Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS)

Familial chylomicronaemia syndrome (FCS) is a rare, inherited disorder characterised by impaired clearance of triglyceride (TG)-rich lipoproteins from plasma, leading to severe hypertriglyceridaemia (HTG) and a markedly increased risk of acute pancreatitis. It is due to the lack of lipoprotein lipase (LPL) function, resulting from recessive loss of function mutations in the genes coding LPL or its modulators. A large overlap in the phenotype between FCS and multifactorial chylomicronaemia syndrome (MCS) contributes to the inconsistency in how patients are diagnosed and managed worldwide, whereas the incidence of acute hypertriglyceridaemic pancreatitis is more frequent in FCS. A panel of European experts provided guidance on the diagn

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Reference values assessment in a Mediterranean population for small dense low-density lipoprotein concentration isolated by an optimized precipitation method

Bárbara Fernández-Cidón,1–3 Ariadna Padró-Miquel,1 Pedro Alía-Ramos,1 María José Castro-Castro,1 Marta Fanlo-Maresma,4 Dolors Dot-Bach,1 José Valero-Politi,1 Xavier Pintó-Sala,4 Beatriz Candás-Estébanez1 1Clinical Laboratory, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain; 2Department of Biochemistry, Molecular Biology and Biomedicine, Autonomous University of Barcelona (UAB), Barcelona, Spain; 3Department of Pharmacotherapy, Pharmacogenetics and Pharmaceutical Technology, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Spain; 4Cardiovascular Risk Unit, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain Background: High serum concentrations of small dense low-density lipoprotein cholesterol (sd-LDL-c) particles are associated with risk of cardiovascular disease (CVD). Their clinical application has been hindered as a consequence of the laborious current method used for their quantification. Objective: Optimize a simple and fast precipitation method to isolate sd-LDL particles and establish a reference interval in a Mediterranean population. Materials and methods: Forty-five serum samples were collected, and sd-LDL particles were isolated using a modified heparin-Mg2+ precipitation method. sd-LDL-c concentration was calculated by subtracting high-density lipoprotein cholesterol (HDL-c) from the total cholesterol measured in the supernatant. This method was compared with the reference method (ultracentrifugation). Reference values were estimated according to the Clinical and Laboratory Standards Institute and The International Federation of Clinical Chemistry and Laboratory Medicine recommendations. sd-LDL-c concentration was measured in serums from 79 subjects with no lipid metabolism abnormalities. Results: The Passing–Bablok regression equation is y = 1.52 (0.72 to 1.73) + 0.07x (−0.1 to 0.13), demonstrating no significant statistical differences between the modified precipitation method and the ultracentrifugation reference method. Similarly, no differences were detected when considering only sd-LDL-c from dyslipidemic patients, since the modifications added to the precipitation method facilitated the proper sedimentation of triglycerides and other lipoproteins. The reference interval for sd-LDL-c concentration estimated in a Mediterranean population was 0.04–0.47 mmol/L. Conclusion: An optimization of the heparin-Mg2+ precipitation method for sd-LDL particle isolation was performed, and reference intervals were established in a Spanish Mediterranean population. Measured values were equivalent to those obtained with the reference method, assuring its clinical application when tested in both normolipidemic and dyslipidemic subjects. Keywords: sd-LDL-c, small dense lipoprotein, sd-LDL reference value

Consensus on the statin of choice in patients with impaired glucose metabolism: results of the DIANA study

INTRODUCTION AND OBJECTIVES: Despite the recognized clinical benefit of statins on cardiovascular prevention, providing correct management of hypercholesterolaemia, possible adverse effects of their use cannot be disregarded. Previously published data shows that there is a risk of developing diabetes mellitus or experiencing changes in glucose metabolism in statin-treated patients. The possible determining factors are the drug characteristics (potency, dose), patient characteristics (kidney function, age, cardiovascular risk and polypharmacy because of multiple disorders) and the pre-diabetic state. METHODS: In order to ascertain the opinion of the experts (primary care physicians and other specialists with experience in the management of this type of patient) we conducted a Delphi study to evaluate the consensus rate on diverse aspects related to the diabetogenicity of different statins, and the factors that influence their choice. RESULTS: Consensus was highly significant concerning aspects such as the varying diabetogenicity profiles of different statins, as some of them do not significantly worsen glucose metabolism. There was an almost unanimous consensus that pitavastatin is the safest statin in this regard. CONCLUSIONS: Factors to consider in the choice of a statin regarding its diabetogenicity are the dose and patient-related factors: age, cardiovascular risk, diabetes risk and baseline metabolic parameters (which must be monitored during the treatment), as well as kidney function

Dietary α-linolenic acid, marine ω-3 fatty acids, and mortality in a population with high fish consumption: Findings from the PREvención con DIeta MEDiterránea (PREDIMED) Study

12 Páginas.-- 6 Tablas.-- 1 FiguraBackground-Epidemiological evidence suggests a cardioprotective role of α-linolenic acid (ALA), a plant-derived ω-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all-cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long-chain n-3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results-We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable-adjusted Cox regressionmodels were fitted to estimate hazard ratios. ALA intake correlated towalnut consumption (r=0.94). During a 5.9-y follow-up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios formeeting ALArecommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56-0.92) for all-causemortality and 0.95 (95% CI 0.58-1.57) for fatal cardiovascular disease. The hazard ratios formeeting the recommendation for long-chain n-3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67-1.05) for all-causemortality, 0.61 (95% CI 0.39-0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29-0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22-1.01) for sudden cardiac death. The highest reduction in all-cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45-0.87]). Conclusions-In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all-cause mortality, whereas protection from cardiac mortality is limited to fish-derived long-chain n-3 polyunsaturated fatty acids.This study was funded in part by Instituto de Salud Carlos III (ISCIII) (Spanish Ministry of Economy) through grants RTIC G03/140, RTIC RD 06/0045, Centro Nacional de Investigaciones Cardiovasculares CNIC 06/2007, ISCIII FIS PS09/01292, the Spanish Ministry of Science and Innovation (MICINN) AGL2010‐22319‐C03‐02 and AGL2009‐13906‐C02‐02, and an unrestricted grant from the California Walnut Commission. Sala‐Vila holds a Miguel Servet I fellowship from the Ministry of Economy and Competitiveness through the ISCIII

Potato consumption does not increase blood pressure or incident hypertension in 2 cohorts of Spanish adults

5 TablasBackground: Potatoes have a high glycemic load but also antioxidants, vitamins, and minerals. It is unclear what mechanisms are involved in relation to their effect on blood pressure (BP) and hypertension. Objectives: This study aimed to assess the association between potato consumption, BP changes, and the risk of hypertension in 2 Spanish populations. Methods: Separate analyses were performed in PREDIMED (PREvención con DIeta MEDiterránea), a multicenter nutrition intervention trial of adults aged 55-80 y, and the SUN (Seguimiento Universidad de Navarra) project, a prospective cohort made up of university graduates and educated adults with ages (means±SDs) of 42.7±13.3 y for men and 35.1± 10.7 y for women. In PREDIMED, generalized estimating equations adjusted for lifestyle and dietary characteristics were used to assess changes in BP across quintiles of total potato consumption during a 4-y follow-up. Controlled BP values (systolic BP < 140 mm Hg and diastolic BP < 90 mm Hg) during follow-up were also assessed. For SUN, multivariateadjusted HRs for incident hypertension during a mean 6.7-y follow-up were calculated. Results: In PREDIMED, the total potato intake was 81.9 ± 40.6 g/d. No overall differences in systolic or diastolic BP changes were detected based on consumption of potatoes. For total potatoes, the mean difference in change between quintile 5 (highest intake) and quintile 1 (lowest intake) in systolic BP after multivariate adjustment was 20.90 mm Hg (95% CI: -2.56, 0.76 mm Hg; P-trend = 0.1) and for diastolic BP was 20.02 mm Hg (95% CI: -0.93, 0.89 mm Hg; P-trend = 0.8). In SUN, the total potato consumption was 52.7 ± 33.6 g/d, and no significant association between potato consumption and hypertension incidence was observed in the fully adjusted HR for total potato consumption (quintile 5 compared with quintile 1: 0.98; 95% CI: 0.80, 1.19; P-trend = 0.8). Conclusions: Potato consumption is not associated with changes over 4 y in blood pressure among older adults in Spain or with the risk of hypertension among Spanish adults.Supported by the official funding agency for biomedical research of the Spanish Government, Instituto de Salud Carlos III through grants provided to research networks specifically developed for the trial (RTIC G03/140, to RE; RTIC RD 06/0045, to MAM-G) and through Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional [Proyecto de Investigación (PI) 04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505 and PI13/00462], Ministerio de Ciencia e Innovación [Recursos y teconologia agroalimentarias (AGL)-2009-13906-C02 and AGL2010-22319-C03 and AGL2013-49083-C3-1-R], Fundación Mapfre 2010, the Consejería de Salud de la Junta de Andalucía (PI0105/2007), the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana [Generalitat Valenciana Ayuda Complementaria (GVACOMP) 06109, GVACOMP2010-181, GVACOMP2011-151], Conselleria de Sanitat y AP; Atención Primaria (CS) 2010-AP-111 and CS2011-AP-042, and Regional Government of Navarra (P27/2011)