peripheral arterial disease using the AAI is not recommended in active working population over 50 years-old of age. Thus, AAI measurement is indicated only for those individuals suffering from intermitent claudicatio and those who are at moderate- or high vascular risk.