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Aim: The aim was to study the effect of two low-calorie, high-protein (HP) diets, with most of the protein coming from animal or plant sources, on glycaemic and other cardiometabolic outcomes in subjects with overweight or obesity and glucose metabolism disorders., Materials and Methods: A total of 117 participants aged >18 years with body mass index over 27.5 kg/m 2 and prediabetes or type 2 diabetes mellitus (T2DM) were randomized to one of two HP low-calorie diets (35% of total calories from protein), in which 75% of the protein was from either plant-based sources (HPP) or animal sources (HPA). For both diets, 30% and 35% of the total calories were from fat and carbohydrates, respectively. The dietary intervention lasted 6 months., Results: Both diets improved body composition to a similar extent, including weight loss (-8.05 ± 5.12 kg for the HPA diet and -7.70 ± 5.47 kg for the HPP diet at 6 months) and fat mass, mainly visceral fat. Both diets had a similar beneficial effect on glucose metabolism, including fasting glucose, insulin, homeostasis model assessment of insulin resistance index and glycated haemoglobin. Other biochemical parameters, including lipid profiles, liver enzymes, adipokines and inflammatory biomarkers, similarly improved in both groups. Fasting incretins, mainly glucagon-like peptide 1, decreased significantly in both groups, and this effect correlated with weight loss., Conclusions: Low-calorie HP diets improved body composition, glucose metabolism and other cardiometabolic outcomes, regardless of protein source (either animal or plant sources), in outpatients with prediabetes or T2DM., Clinical Trial Registration: The clinical trial was registered in ClinicalTrials.gov (identifier: NCT05456347) https://clinicaltrials.gov/study/NCT05456347?term=NCT05456347&rank=1., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Delirium or an acute confusional state (ACS) is characterised as being a frequent and complex hospital complication in older adult patients, which can affect their level of independence and increase patient morbidity and mortality. Critically ill patients in the intensive care unit (ICU) frequently develop ICU delirium, leading to longer hospital and ICU stays, increased mortality and long-term impairment., Objectives: This review aims to assess existing evidence of interventions that can be considered effective for the management and prevention of delirium in ICUs, reducing short-term morbidity and mortality, ICU and hospital admission times and the occurrence of other long-term complications., Methodology: For this systematic review, we searched Medline, PubMed, Cochrane Library, CINHAL, LILACS, SciELO and Dialnet from January 2018 to August 2024, in English, Spanish and French. MeSH descriptors were adjusted to search the different databases. We also checked Prospero for ongoing systematic reviews., Main Results: The electronic search yielded a total of 2656 studies, of which 14 trials met the eligibility criteria, with a total of 14,711 participants. We included eight randomised clinical trial (RCTs), four cohort analyses, one systematic review and one observational trial, including participants over 65 years admitted to the ICU. Ten of these studies were based on pharmacological interventions, three of them examined non-pharmacological interventions and the remaining study examined mixed (pharmacological and non-pharmacological) interventions. Six placebo RCTs were included, plus four reported comparisons between different drugs. Regarding non-pharmacological interventions, nursing programmes focused on optimising modifiable risk factors or the use of therapies such as bright light are emerging. Regarding mixed interventions, we found the combination of invasive techniques and with sedoanalgesia., Conclusions: Due to its satisfactory level of sedation, dexmedetomidine is presented as a viable option because, although olanzapine offers safer results, postoperative administration angiotensin inhibitor systems significantly reduced the incidence of delirium. As for propofol, no significant differences were found. Among the non-pharmacological and mixed therapies, bright light therapy was able to reduce the incidence of delirium, and the combination of epidural/general anaesthesia was effective in all subtypes of delirium. Concerning the remaining interventions, the scientific evidence is still insufficient to provide a definitive recommendation.

Background: The Mediterranean Diet (MedDiet) is the dietary pattern par excellence for managing and preventing metabolic diseases, such as Type 2 Diabetes (T2DM). The MedDiet incorporates spices and aromatic herbs, which are abundant sources of bioactive compounds. The aim of this study was to analyze the effect of all aromatic herbs and spices included in the MedDiet, such as black cumin, clove, parsley, saffron, thyme, ginger, black pepper, rosemary, turmeric, basil, oregano, and cinnamon, on the glycemic profile in T2DM subjects., Methods: PubMed, Web of Science, and Scopus databases were searched for interventional studies investigating the effect of these aromatic herbs and spices on the glycemic profile in T2DM subjects., Results: This systematic review retrieved 6958 studies, of which 77 were included in the qualitative synthesis and 45 were included in the meta-analysis. Our results showed that cinnamon, turmeric, ginger, black cumin, and saffron significantly improved the fasting glucose levels in T2DM subjects. The most significant decreases in fasting glucose were achieved after supplementation with black cumin, followed by cinnamon and ginger, which achieved a decrease of between 27 and 17 mg/dL., Conclusions: Only ginger and black cumin reported a significant improvement in glycated hemoglobin, and only cinnamon and ginger showed a significant decrease in insulin.

Background: APOE gene encoded a multifunctional protein in lipid metabolism, also associated with inflammatory markers. Type 2 diabetes (T2D) is a complex metabolic disease related to increased blood glucose, triglycerides and VLDL and associated with different dyslipidaemias. The aim of this study was to analyze whether the APOE genotype could determining the risk of developing T2D in a large cohort of workers., Material and Methods: Data from the Aragon Workers Health Study (AWHS) (n=4895) were used to investigate the relationship between glycemic levels and APOE genotype. All patients in the AWHS cohort had their blood drawn after an overnight fast and laboratory tests were performed on the same day as the blood drawn. Dietary and physical assessment was assessed by face-to-face interview. APOE genotype was determined by the Sanger sequencing method., Results: The relationship between APOE genotype and glycemic profile showed that glucose, Hb1Ac, insulin and HOMA levels did not seem to be associated with the APOE genotype (p=0.563, p=0.605, p=0.333 and p=0.276, respectively). In addition, the T2D prevalence did not show an association with the APOE genotype (p=0.354). Along the same lines, blood glucose levels and T2D prevalence did not show association with the APOE allele. Shift work had some effect on the glycaemic profile, showing that night shift workers have significantly lower levels of glucose, insulin and HOMA (p<0.001). However, the APOE genotype did not show difference in the concentration of glycaemic parameters adjusting by sex, age and BMI, work shift and dietary parameters., Conclusion: Glycemic profile and T2D prevalence did not show any significant association with the APOE genotype. Besides, individuals, who worked in non-rotating night shift showed significantly lower glycemic levels, while workers in the morning-afternoon-night shift showed significantly higher values., (Copyright © 2023 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Previous research has indicated that the COVID-19 outbreak had a negative impact on the diagnosis and management of cardiometabolic diseases. Our aim was to analyze the impact of the COVID-19 pandemic on the management of dyslipidemia and type 2 diabetes (T2D) in the Aragon region of Spain., Methods: We conducted an observational retrospective study, which included data from all patients diagnosed with active T2D or dyslipidemia in Aragon during 2019-2021. Data was collected from the BIGAN platform, a big database that includes all healthcare data from the Aragon population. Clinical, biochemical, and pharmacological prescription information was obtained for each patient and for each year., Results: Out of the total population of 1,330,000 in the Aragon region, 90,000 subjects were diagnosed with T2D each year, resulting in a prevalence of approximately 7%. The COVID-19 pandemic resulted in a decrease in the prevalence of this disease and a lower incidence during the year 2020. In addition, patients with T2D experienced a deterioration of their glucose profile, which led to an increase in the number of patients requiring pharmacological therapy. The prevalence of dyslipidemia was approximately 23.5% in both 2019 and 2020 and increased to 24.5% in 2021. Despite the worsening of the anthropometric profile, the lipid profile improved significantly throughout 2020 and 2021 compared to 2019. Moreover, the number of active pharmacological prescriptions increased significantly in 2021., Discussion: Our findings suggest that the overload of the health system caused by the COVID-19 pandemic has resulted in an underdiagnosis of T2D. Moreover, patients with T2D experienced a worsening of their glycemic profile, an increase in their pharmacological requirements, and lower performance of their analytical determinations. Dyslipidemic subjects improved their lipid profile although the value of lipid profile determination decreased between 2020 and 2021., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mateo-Gallego, Gracia-Rubio, Garza, Cebollada, Pérez-Calahorra, Bayona-Sánchez, Bujeda-Hernández, Jarauta, Sánchez-Calavera and Lamiquiz-Moneo.)

Background: We investigated the postprandial effects of an alcohol-free beer with modified carbohydrate (CH) composition compared to regular alcohol-free beer., Methods: Two randomized crossover studies were conducted. In the first study, 10 healthy volunteers received 25 g of CH in four different periods, coming from regular alcohol-free beer (RB), alcohol-free beer enriched with isomaltulose and a resistant maltodextrin (IMB), alcohol-free beer enriched with resistant maltodextrin (MB), and a glucose-based beverage. In the second study, 20 healthy volunteers were provided with 50 g of CH from white bread (WB) plus water, or with 14.3 g of CH coming from RB, IMB, MB, and extra WB. Blood was sampled after ingestion every 15 min for 2 h. Glucose, insulin, incretin hormones, TG, and NEFAs were determined in all samples., Results: The increase in glucose, insulin, and incretin hormones after the consumption of IMB and MB was significantly lower than after RB. The consumption of WB with IMB and MB showed significantly less increase in glucose levels than WB with water or WB with RB., Conclusions: The consumption of an alcohol-free beer with modified CH composition led to a better postprandial response compared to a conventional alcohol-free beer.

Introduction and Objectives: The lower prevalence of type 2 diabetes mellitus (T2DM) in patients with heterozygous familial hypercholesterolemia (HeFH) could explain why T2DM has not always been identified as an independent predictor of cardiovascular disease (CVD) in different familial hypercholesterolemia cohort studies. The aim of the present study was to evaluate clinical and genetic aspects of HeFH patients with T2DM in the dyslipidemia registry of the Spanish Arteriosclerosis Society., Methods: HeFH patients were classified according to the presence or absence of T2DM. The clinical, biochemical and genetic characteristics of the 2 groups were compared., Results: Of the 2301 patients with primary hypercholesterolemia included in the registry, 1724 with a probable or definite diagnosis according to the Dutch Lipid Clinic Network score were finally included. HeFH patients with T2DM had a higher rate of CVD and a less favorable lipid profile, with higher total cholesterol (366.9±86.7mg/dL vs 342.0±74.7mg/dL; mean difference 24.894; 95%CI, 5.840-43.949) and non-high-density lipoprotein cholesterol (316.9±87.8mg/dL vs 286.4±75.4mg/dL; mean difference 30.500; 95%CI, 11.211-49.790) levels. No significant differences were found between the groups concerning the specific type of HeFH-causing mutation (P=.720). After adjustment for major risk factors, logistic regression analysis confirmed a relationship between T2DM and the presence of CVD (OR, 2.01; 95%CI, 1.18-3.43; P=.010)., Conclusions: HeFH patients with T2DM have a higher rate of CVD and a less favorable lipid profile, regardless of genetic mutation type. In these patients, T2DM is associated with the presence of CVD., (Copyright © 2019 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background & Aims: It has not been elucidated if an energy-restricted diet with high protein content could induce a benefit in insulin resistance in subjects with type 2 diabetes (T2DM); and if an adipose tissue functionality improvement could mediate this effect. We aimed to assess the effect of energy-restricted diets with standard (18% from total calories; SP) vs high (35%) protein (HP), mainly coming from lean animal source, composition on glucose metabolism and adipokine concentration in overweight and obese subjects with T2DM. HOMA-IR change was the primary outcome., Methods: Six-month weight-loss intervention including 73 subjects (43.8% men, 55.6 ± 8.37 aged and 32.8 ± 3.67 of BMI) with T2DM that were randomized to follow one of two calorie-restricted diets with the following distribution of calories: 18% (0.75 [95%CI: 0.71-0.78] g/kg/day) protein, 52% carbohydrates and 30% fat, or 35% (1.34 [95%CI: 1.27-1.41] g/kg/day) protein, 35% carbohydrates, and 30% fat. Anthropometric, clinical, biochemical (involving leptin, RBP4 and adiponectin) and lifestyle assessments were performed., Results: Sixty-seven participants completed the study. Weight loss homogenously decreased among diets. HOMA-IR in HP diminished 2-fold than in SP diet (P = 0.023 and P = 0.004 at 3 and 6-months between diets). Participants following HP diet showed higher decrease in insulin, in glucose at 6-months (P = 0.004) and in HbA1c at 3-months (P = 0.003). RBP4 and leptin significantly decreased in both diets although no differences were found between diets. Adiponectin increased by 6.05% and 29.9% at 3-months in SP and HP diets, respectively (P = 0.167), and 23.7% and 53.5% at 6-months in SP and HP diets (P = 0.219). Adiponectin variation was inversely correlated with HbA1c, insulin and HOMA-IR changes at 6-months., Conclusions: An energy-restricted diet containing 35% of total calories coming from protein lead to a greater improvement in glucose homeostasis, indicated by HOMA-IR and fasting plasma insulin concentrations, irrespective of weight loss in subjects with prediabetes or early stages of T2DM. This effect cannot be explained by changes in plasma concentration of adipokines., Clinical Trial Registration: The clinical trial has been registered in ClinicalTrials.gov (Identifier: NCT02559479)., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: The quality of carbohydrates has an essential role in nutritional management of type 2 diabetes mellitus (T2DM) because of its substantial impact on glucose homeostasis. Alcohol-free beer has beneficial bioactive components but it has a relatively high glycemic-index so its consumption is restricted in diabetic subjects. We aimed to explore the effect of an alcohol-free beer with modified carbohydrate composition almost completely eliminating maltose and adding isomaltulose (16.5 g/day) and a resistant maltodextrin (5.28 g/day) in comparison to a regular alcohol-free beer on glycemic control of diabetic subjects with overweight or obesity., Design: We randomized 41 subjects into two groups: a) consumption of 66 cL/day of; regular alcohol-free beer for the first 10 weeks and 66 cL/day of alcohol-free beer with modified carbohydrate composition for the next 10 weeks; b) the same described intervention in opposite order. There was a washout period for 6-8 weeks between the two interventions. Participants were counseled to adhere to a healthy diet for cardiovascular health and to increase physical activity. Clinical, biochemical, anthropometric, lifestyle and satiety assessments were performed at the beginning and at the end of each period., Results: Subjects showed significantly weight loss after the two ten weeks periods (-1.69 ± 3.21% and -1.77 ± 3.70% after experimental and regular alcohol-free beers, respectively, P = 0.881). Glucose and glycated hemoglobin did not significantly change after any period. Insulin concentrations and HOMA-IR significantly decreased (-11.1 [-21.3-4.64]% and -1.92 ± 32.8% respectively) after the intake of experimental alcohol-free beer but not after regular alcohol-free beer. Reductions remained statistically significant after adjusting for weight loss, energy intake, physical activity and intervention order. Subjects reported higher satiety scores after consuming experimental alcohol-free beer., Conclusions: An alcohol-free beer including the substitution of regular carbohydrates for low doses of isomaltulose and the addition of a resistant maltodextrin within meals led to an improvement in insulin resistance in subjects with T2DM and overweight or obesity., Clinical Trial Registration: The clinical trial has been registered in ClinicalTrials.gov (Identifier: NCT03337828)., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Dyslipidemia is a well-established modifiable cardiovascular risk. Although statins can reduce LDLc by 50-60%, less than 20% of patients with high risk of CVD achieve LDL targets. The aim of this systematic review is to evaluate the effect of the nutraceutical, bergamot ( Citrus bergamia ), on lipid parameters in humans. PubMed, Embase, Cochrane Library, and Google Scholar databases were searched for interventional and observational studies investigating the effect of bergamot on lipid profile in humans. This systematic review retrieved a total of 442 studies of which 12 articles fulfilled the eligibility criteria and were included in the qualitative synthesis. Based on data, 75% of studies showed a significant decrease in total cholesterol, triglycerides and LDLc. The decrease in total cholesterol varied from 12.3% to 31.3%, from 7.6% to 40.8% in LDLc and from 11.5% to 39.5% in triglycerides. Eight trials reported HDLc increase after intervention with bergamot. Overall, a dose-dependent and possible synergistic effect when administering with statins can be deducted from these trials. It is essential to point out that studies had heterogeneous designs and scientific quality of studies was quite limited. Promising findings reveal an alternative therapeutic option in dyslipidemia management with bergamot supplementation, especially in subjects with statins intolerance.

The aim of our study was to investigate a large cohort of overweight subjects consuming a homogeneous diet to identify the genetic factors associated with weight loss that could be used as predictive markers in weight loss interventions. We retrospectively recruited subjects (N = 788) aged over 18 years with a Body Mass Index (BMI) between 25 and 40 kg/m 2 who were treated at our lipid unit for at least one year from 2008 to 2016, and we also recruited a control group (168 patients) with normal BMIs. All participants received counselling from a nutritionist that included healthy diet and physical activity recommendations. We genotyped 25 single nucleotide variants (SNVs) in 25 genes that were previously associated with obesity and calculated genetic scores that were derived from 25 SNVs. The risk allele in CADM2 showed a higher frequency in overweight and obese subjects than in controls (p = 0.007). The mean follow-up duration was 5.58 ± 2.68 years. Subjects with lower genetic scores showed greater weight loss during the follow-up period. The genetic score was the variable that best explained the variations in weight from the baseline. The genetic score explained 2.4% of weight change variance at one year and 1.6% of weight change variance at the end of the follow-up period after adjusting for baseline weight, sex, age and years of follow-up.

A 60-year-old male with familial combined hyperlipidemia, ischemic heart disease and type 2 diabetes. Since childhood, intolerance to intense exercise. The patient was diagnosed of McArdle's disease after an episode of rhabdomyolysis associated with statins as treatment after a myocardial infarction. Since then, he had been treated with diet, fibrates and ezetimibe with good tolerance, despite this, LDL cholesterol (cLDL) remained >180mg/dl. He started to be treated with alirocumab 150mg/sc every 14 days, with excellent clinical response and a decrease in cLDL to 15mg/dl. Our case shows that PCSK9 inhibitors are effective and safe in patients with muscle diseases who have statin contraindication, and they are a good therapeutic tool for these patients., (Copyright © 2018 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Aims: The aim of this work was to compared the effect of lipid lowering drugs among familial hypercholesterolemia (FH) subjects with a functional mutation in LDLR (LDLR FH) and FH with the p.(Leu167del) mutation in APOE., Methods: We retrospectively selected all adults with the p.(Leu167del) mutation on lipid-lowering treatment (n = 22) attending the Lipid Unit at the Hospital Miguel Servet. Age and sex matched LDLR FH from the same Unit were randomly selected as a control group (n = 44)., Results: The mean percentage reduction in LDLc was significantly higher in the p.(Leu167del) carriers (-52.1%) than in the LDLR FH (-39.7%) (p = 0.040) when on high intensity statins. Similar differences between groups were observed in non-HDLc -49.4% and -36.4%, respectively (p = 0.030)., Conclusions: Subjects with p.(Leu167del) mutation have a higher lipid-lowering response to statins with or without ezetimibe than LDLR FH. This supports the use of genetics for a more efficient management of FH., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Familial chylomicronemia syndrome (FCS) is an extremely rare lipoprotein disorder caused by mutations in at least 5 genes of the lipoprotein lipase (LPL) complex., Objective: This work shows the molecular analysis of patients diagnosed with FCS, who attended the Spanish Arteriosclerosis Society lipid units and were included in the National Dyslipidemia Registry., Methods: Among the 238 patients registered with severe hypertriglyceridemia (fasting triglycerides >1000 mg/dL), 26 were diagnosed with FCS as they had confirmed postheparin plasma LPL activity deficiency and/or homozygosity for loss-of-function mutations in LPL, GPIHBP1, APOC2, LMF1, or Apolipoprotein A5 (APOA5)., Results: Among the 26 FCS cases, 23 had mutations in the homozygous state: 19 in LPL and 4 in the GPIHBP1 gene. The molecular analysis revealed 3 novel mutations: 2 in LPL, in 2 unrelated patients (c.312delA; p.Asp105Thrfs*66 and c.629A>G; p.His210Arg), and 1 in GPHIBP1 in a third patient (c.502delC; p.Leu168Serfs*83). These 3 patients had confirmed lack of LPL activity. Three additional patients with confirmed LPL activity deficiency were heterozygous carriers of mutations in the genes analyzed. Among these, we found 2 novel mutations in APOA5 (c.50-1G>A and c.326&#95;327insC; p.Tyr110Leufs*158)., Conclusion: We have identified 5 novel pathogenic mutations: 2 in LPL, 1 in GPIHBP1, and 2 in the APOA5 gene. The genetic defaults accounting for the LPL activity deficiency of 23 of them have been clearly identified and 3 patients, who harbored mutations in heterozygosity, were diagnosed based on LPL activity deficiency, which raises the question of the involvement of new genes in the manifestation of FCS., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: High ferritin concentration is associated with hypertriglyceridemia, although it is not elucidated if iron overload has a causal role., Objective: To evaluate the efficacy of repeated phlebotomies in patients with iron overload and hypertriglyceridemia., Methods: Twelve weeks, 1:1 randomized, parallel-groups trial conducted at a University Hospital Lipid Clinic, including 86 subjects aged 18-70 years with serum ferritin >300 ng/mL in men or >200 ng/mL in women and triglycerides >200 mg/dL. Participants underwent: (1) three phlebotomies (every 3 weeks) and lipid-lowering dietary counseling or (2) lipid-lowering dietary counseling. The main outcome measured was the mean difference in percent change in triglyceride concentration between groups after the intervention. The mean differences in percent change of other clinical and biochemical variables (including cytokines and proinflammatory markers) after the intervention were also evaluated., Results: Subjects who received phlebotomies showed a significant improvement in iron metabolism. The mean percent change in triglycerides between groups was -4.68 [-20.8, 11.4]%, P = .721. Retinol-binding protein 4 decreased by 9.98 ± 21.7% after phlebotomies, with a mean percent change between groups of -14.2 [-25.8, -2.73]%, P = .017, and correlated to gamma glutamyl transferase, alanine aminotransferase and aspartate aminotransferase change. Subjects with a large reduction in hepcidin showed a large improvement in liver enzymes and proinflammatory markers., Conclusions: A lipid-lowering diet plus a substantial reduction in iron deposits with repeated phlebotomies in subjects with hyperferritinemia and hypertriglyceridemia did not reduce triglyceride concentration in comparison with a lipid-lowering diet. Iron depletion for lipid management in these patients is not supported., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: Approximately 20% to 40% of clinically defined familial hypercholesterolemia cases do not show a causative mutation in candidate genes, and some of them may have a polygenic origin. A cholesterol gene risk score for the diagnosis of polygenic hypercholesterolemia has been demonstrated to be valuable to differentiate polygenic and monogenic hypercholesterolemia. The aim of this study was to determine the contribution to low-density lipoprotein cholesterol (LDL-C) of the single nucleotide variants associated with polygenic hypercholesterolemia in probands with genetic hypercholesterolemia without mutations in candidate genes (nonfamilial hypercholesterolemia genetic hypercholesterolemia) and the genetic score in cascade screening in their family members., Methods: We recruited 49 nonfamilial hypercholesterolemia genetic hypercholesterolemia families (294 participants) and calculated cholesterol gene scores, derived from single nucleotide variants in SORT1, APOB, ABCG8, APOE and LDLR and lipoprotein(a) plasma concentration., Results: Risk alleles in SORT1, ABCG8, APOE, and LDLR showed a statistically significantly higher frequency in blood relatives than in the 1000 Genomes Project. However, there were no differences between affected and nonaffected members. The contribution of the cholesterol gene score to LDL-C was significantly higher in affected than in nonaffected participants (P = .048). The percentage of the LDL-C variation explained by the score was 3.1%, and this percentage increased to 6.9% in those families with the highest genetic score in the proband., Conclusions: Nonfamilial hypercholesterolemia genetic hypercholesterolemia families concentrate risk alleles for high LDL-C. Their contribution varies greatly among families, indicating the complexity and heterogeneity of these forms of hypercholesterolemias. The gene score explains a small percentage of LDL-C, which limits its use in diagnosis., (Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Clinical registries are a very effective tool to verify the usual clinical practice, to compare clinical strategies and to improve the knowledge of diagnostic and therapeutic new procedures., Methods: The National Registry of Dyslipemias of the Spanish Society of Arteriosclerosis (SEA) is an on-line, retrospective and prospective database where the different Spanish lipid units accredited by the SEA introduce data from patients with disorders of lipid metabolism., Results: The registry was created in 2013, and since then clinical, analytical, genetic and evolutionary data of 4,449 patients have been introduced until June 2017. In the last year the registry has given rise to a considerable number of international publications and there are several more in progress. An ambitious incentive plan for inclusion of patients has been initiated to get the SEA registry as a global reference that helps to improve the knowledge and clinical management of these patients., Conclusions: From the coordinating group of the registry we encourage all SEA partners to collaborate in the multiple forms that the registry allows, and to make it an international scientific reference., (Copyright © 2017. Publicado por Elsevier España, S.L.U.)

Context: Approximately 20% to 40% of clinically defined familial hypercholesterolemia (FH) cases do not show a causative mutation in candidate genes (mutation-negative FH), and some of them may have a polygenic origin., Objective: The aim of this work was to study the prevalence of ABCG5/G8 genetic variants in mutation-negative FH, as defects in these genes relate to intestinal hyperabsorption of cholesterol and thus ABCG5/G8 variants could explain in part the mechanism of hypercholesterolemia., Design, Setting, and Patients: We sequenced the ABCG5/G8 genes in 214 mutation-negative FH and 97 controls. Surrogate markers of cholesterol absorption (5α-cholestanol, β-sitosterol, campesterol, stigmasterol, and sitostanol) were quantified by high-performance liquid chromatography-tandem mass spectrometry in both studied groups., Results: We found 8 mutation-negative FH patients (3.73%) with a pathogenic mutation in ABCG5/G8 genes. We observed significantly higher concentration of surrogate markers of cholesterol absorption in mutation-negative FH than in controls. In addition, we found significantly higher concentrations of cholesterol absorption markers in mutation-negative FH with ABCG5/G8 defects than in mutation-negative, ABCG5/G8-negative FH. A gene score reflecting the number of common single nucleotide variants associated with hypercholesterolemia was significantly higher in cases than in controls (P = .032). Subjects with a gene score above the mean had significantly higher 5α-cholestanol and stigmasterol than those with a lower gene score., Conclusions: Mutation-negative FH subjects accumulate an excess of rare and common gene variations in ABCG5/G8 genes. This variation is associated with increased intestinal absorption of cholesterol, as determined by surrogate makers, suggesting that these loci contribute to hypercholesterolemia by enhancing intestinal cholesterol absorption., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vulnerable to type 2 diabetes mellitus (T2DM), although the mechanism is unknown. The aims of the present study were to assess the effects of low density lipoprotein (LDL) cholesterol concentration and the presence of FH-causing mutations on T2DM prevalence in HeFH. Data were collected from the Dyslipidemia Registry of the Spanish Arteriosclerosis Society. Inclusion criteria were definite or probable HeFH in patients aged ≥18 years. T2DM prevalence in HeFH patients was compared with data of the general population. 1732 patients were included. The prevalence of T2DM was lower in patients with HeFH compared with the general population (5.94% vs 9.44%; OR: 0.606, 95% CI 0.486-0.755, p < 0.001). Risk factors for developing T2DM were male sex, age, body mass index, hypertension, baseline triglyceride levels and years on statin therapy. The prevalence of T2DM in HeFH patients was 40% lower than that observed in the general population. Gene mutations and LDL cholesterol concentrations were not risk factors associated with the prevalence of T2DM in patients with HeFH. The prevalence of T2DM in patients with HeFH was 40% lower than in the general population matched for age and sex.

Background and Aims: Familial hypercholesterolemia (FH) is a high cardiovascular risk condition. Less than 20% of patients achieve the LDL targets. Although PCSK9 inhibitors improve control and reduce cardiovascular events, official recommendations for their use are restrictive. We aim to assess the number of FH patients suitable for PCSK9 inhibition according to the European guidelines., Methods: A total of 2685 FH patients, with a minimum follow-up of 6 months, included in the Dyslipidemia Registry of the Spanish Arteriosclerosis Society, were sorted according to the intensity of their lipid-lowering therapy (LLT) and LDL cholesterol levels achieved. The number of patients who met the recommendations for PCSK9 inhibition treatment according to the European Atherosclerosis Society (ESC/EAS), Spanish Arteriosclerosis Society and the European Medicines Agency was calculated., Results: In total, 1573 patients were on high-intensity LLT; 607 were on moderate-intensity statins; 82 were on low-intensity LLT, and 423 were neither on statins nor on ezetimibe in the last visit registered. The mean LDL reduction among those on high-intensity LLT was 54%. Ninety-one percent of patients on high-intensity LLT had an LDL below 5.2 mmol/L, 53% below 3.4 mmol/L, and 23% below 2.6 mmol/L. Only 12% of FH patients with cardiovascular disease achieved 1.8 mmol/L. Despite this, only 17% of patients qualified for PCSK9 inhibition according to ESC/EAS guidelines., Conclusions: For patients with a condition that exposes them to high cardiovascular risk and who have extreme difficulties in achieving LDL targets, wider access to PCSK9 inhibitor therapy is warranted., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction and Objectives: The equations used in the general population to calculate cardiovascular risk are not useful in genetic hypercholesterolemia (GH). Carotid plaque detection has proved useful in cardiovascular prediction and risk reclassification but there have been no studies of its usefulness in GH. The aim of this study was to determine the association between the presence of carotid artery plaque and the occurrence of cardiovascular events in patients with GH., Methods: This study included 1778 persons with GH. The mean follow-up until the occurrence of cardiovascular events was 6.26 years. At presentation, the presence of carotid artery plaque was studied by high-resolution ultrasound., Results: Carotid artery plaque was found in 661 (37.2%) patients: 31.9% with familial hypercholesterolemia, 39.8% with familial combined hyperlipidemia, 45.5% with dysbetalipoproteinemia, and 43.2% with polygenic hypercholesterolemia. During follow-up, 58 patients had a cardiovascular event. Event rates were 6354/100 000 (95%CI, 4432.4-8275.6) in the group with plaque and 1432/100 000 (95%CI, 730.6-2134.3) in the group without plaque, with significant differences between the 2 groups (P < .001). The relative risk of an event was 4.34 (95CI%, 2.44-7.71; P < .001) times higher in patients with plaque and was 2.40 (95%CI, 1.27-4.56; P = .007) times higher after adjustment for major risk factors. The number of carotid artery plaques was positively associated with the risk of cardiovascular events., Conclusions: Most cardiovascular events occur in a subgroup of patients who can be identified by carotid plaque detection. These results support the use of plaque screening in this population and should help in risk stratification and treatment in GH., (Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol with co-dominant transmission and high risk of cardiovascular disease (CVD), although with high variability among subjects. Currently, CVD stratification tools for heterozygous FH (HeFH) are not available. A definition of severe HeFH has been recently proposed by the International Atherosclerosis Society (IAS), but it has not been validated. Our study aims to see clinical characteristics and prevalence of CVD in subjects defined as severe HeFH by IAS criteria. Probable or definite HeFH introduced in the Dyslipidemia Registry of Spanish Arteriosclerosis Society were analyzed by the IAS criteria. Univariate and multivariate analysis was used to assess the association of CVD with the IAS criteria. About 1,732 HeFH cases were analyzed. Severe HeFH had higher prevalence of familial history of CVD, personal history of tendon xanthomas, LDL cholesterol, and CVD than nonsevere HeFH. A total of 656 (77.1%) and 441 (50.1%) of men and women, respectively, fulfilled the IAS criteria of severe HeFH. In the univariate analysis, subjects defined as severe HeFH showed odds ratio 3.016 (95% CI 3.136 to 4.257, p <0.001) for CVD. However, when traditional risk factors were included in the multivariate analysis, only the presence of cholesterol >400 mg/dl had a statistically significant association with CVD odds ratio 8.76 (95% CI 3.90 to 19.69, p <0.001). In conclusion, the IAS definition of severe HeFH is not significantly associated with CVD when adjusted for classic risk factors. Risk stratification in HeFH is an important issue, but the proposed criteria do not seem to solve this problem., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: A substantial proportion of individuals clinically diagnosed as familial hypercholesterolemia (FH) do not carry pathogenic mutations in candidate genes. Whether in them the high cholesterol trait is transmitted monogenically has not been studied., Objectives: We assessed the inheritance pattern, penetrance, and expression of high low-density lipoprotein (LDL)-cholesterol (LDLc) in families with genetic hypercholesterolemia (GH) without known causative mutations (non-FH-GH)., Methods: The study included probands with a clinical diagnosis of FH and their families attending 2 lipid clinics in Spain. Inclusion criteria for probands were LDLc >95th percentile, triglycerides <90th percentile, at least 1 first-degree family member with LDLc >90th percentile, >5 points in the Dutch Lipid Clinic Network criteria score, and absence of mutations in LDLR, APOB, PCSK9 or APOE. Eleven FH families with a LDLR mutation were also examined for comparison., Results: We analyzed 49 non-FH-GH probands and 277 first-and second-degree relatives. LDLc was >90th percentile in 37.8% of blood relatives, at concentrations similar to those of probands. LDLc had a normal distribution in non-FH-GH families, in contrast with a bimodal distribution in FH families. When a dominant model was tested, family-based association tests gave much lower heritability values for total cholesterol and LDLc in non-FH-GH (0.39 and 0.32, respectively) than in FH (0.78 and 0.61, respectively)., Conclusions: Non-FH-GH families have a milder lipid phenotype than genetically defined FH. The heritage pattern of LDLc in non-FH-GH does not fit with a monogenic disorder. Our findings support the concept that most non-FH-GHs are polygenic hypercholesterolemias., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Hypertriglyceridemia (HTG) is a common complex metabolic trait that results of the accumulation of relatively common genetic variants in combination with other modifier genes and environmental factors resulting in increased plasma triglyceride (TG) levels. The majority of severe primary hypertriglyceridemias is diagnosed in adulthood and their molecular bases have not been fully defined yet. The prevalence of HTG is highly variable among populations, possibly caused by differences in environmental factors and genetic background. However, the prevalence of very high TG and the frequency of rare mutations causing HTG in a whole non-selected population have not been previously studied., Methods: The total of 23,310 subjects over 18 years from a primary care-district in a middle-class area of Zaragoza (Spain) with TG >500 mg/dL were selected to establish HTG prevalence. Those affected of primary HTG were considered for further genetic analysis. The promoters, coding regions and exon-intron boundaries of LPL, LMF1, APOC2, APOA5, APOE and GPIHBP1 genes were sequenced. The frequency of rare variants identified was studied in 90 controls., Results: One hundred ninety-four subjects (1.04%) had HTG and 90 subjects (46.4%) met the inclusion criteria for primary HTG. In this subgroup, nine patients (12.3%) were carriers of 7 rare variants in LPL, LMF1, APOA5, GPIHBP1 or APOE genes. Three of these mutations are described for the first time in this work. The presence of a rare pathogenic mutation did not confer a differential phenotype or a higher family history of HTG., Conclusion: The prevalence of rare mutations in candidate genes in subjects with primary HTG is low. The low frequency of rare mutations, the absence of a more severe phenotype or the dominant transmission of the HTG would not suggest the use of genetic analysis in the clinical practice in this population.

Background and Aim: Different kinds of fatty acids can affect the synthesis, absorption, and elimination of cholesterol. This study was carried out to assess the associations of cholesterol metabolism with the intake of two meats with different fatty acid composition in healthy volunteers., Methods and Results: The study group was composed of 20 subjects (12 males and eight females; age, 34.4 ± 11.6 years; body mass index (BMI), 23.5 ± 2.3 kg/m(2); low-density lipoprotein (LDL) cholesterol, 2.97 ± 0.55 mmol/l; high-density lipoprotein (HDL) cholesterol, 1.61 ± 0.31 mmol/l; triglycerides (TG), 1.06 ± 0.41 mmol/l) who completed a 30-day randomized and cross-over study to compare the cholesterol metabolism effect of 250 g of low-fat lamb versus 250 g of high-fat lamb per day in their usual diet. Cholesterol absorption, synthesis, and elimination were estimated from the serum non-cholesterol sterol and oxysterol concentrations analyzed by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). No changes in weight, plasma lipids, or physical activity were observed across the study. Cholesterol intestinal absorption was decreased with both diets. Cholesterol synthesis and elimination decreased during the low-fat lamb dietary intervention (ρ = 0.048 and ρ = 0.005, respectively)., Conclusion: Acute changes in the diet fat content modify the synthesis, absorption, and biliary elimination of cholesterol. These changes were observed even in the absence of total and LDL cholesterol changes in plasma., Registration Number for Clinical Trials: ClinicalTrials.gov PRS, NCT02259153., (Copyright © 2015 Elsevier B.V. All rights reserved.)