Browsing by MeSH term "Triglycerides"
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Publication Adipose tissue fatty acid chain length and mono-unsaturation increases with obesity and insulin resistance(Nature Publishing Group, 2015-12) Yew Tan, Chong; Virtue, Samuel; Murfitt, Steven; Robert, Lee D; Phua, Yi Hui; Dale, Martin; Griffin, Julian L; Tinahones, Francisco; Scherer, Philipp E; Vidal-Puig, Antonio; [Yew Tan,C; Virtue,S; Dale,M; Vidal-Puig,A] University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, MDU MRC. Addenbrooke´s Hospital, Cambridge, UK. [Murfitt,S; Robert,LD; Phua,YH; Griffin,JL] University of Cambridge Department of Biochemistry, Cambridge, UK. [Tinahones,FJ] UGC Endocrinologia y Nutrición (IBIMA), Hospital Virgen de la Victoria. CIBER of Physiopathology, Obesity and Nutrition (CIBEROBN) Málaga, Spain. [Scherer,P] Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. [Vidal-Puig,A] Wellcome Trust Sanger Institute, Hinxton, Uk. [Robert,LD; Griffin,JL] Medical Research Council - Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, Uk.The non-essential fatty acids, C18:1n9, C16:0, C16:1n7, C18:0 and C18:1n7 account for over 75% of fatty acids in white adipose (WAT) triacylglycerol (TAG). The relative composition of these fatty acids (FA) is influenced by the desaturases, SCD1-4 and the elongase, ELOVL6. In knock-out models, loss of SCD1 or ELOVL6 results in reduced ?9 desaturated and reduced 18-carbon non-essential FA respectively. Both Elovl6 KO and SCD1 KO mice exhibit improved insulin sensitivity. Here we describe the relationship between WAT TAG composition in obese mouse models and obese humans stratified for insulin resistance. In mouse models with increasing obesity and insulin resistance, there was an increase in scWAT ?9 desaturated FAs (SCD ratio) and FAs with 18-carbons (Elovl6 ratio) in mice. Data from mouse models discordant for obesity and insulin resistance (AKT2 KO, Adiponectin aP2-transgenic), suggested that scWAT TAG Elovl6 ratio was associated with insulin sensitivity, whereas SCD1 ratio was associated with fat mass. In humans, a greater SCD1 and Elovl6 ratio was found in metabolically more harmful visceral adipose tissue when compared to subcutaneous adipose tissue.Publication Artery Wall Assessment Helps Predict Kidney Transplant Outcome(Public Library of Science (PLOS), 2015-06-12) Hernández, Domingo; Triñanes, Javier; Salido, Eduardo; Pitti, Sergio; Rufino, Margarita; González-Posada, José Manuel; Torres, Armando; [Hernández,D] Nephrology Department, Carlos Haya Regional University Hospital and University of Málaga (IBIMA), REDinREN, Málaga, Spain. [Triñanes,J; Salido,E] Research Unit, Hospital Universitario de Canarias, Tenerife, Spain. [Pitti,S] Radiology Department, Hospital Universitario de Canarias, Tenerife, Spain. [Rufino,M; González-Posada,JM; Torres,A] Nephrology Department, Hospital Universitario de Canarias, CIBICAN, University of La Laguna, Instituto Reina Sofía de Investigación Renal (IRSIN), Tenerife, Spain.Background: Kidney transplant recipients have high cardiovascular risk, and vascular inflammation may play an important role. We explored whether the inflammatory state in the vessel wall was related to carotid intima-media thickness (c-IMT) and patient survival following kidney transplantation. Methods: In this prospective observational cohort study we measured c-IMT and expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery in 115 kidney transplant candidates. Another c-IMT measurement was done 1-year post-transplantation in 107. By stepwise multiple regression analysis we explored factors associated with baseline c-IMT and their changes over time. Multivariate Cox regression analysis was constructed to identify risk factors for mortality. Results: A worse cardiovascular profile (older age, smoker, diabetic, carotid plaque, systolic blood pressure and vascular calcification) and higher VCAM-1 levels were found in patients in the highest baseline c-IMT tertile, who also had a worse survival. Factors independently related to baseline c-IMT were age (?=0.369, P<0.0001), fasting glucose (?=0.168, P=0.045), smoking (?=0.228, P=0.003) and VCAM-1 levels (?=0.244, P=0.002). Independent factors associated with c-IMT measurement 1-year post-transplantation were baseline c-IMT (?=-0.677, P<0.0001), post-transplant diabetes (?=0.225, P=0.003) and triglycerides (?=0.302, P=0.023). Vascular VCAM-1 levels were associated with increased risk of mortality in bivariate and multivariate Cox regression. Notably, nearly 50% of patients showed an increase or maintenance of high c-IMT 1 year post-transplantation and these patients experienced a higher mortality (13 versus 3.5%; P=0.021). Conclusion: A worse cardiovascular profile and a higher vascular VCAM-1 protein levels at time of KT are related to subclinical atheromatosis. This could lead to a higher post-transplant mortality. Pre-transplant c IMT, post-transplant diabetes and triglycerides at 1-year post-transplantation may condition a high c-IMT measurement post-transplantation, which may decrease patient survival.Publication Artery Wall Assessment Helps Predict Kidney Transplant Outcome.(Public Library of Science (PLOS), 2015-06-12) Hernández, Domingo; Triñanes, Javier; Salido, Eduardo; Pitti, Sergio; Rufino, Margarita; González-Posada, José Manuel; Torres, Armando; [Hernández,D] Nephrology Department, Carlos Haya Regional University Hospital and University of Málaga (IBIMA), REDinREN, Málaga, Spain. [Triñanes,J; Salido,E] Research Unit, Hospital Universitario de Canarias, Tenerife, Spain. [Pitti,S] Radiology Department, Hospital Universitario de Canarias, Tenerife, Spain. [Rufino,M; González-Posada,JM; Torres,A] Nephrology Department, Hospital Universitario de Canarias, CIBICAN, University of La Laguna, Instituto Reina Sofía de Investigación Renal (IRSIN), Tenerife, Spain.BACKGROUND: Kidney transplant recipients have high cardiovascular risk, and vascular inflammation may play an important role. We explored whether the inflammatory state in the vessel wall was related to carotid intima-media thickness (c-IMT) and patient survival following kidney transplantation. METHODS: In this prospective observational cohort study we measured c-IMT and expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery in 115 kidney transplant candidates. Another c-IMT measurement was done 1-year post-transplantation in 107. By stepwise multiple regression analysis we explored factors associated with baseline c-IMT and their changes over time. Multivariate Cox regression analysis was constructed to identify risk factors for mortality. RESULTS: A worse cardiovascular profile (older age, smoker, diabetic, carotid plaque, systolic blood pressure and vascular calcification) and higher VCAM-1 levels were found in patients in the highest baseline c-IMT tertile, who also had a worse survival. Factors independently related to baseline c-IMT were age (β=0.369, P<0.0001), fasting glucose (β=0.168, P=0.045), smoking (β=0.228, P=0.003) and VCAM-1 levels (β=0.244, P=0.002). Independent factors associated with c-IMT measurement 1-year post-transplantation were baseline c-IMT (β=-0.677, P<0.0001), post-transplant diabetes (β=0.225, P=0.003) and triglycerides (β=0.302, P=0.023). Vascular VCAM-1 levels were associated with increased risk of mortality in bivariate and multivariate Cox regression. Notably, nearly 50% of patients showed an increase or maintenance of high c-IMT 1 year post-transplantation and these patients experienced a higher mortality (13 versus 3.5%; P=0.021). CONCLUSION: A worse cardiovascular profile and a higher vascular VCAM-1 protein levels at time of KT are related to subclinical atheromatosis. This could lead to a higher post-transplant mortality. Pre-transplant c IMT, post-transplant diabetes and triglycerides at 1-year post-transplantation may condition a high c-IMT measurement post-transplantation, which may decrease patient survival.Publication Association between blood marker analyses regarding physical fitness levels in Spanish older adults: A cross-sectional study from the PHYSMED project(Public Library of Science (PLOS), 2018-10-24) Aparicio-Ugarriza, Raquel; Diaz, Angel Enrique; Palacios, Gonzalo; Bibiloni Esteva, Maria Del Mar; Julibert, Alicia; Tur, Josep A; Gonzalez-Gross, MarcelaBiomarkers have been postulated as essential variables to measure the effects of exercise on the human body. To investigate the relationship between physical fitness (PF) and blood biomarkers that are associated with disease risk in Spanish older adults, four hundred and twenty-nine adults (57% females) aged older than 55 years from a cross-sectional study were included. A battery of PF test was performed, and participants were divided into 3 groups: low, medium and high fitness. Blood samples were collected, and subjects were also grouped based on a particular biomarker being within its reference range. Furthermore, drug intake and dietary intake were considered for each participant. Higher concentrations out of the reference range were observed for vitamin 25(OH)D (67.9%) and total cholesterol (TC) (58.6%). Participants from the low PF group presented lower significant concentrations out of the reference range for vitamin B-12 and triglycerides; however, participants in the low PF group showed higher significant concentrations out of the reference range for total homocysteine, creatinine, TC, HDL-cholesterol and LDL-cholesterol (LDL-c) than those in the high PF group (all p<0.05). Considering drugs related to blood lipid modifications, subjects who regularly consumed lipid reducers presented higher significant concentrations out of the reference range for TC and LDL-c than participants who did not take these drugs (p<0.01). Participants from the high PF group presented better blood marker profiles, namely, lower blood markers related to disease risk out of the reference range. These blood markers could be used as a routine method for considering PF groups in older adults.Publication Association of adiponectin (ADIPOQ) rs2241766 polymorphism and dyslipidemia in HIV/HCV-coinfected patients(Wiley, 2014-05) Pineda-Tenor, Daniel; Berenguer, Juan; Garcia-Broncano, Pilar; Jimenez-Sousa, Maria Angeles; Fernandez-Rodriguez, Amanda; Diez, Cristina; Garcia-Alvarez, Monica; Carrero, Ana; Catalán, Pilar; Aldámiz-Echevarria, Teresa; Resino, Salvador; Instituto de Salud Carlos III; RETICS-Sida (RIS-ISCIII) (España); Fundación para la Investigación y la Prevención del Sida en EspañaBackground: The adiponectin (ADIPOQ) rs2241766 polymorphism is related to metabolic abnormalities. The aim of this study was to evaluate the association of the ADIPOQ rs2241766 polymorphism with serum dyslipidemia and insulin resistance (IR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. Methods: We carried out a cross-sectional study on 262 patients. ADIPOQ rs2241766 polymorphisms were genotyped by GoldenGate® assay. Generalized linear models (GLMs) were used to compare continuous outcome variables (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and homeostatic model assessment (HOMA)) and categorical outcome variables (TC≥200 mg/dL, TG≥170 mg/dL, LDL-C≥100 mg/dL, HDL-C≤35 mg/dL, non-HDL-C≥120 mg/dL and HOMA≥3·8) according to ADIPOQ genotype under a dominant inheritance model. Results: Patients with the rs2241766 GG/GT genotype had significantly lower serum TC levels (P=0·038) and percentages of TC≥200 mg/dL (P=0·022) than rs2241766 TT carriers. When adjusted GLM was performed, rs2241766 GG/GT was associated with low serum TC levels (arithmetic mean ratio (AMR)=0·92 [(95% CI=0·85; 0·99) P=0·024]) and low likelihood of TC≥200 mg/dL (odds ratio (OR)=0·32 [(95% CI=0·11; 0·88) P=0·027]. When stratifying by steatosis, no significant values were found for patients without steatosis. However, for patients with steatosis, rs2241766 GG/GT genotypes were related to low TC serum values of TC (AMR=0·89; P=0·027), LDL-C (AMR=0·85; P=0·039) and non-HDL-C (AMR=0·86; P=0·015). No significant associations were found between rs2241766 and HOMA values. Conclusions: The presence of the ADIPOQ rs2241766 G allele (GG/GT genotype) was associated with a protective effect against dyslipidemia, primarily in HIV/HCV-coinfected patients with steatosis.Publication Associations between Both Lignan and Yogurt Consumption and Cardiovascular Risk Parameters in an Elderly Population: Observations from a Cross-Sectional Approach in the PREDIMED Study(Elsevier, 2017-04) Creus-Cuadros, Anna; Tresserra-Rimbau, Anna; Quifer-Rada, Paola; Angel Martinez-Gonzalez, Miguel; Corella, Dolores; Salas-Salvao, Jordi; Fito, Montserrat; Estruch, Ramon; Gomez-Gracia, Enrique; Lapetra, Jose; Aros, Fernando; Ros, Emili; Serra-Majem, Lluis; Pinto, Xavier; Jose Moreno, Juan; Ruiz-Canela, Miguel; Vicente Sorli, Jose; Basora, Josep; Schroeder, Helmut; Maria Lamuela-Raventos, Rosa; PREDIMED Study InvestigatorsBackground The study of dietary patterns is gaining interest. Although the health benefits of yogurt and lignans have been investigated separately, to our knowledge there are no studies on their associative effects. Objective The aim of this study was to evaluate a possible association between yogurt and lignans using biomarkers of cardiovascular disease risk in an elderly population. Design We conducted a cross-sectional analysis of the association between baseline dietary information and cardiovascular risk parameters using food frequency questionnaires. Participants We enrolled 7,169 Spanish participants of the PREDIMED (Prevencion con Dieta Mediterranea) study (elderly men and women at high cardiovascular risk) from June 2003 to June 2009. Main outcome measures Cardiovascular risk parameters, including cholesterol, tri-glycerides, glucose, body mass index, weight, waist circumference, and blood pressure were measured. Statistical analysis General linear models were used to assess the relationship between categorical variables (yogurt, total dairy intake, lignans, and yogurt plus lignans) and cardiovascular risk parameters. Results The consumption of either yogurt or lignans seems to have beneficial effects on human health, but the consumption of both showed greater improvement in some cardiovascular health parameters. Indeed, participants with a higher consumption of both yogurt and lignans showed lower total cholesterol (estimated beta-coefficients= -6.18; P=0.001) and low-density lipoprotein cholesterol levels (beta=-4.92; P=0.005). In contrast, participants with lower yogurt and lignan consumption had a higher body mass index (beta=0.28; P=0.007) and weight (beta=1.20; P=0.008). Conclusions High lignan and yogurt consumption is associated with a better cardiovascular risk parameters profile in an elderly Mediterranean population. Further research is warranted to determine the mechanisms and consequences of this potential effect.Publication Decreased GPIHBP1 protein levels in visceral adipose tissue partly underlie the hypertriglyceridemic phenotype in insulin resistance.(2018-11-08) Surendran, R Preethi; Udayyapan, Shanti D; Clemente-Postigo, Mercedes; Havik, Stefan R; Schimmel, Alinda W M; Tinahones, Fransisco; Nieuwdorp, Max; Dallinga-Thie, Geesje MGPIHBP1 is a protein localized at the endothelial cell surface that facilitates triglyceride (TG) lipolysis by binding lipoprotein lipase (LPL). Whether Glycosyl Phosphatidyl Inositol high density lipoprotein binding protein 1 (GPIHBP1) function is impaired and may underlie the hyperTG phenotype observed in type 2 diabetes is not yet established. To elucidate the mechanism underlying impaired TG homeostasis in insulin resistance state we studied the effect of insulin on GPIHBP1 protein expression in human microvascular endothelial cells (HMVEC) under flow conditions. Next, we assessed visceral adipose tissue GPIHBP1 protein expression in type 2 diabetes Lepr db/db mouse model as well as in subjects with ranging levels of insulin resistance. We report that insulin reduces the expression of GPIHBP1 protein in HMVECs. Furthermore, GPIHBP1 protein expression in visceral adipose tissue in Lepr db/db mice is significantly reduced as is the active monomeric form of GPIHBP1 as compared to Leprdb/m mice. A similar decrease in GPIHBP1 protein was observed in subjects with increased body weight. GPIHBP1 protein expression was negatively associated with insulin and HOMA-IR. In conclusion, our data suggest that decreased GPIHBP1 availability in insulin resistant state may hamper peripheral lipolysis capacity.Publication Effect of alirocumab on individuals with type 2 diabetes, high triglycerides, and low high-density lipoprotein cholesterol.(2020-02-08) Colhoun, Helen M; Leiter, Lawrence A; Müller-Wieland, Dirk; Cariou, Bertrand; Ray, Kausik K; Tinahones, Francisco J; Domenger, Catherine; Letierce, Alexia; Israel, Marc; Samuel, Rita; Del Prato, StefanoMixed dyslipidemia [elevated non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TGs), and decreased HDL-C] is common in type 2 diabetes mellitus (T2DM) and is associated with increased cardiovascular risk. Non-HDL-C and apolipoprotein B (ApoB) are the preferred therapeutic targets for mixed dyslipidemia. Alirocumab is a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) that effectively reduces low-density lipoprotein cholesterol (LDL-C), non-HDL-C, ApoB, and lipoprotein(a) (Lp[a]), and is well-tolerated in individuals with T2DM. The previously reported open-label ODYSSEY DM-DYSLIPIDEMIA trial data demonstrated the effects of alirocumab on individuals with non-HDL-C ≥ 100 mg/dL and TGs ≥ 150 and Alirocumab significantly reduced non-HDL-C [LS mean difference (standard error (SE)), - 35.0% (3.9)], ApoB [LS mean difference (SE), - 34.7% (3.6)], LDL-C [LS mean difference (SE), - 47.3% (5.2)], LDL particle number [LS mean difference (SE), - 40.8% (4.1)], and Lp(a) [LS mean difference (SE), - 29.9% (5.4)] versus usual care from baseline to Week 24 (all P Alirocumab is an effective therapeutic option for individuals with T2DM, TGs ≥ 200 mg/dL, and HDL-CPublication Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMED-Plus study(2019-12-23) Galmes-Panades, Aina M; Varela-Mato, Veronica; Konieczna, Jadwiga; Wärnberg, Julia; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Corella, Dolores; Schröder, Helmut; Vioque, Jesús; Alonso-Gómez, Ángel M; Martínez, J Alfredo; Serra-Majem, Luís; Estruch, Ramon; Tinahones, Francisco J; Lapetra, José; Pintó, Xavier; Tur, Josep A; Garcia-Rios, Antonio; Riquelme-Gallego, Blanca; Gaforio, José Juan; Matía-Martín, Pilar; Daimiel, Lidia; Micó Pérez, Rafael Manuel; Vidal, Josep; Vázquez, Clotilde; Ros, Emilio; Garcia-Arellano, Ana; Díaz-López, Andrés; Asensio, Eva M; Castañer, Olga; Fiol, Francisca; Mira-Castejón, Luis Alfredo; Moreno Rodríguez, Anai; Benavente-Marín, Juan Carlos; Abete, Itziar; Tomaino, Laura; Casas, Rosa; Barón López, F Javier; Fernández-García, José Carlos; Santos-Lozano, José Manuel; Galera, Ana; Mascaró, Catalina M; Razquin, Cristina; Papandreou, Christopher; Portoles, Olga; Pérez-Vega, Karla Alejandra; Fiol, Miguel; Compañ-Gabucio, Laura; Vaquero-Luna, Jessica; Ruiz-Canela, Miguel; Becerra-Tomás, Nerea; Fitó, Montserrat; Romaguera, DoraBackground: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Methods: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m(2)) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had >= 3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Results: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05). Conclusions: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health.Publication Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: The ESCARVAL-RISK study.(Public Library of Science (PLOS), 2017-10-18) Orozco-Beltran, Domingo; Gil-Guillen, Vicente F; Redon, Josep; Martin-Moreno, Jose M; Pallares-Carratala, Vicente; Navarro-Perez, Jorge; Valls-Roca, Francisco; Sanchis-Domenech, Carlos; Fernandez-Gimenez, Antonio; Perez-Navarro, Ana; Bertomeu-Martinez, Vicente; Cordero, Alberto; Pascual de la Torre, Manuel; Trillo, Jose L; Carratala-Munuera, Concepcion; Pita-Fernandez, Salvador; Uso, Ruth; Durazo-Arvizu, Ramon; Cooper, Richard S; Sanz, Gines; Castellano, Jose Maria; Ascaso, Juan F; Carmena, Rafael; Tellez-Plaza, MariaThe potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with all-cause mortality and hospitalization due to cardiovascular events in a high-risk population. This prospective registry included high risk adults over 30 years old free of cardiovascular disease (2008-2012). Diagnosis of hypertension, dyslipidemia or diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated. Primary endpoints were all-cause mortality and hospital admission due to coronary heart disease or stroke. We estimated adjusted rate ratios (aRR), absolute risk differences and population attributable risk associated with adverse lipid profiles. 51,462 subjects were included with a mean age of 62.6 years (47.6% men). During an average follow-up of 3.2 years, 919 deaths, 1666 hospitalizations for coronary heart disease and 1510 hospitalizations for stroke were recorded. The parameters that showed an increased rate for total mortality, coronary heart disease and stroke hospitalization were, respectively, low HDL-Cholesterol: aRR 1.25, 1.29 and 1.23; high Total/HDL-Cholesterol: aRR 1.22, 1.38 and 1.25; and high Triglycerides/HDL-Cholesterol: aRR 1.21, 1.30, 1.09. The parameters that showed highest population attributable risk (%) were, respectively, low HDL-Cholesterol: 7.70, 11.42, 8.40; high Total/HDL-Cholesterol: 6.55, 12.47, 8.73; and high Triglycerides/HDL-Cholesterol: 8.94, 15.09, 6.92. In a population with cardiovascular risk factors, HDL-cholesterol, Total/HDL-cholesterol and triglycerides/HDL-cholesterol ratios were associated with a higher population attributable risk for cardiovascular disease compared to other common biomarkers.Publication Lixisenatida en pacientes con diabetes tipo 2 y obesidad: más allá del control glucémico(Elsevier, 2017-05) Roca-Rodríguez, M Mar; Muros de Fuentes, María Teresa; Piédrola-Maroto, Gonzalo; Quesada-Charneco, Miguel; Maraver-Selfa, Silvia; Tinahones, Francisco J; Mancha-Doblas, Isabel; [Roca-Rodríguez,MM] UGC de Endocrinología y Nutrición, Hospital Universitario Puerta del Mar, Cádiz, España. [Muros de Fuentes,MT; Piédrola-Maroto,G] UGC de Endocrinología y Nutrición, Hospital Virgen de las Nieves, Granada, España. [Quesada-Charneco,M] UGC de Endocrinología y Nutrición, Hospital San Cecilio, Granada, España. [Maraver-Selfa,S; Tinahones,FJ; Mancha-Doblas,I] UGC de Endocrinología y Nutrición, Hospital Clínico Universitario Virgen de la Victoria. Hospital Regional Universitario, Málaga, España. [Tinahones,FJ] Instituto de Investigación Biomédica de Málaga (IBIMA), Complejo Hospitalario de Málaga (Virgen de la Victoria)/Universidad de Málaga; CIBER Pathophysiology of Obesity and Nutrition (CB06/03), Málaga, España.[ES] Objetivo: Evaluar la tolerancia a lixisenatida y sus efectos sobre el peso y el control metabólico de pacientes con diabetes tipo 2 y obesidad. Diseño: ˜Estudio prospectivo. Emplazamiento: Consultas de atención especializada de Endocrinología y Nutrición en Almería, Granada y Málaga. Participantes: Pacientes con diabetes tipo 2 y obesidad. Intervenciones: Respuesta y tolerancia al tratamiento con lixisenatida. Mediciones principales: Se analizaron datos clínicos y analíticos con medidas de cambio intrasujeto antes-después del tratamiento. Resultados: Evaluamos 104 pacientes (51% mujeres) con diabetes tipo 2 y obesidad (Almería 18,3%; Granada 40,4%; Málaga 41,3%). Edad media 58,4 ± 10,5 anos ˜ y duración media de diabetes 11,2 ± 6,7 anos. ˜ El tiempo medio desde la visita basal a la revisión tras inicio de tratamiento con lixisenatida fue de 3,8 ± 1,6 meses. Encontramos mejoría significativa del peso (p < 0,001)índice de masa corporal (p < 0,001), circunferencia de cintura (p = 0,002), presión arterial sistólica (p < 0,001) y diastólica (p = 0,001), glucemia en ayunas (p < 0,001), HbA1c (p = 0,022), colesterol total (p < 0,001), colesterol LDL (p = 0,046) y triglicéridos (p = 0,020). No se observó alteración de cifras de amilasa en relación con el tratamiento con lixisenatida, y el 7,9% no lo toleraron. Conclusiones: Lixisenatida consigue: 1) mejoría significativa de parámetros antropométricos ycontrol glucémico (glucemia basal y HbA1c); 2) descenso significativo de la presión arterial y del perfil lipídico, y 3) seguridad y buena tolerancia en la mayoría de los pacientes. Además, encontramos una significativa intensificación del tratamiento antihipertensivo e hipolipemiante. [EN] Aim: To evaluate tolerance to lixisenatide and its effects on weight and metabolic control in type2 diabetes and obese patients. Design: Prospective study. Setting: Endocrinology clinics in Almeria, Granada and Malaga. Participants: Patients with type2 diabetes and obesity. Interventions: Response and tolerance to lixisenatide treatment. Main measurements: Clinical and analytical data of the subjects were evaluated at baseline and after treatment. Results: The study included 104 patients (51% women) with type2 diabetes and obesity (Almeria 18.3%; Granada 40.4%; Malaga 41.3%). The mean age was 58.4±10.5years, and the mean duration of diabetes was 11.2±6.7years. The patients were re-evaluated at 3.8±1.6months after treatment with lixisenatide. Significant improvements were found in weight (P<.001), body mass index (P<.001), waist circumference (P=.002), systolic blood pressure (P<.001), diastolic blood pressure (P=.001), fasting glucose (P<.001), HbA1c (P=.022), Total cholesterol (P<.001), LDL-cholesterol (P=.046), triglycerides (P=.020), hypertension drugs (P<.001), and lipids drugs (P<.001). No changes were observed in levels of amylase related to lixisenatide treatment, and 7.9% of patients did not tolerate it. Conclusions: Lixisenatide achieved significant improvements in anthropometric parameters, glycaemic control (fasting glucose and HbA1c), blood pressure and lipids. It was safe and well tolerated in most patients. In addition, there was a significant increase in the use of antihypertensive and lipid-lowering therapy.Publication Long-term intake of a high-protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats(Elsevier, 2017-08) Diaz-Rua, Ruben; Keijer, Jaap; Palou, Andreu; van Schothorst, Evert M; Oliver, PaulaIntake of high-protein (HP) diets has increased over the last years, mainly due to their popularity for body weight control. Liver is the main organ handling ingested macronutrients and it is associated with the beginning of different pathologies. We aimed to deepen our knowledge on molecular pathways affected by long-term intake of an HP diet. We performed a transcriptome analysis on liver of rats chronically fed with a casein-rich HP diet and analyzed molecular parameters related to liver injury. Chronic increase in the dietary protein/carbohydrate ratio up-regulated processes related with amino acid uptake/metabolism and lipid synthesis, promoting a molecular environment indicative of hepatic triacylglycerol (TG) deposition. Moreover, changes in expression of genes involved in acid-base maintenance and oxidative stress indicate alterations in the pH balance due to the high acid load of the diet, which has been linked to liver/health damage. Up-regulation of immune-related genes was also observed. In concordance with changes at gene expression level, we observed increased liver TG content and increased serum markers of hepatic injury/inflammation (aspartate transaminase, C-reactive protein and TNF-alpha). Moreover, the HP diet strongly increased hepatic mRNA and protein levels of HSP90, a marker of liver injury. Thus, we show for the first time that long-term consumption of an HP diet, resulting in a high acid load, results in a hepatic transcriptome signature reflecting increased TG deposition and increased signs of health risk (increased inflammation, alterations in the acid-base equilibrium and oxidative stress). Persistence of this altered metabolic status could have unhealthy consequences.Publication Metabolic profiling and targeted lipidomics reveals a disturbed lipid profile in mothers and fetuses with intrauterine growth restriction.(2018-09-11) Miranda, Jezid; Simões, Rui V; Paules, Cristina; Cañueto, Daniel; Pardo-Cea, Miguel A; García-Martín, María L; Crovetto, Francesca; Fuertes-Martin, Rocio; Domenech, Monica; Gómez-Roig, María D; Eixarch, Elisenda; Estruch, Ramon; Hansson, Stefan R; Amigó, Nuria; Cañellas, Nicolau; Crispi, Fatima; Gratacós, EduardFetal growth may be impaired by poor placental function or maternal conditions, each of which can influence the transfer of nutrients and oxygen from the mother to the developing fetus. Large-scale studies of metabolites (metabolomics) are key to understand cellular metabolism and pathophysiology of human conditions. Herein, maternal and cord blood plasma samples were used for NMR-based metabolic fingerprinting and profiling, including analysis of the enrichment of circulating lipid classes and subclasses, as well as the number of sub-fraction particles and their size. Changes in phosphatidylcholines and glycoproteins were prominent in growth-restricted fetuses indicating significant alterations in their abundance and biophysical properties. Lipoprotein profiles showed significantly lower plasma concentrations of cholesterol-intermediate density lipoprotein (IDL), triglycerides-IDL and high-density lipoprotein (HDL) in mothers of growth-restricted fetuses compared to controls (pPublication National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio: a pooled analysis of 458 population-based studies in Asian and Western countries(Oxford University Press, 2020-02) NCD Risk Factor CollaborationBackground: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and nonHDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries. Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group. Results: Since similar to 1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at similar to 0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as similar to 0.7 per decade in Swiss men (equivalent to similar to 26% decline in coronary heart disease risk per decade). The ratio increased in China. Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol.Publication Oxidized LDL Is Associated With Metabolic Syndrome Traits Independently of Central Obesity and Insulin Resistance(American Diabetes Association (ADA), 2017-02) Hurtado-Roca, Yamilee; Bueno, Hector; Fernandez-Ortiz, Antonio; Ordovas, Jose M; Ibáñez, Borja; Fuster, Valentin; Rodríguez-Artalejo, Fernando; Laclaustra, Martin; Centro Nacional de Investigaciones Cardiovasculares Carlos III (España); Banco Santander; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Instituto de Salud Carlos III; Ministerio de Economía y Competitividad (España); Fundación ProCNIC; Ministerio de la Producción (Perú)This study assesses whether oxidative stress, using oxidized LDL (ox-LDL) as a proxy, is associated with metabolic syndrome (MS), whether ox-LDL mediates the association between central obesity and MS, and whether insulin resistance mediates the association between ox-LDL and MS. We examined baseline data from 3,987 subjects without diabetes in the Progression of Early Subclinical Atherosclerosis (PESA) Study. For the second, third, and fourth ox-LDL quartiles versus the first, the odds ratios (95% CI) for MS were 0.84 (0.52, 1.36), 1.47 (0.95, 2.32), and 2.57 (1.66, 4.04) (P < 0.001 for trend) once adjusted for age, sex, smoking, LDL-cholesterol, BMI, waist circumference, and HOMA-insulin resistance (HOMA-IR). Results showing the same trend were found for all MS components except glucose concentration. Ox-LDL mediated 13.9% of the association of waist circumference with triglycerides and only 1-3% of the association with HDL-cholesterol, blood pressure, and insulin concentration. HOMA-IR did not mediate the association between ox-LDL and MS components. This study found higher ox-LDL concentrations were associated with MS and its components independently of central obesity and insulin resistance. Ox-LDL may reflect core mechanisms through which MS components develop and progress in parallel with insulin resistance and could be a clinically relevant predictor of MS development.Publication Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context.(Frontiers Media, 2015-03-27) Rivera, Patricia; Bindila, Laura; Pastor, Antoni; Pérez-Martín, Margarita; Pavón, Francisco-Javier; Serrano, Antonia; de la Torre, Rafael; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan; [Rivera,P; Pavón,FJ; Serrano,A; Rodríguez de Fonseca,F; Suárez,J] UGC Salud Mental, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga, Málaga, Spain. [Rivera,P; Pavón,FJ; Serrano,A; de la Torre,R; Rodríguez de Fonseca,F; Suárez,J] CIBER OBN, Instituto de Salud Carlos III, Madrid, Spain. [Bindila,L, Lutz,B] Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany. [Pastor,A; de la Torre,R] Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Spain. [Pastor,A] Facultat de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain. [Pérez-Martín,M] Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga, Málaga, Spain. [de la Torre, R] Facultat de Ciencies de la Salut i de la Vida, Universitat Pompeu Fabra (CEXS-UPF), Barcelona, Spain.Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)), astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3(+) and BrdU(+) subgranular cells as well as GFAP(+), Iba1(+) and cleaved caspase-3(+) cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3(+), GFAP(+) and 3-weeks-old BrdU(+) cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context.Publication Physicochemical Properties of Lipoproteins Assessed by Nuclear Magnetic Resonance as a Predictor of Premature Cardiovascular Disease. PRESARV-SEA Study(Multidisciplinary Digital Publishing Institute (MDPI), 2021-03-29) Fernández-Cidón, Bárbara; Candás-Estébanez, Beatriz; Gil-Serret, Miriam; Amigó, Núria; Corbella, Emili; Rodríguez-Sánchez, M. Ángeles; Padró-Miquel, Ariadna; Brotons, Carlos; Hernández-Mijares, Antonio; Calmarza, Pilar; Jarauta, Estibaliz; Brea, Angel J.; Mauri, Marta; Guijarro, Carlos; Vila, Àlex; Valdivielso, Pedro; Corbella, Xavier; Pintó, Xavier; [Fernández-Cidón,B; Candás-Estébanez,B; Padró-Miquel,A] Bioquímica Especial y Biología Molecular, Laboratori Clínic, Hospital Universitario de Bellvitge, L’Hospitalet de Ll., Spain. [Candás-Estébanez,B] Clinical Laboratory, SCIAS-Hospital de Barcelona, Barcelona, Spain. [Gil-Serret,M; Amigó,N] Biosfer Teslab, Reus, Spain. [Amigó,N] CIBERDEM, Universidad Rovira i Virgili, Tarragona, Spain. [Corbella,E; Rodríguez-Sánchez,MA; Corbella,X; Pintó,X] Unidad de Lípidos y Riesgo Vascular, Servicio de Medicina Interna, Hospital Universitario de Bellvitge-IDIBELL, Barcelona, Spain. [Corbella,E; Pintó,X] Centro de Investigación Biomédica en Red, Fisiopatologia de la Obesidad y Nutrición CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Brotons,C] EAP Sardenya, Instituto de Investigaciones Biomédicas Sant Pau, Barcelona, Spain. [Hernández-Mijares,A] Hospital Universitario Dr. Peset, Valencia, Spain. [Calmarza,P; Jarauta,E] Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, CIBERCV IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain. [Brea,AJ] Hospital General San Pedro, Logroño, Spain. [Mauri,M] Hospital de Terrassa (Consorci Sanitari de Terrassa), Terrassa, Spain. [Guijarro,C] Departamento de Esepecialidades Médicas y Salud Pública, Unidad de Medicina Interna, Hospital Universitario Fundación Alcorcón, Universidad Rey Juan Carlos, Alcorcón, Spain. [Vila,A] Hospital de Figueres (Fundació Salut Empordà), Figueres, Spain. [Valdivielso,P] Hospital Universitario Virgen de la Victoria, IBIMA, Universidad de Málaga, Málaga, Spain. [Corbella,X] Facultad de Medicina y Ciencias de la Salud, Universitat Internacional de Catalunya, Barcelona, Spain. [Pintó,X] Department of Medicine, Campus Bellvitge, Universidad de Barcelona, L’Hospitalet de Ll., Spain.Some lipoprotein disorders related to the residual risk of premature cardiovascular disease (PCVD) are not detected by the conventional lipid profile. In this case-control study, the predictive power of PCVD of serum sdLDL-C, measured using a lipoprotein precipitation method, and of the physicochemical properties of serum lipoproteins, analyzed by nuclear magnetic resonance (NMR) techniques, were evaluated. We studied a group of patients with a first PCVD event (n = 125) and a group of control subjects (n = 190). Conventional lipid profile, the size and number of Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) particles, and the number of particles of their subclasses (large, medium, and small) were measured. Compared to controls, PCVD patients had lower concentrations of all LDL particles, and smaller and larger diameter of LDL and HDL particles, respectively. PCVD patients also showed higher concentrations of small dense LDL-cholesterol (sdLDL), and triglycerides (Tg) in LDL and HDL particles (HDL-Tg), and higher concentrations of large VLDL particles. Multivariate logistic regression showed that sdLDL-C, HDL-Tg, and large concentrations of LDL particles were the most powerful predictors of PCVD. A strong relationship was observed between increased HDL-Tg concentrations and PCVD. This study demonstrates that beyond the conventional lipid profile, PCVD patients have other atherogenic lipoprotein alterations that are detected by magnetic resonance imaging (MRI) analysis.Publication Postprandial Apolipoprotein B48 is Associated with Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis(Multidisciplinary Digital Publishing Institute (MDPI), 2020-08-02) Mena-Vázquez, Natalia; Rojas-Gimenez, Marta; Jimenez Nuñez, Francisco Gabriel; Manrique-Arija, Sara; Rioja, José; Ruiz-Limón, Patricia; Ureña, Inmaculada; Castro-Cabezas, Manuel; Valdivielso, Pedro; Fernández-Nebro, Antonio; [Mena-Vázquez,N; Jimenez Nuñez,FG; Manrique-Arija,S; Rioja,J; Ruiz-Limón,P; Ureña,I; Valdivielso,P; Fernández-Nebro,A] The Institute of Biomedical Research in Malaga (IBIMA), Málaga, Spain. [Mena-Vázquez,N; Jimenez Nuñez,FG; Manrique-Arija,S; Ureña,I; Fernández-Nebro,A] UGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, Spain. [Rojas-Gimenez,M] UGC de Reumatología, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, Córdoba, Spain. [Rioja,J; Valdivielso,P; Fernández-Nebro,A] Departamento de Medicina y Dermatología, Universidad de Málaga, Málaga, Spain. [Ruiz-Limón,P] Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Clínico Virgen de la Victoria, Málaga, Spain. [Castro-Cabezas,M] Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands. [Valdivielso,P] UGC de Medicina Interna, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.Objective: To describe postprandial lipemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis measured as carotid intima-media thickness (cIMT). Methods: We performed an observational study of 40 patients with RA and 40 sex and age-matched controls. Patients with dyslipidemia were excluded. Pathologically increased cIMT was defined as a carotid thickness greater than the 90th percentile (>p90) for age and sex. Fasting and postprandial plasma lipids, cholesterol, triglycerides, apolipoprotein B48 (ApoB48), and total ApoB were evaluated. The other variables included were clinical and laboratory values, Framingham score, and the 28-joint Disease Activity Score (DAS28). Two multivariate models were constructed to identify factors associated with pathologic cIMT in patients with RA. Results: Fasting lipid values were similar in patients with RA and controls, although those of postprandial ApoB48 were higher (median (IQR), 14.4 (10.8–12.1) vs. 12.1 (2.3–9,8); p = 0.042). Pathologic cIMT was recorded in 10 patients with RA (25%) and nine controls (22.5%). In patients with RA, pathologic cIMT was associated with postprandial ApoB48 (OR (95% CI), 1.15 (1.0–1.3)) and total ApoB (OR [95% CI], 1.12 [1.1–1.2]). The second model revealed a mean increase of 0.256 mm for cIMT in patients with elevated anticitrullinated protein antibodies (ACPAs). Conclusion: Postprandial ApoB48 levels in patients with RA are higher than in controls. Postprandial ApoB48 and total ApoB levels and markers of severity, such as ACPAs, are associated with pathologic cIMT in patients with RA. Our findings could indicate that these atherogenic particles have a negative effect on the endothelium.Publication Prevalence of Premorbid Metabolic Syndrome in Spanish Adult Workers Using IDF and ATPIII Diagnostic Criteria: Relationship with Cardiovascular Risk Factors(Public Library of Science (PLOS), 2014-02-20) Tauler, Pedro; Bennasar-Veny, Miquel; Morales-Asencio, Jose M.; López-González, Angel Arturo; Vicente-Herrero, Teofila; de Pedro-Gómez, Joan Ernest; Royo, Vanessa; Pericas-Beltran, Jordi; Aguilo, AntoniBackground: Metabolic Syndrome (MetS) is a complex disorder defined as a cluster of interconnected risk factors such as hypertension, dyslipidemia, obesity and high blood glucose levels. Premorbid metabolic syndrome (PMetS) is defined by excluding patients with previously diagnosed cardiovascular disease or diabetes mellitus from those suffering MetS. We aimed to determine the prevalence of PMetS in a working population, and to analyse the relationship between the diagnostic criteria of the International Diabetes Federation (IDF) and of the National Cholesterol Education Program Adult Treatment Panel III (ATPIII). The relationship between the presence of PMetS and cardiovascular risk factors was also analysed. Research Methodology/Findings: A cross-sectional study was conducted in 24,529 male and 18,736 female Spanish (white western European) adult workers (20-65 years) randomly selected during their work health periodic examinations. Anthropometrics, blood pressure and serum parameters were measured. The presence of MetS and PMetS was ascertained using ATPIII and IDF criteria. Cardiovascular risk was determined using the Framingham-REGICOR equation. The results showed MetS had an adjusted global prevalence of 12.39% using ATPIII criteria and 16.46% using IDF criteria. The prevalence of PMetS was slightly lower (11.21% using ATPIII criteria and 14.72% using IDF criteria). Prevalence in males was always higher than in females. Participants with PMetS displayed higher values of BMI, waist circumference, blood pressure, glucose and triglycerides, and lower HDL-cholesterol levels. Logistic regression models reported lower PMetS risk for females, non-obese subjects, non-smokers and younger participants. Cardiovascular risk determined with Framingham-REGICOR was higher in participants with PMetS. Conclusions: PMetS could be a reliable tool for the early identification of apparently healthy individuals who have a significant risk for developing cardiovascular events and type 2 diabetes.Publication Repositioning of the global epicentre of non-optimal cholesterol(Nature Publishing Group, 2020-06-04) NCD Risk Factor Collaboration (NCD-RisC); Frontera-Juan, Guillem; Ramos-Asensio, Rafael; Reigada Mendez, Rebeca; Romaguera, Dora; Torrent Quetglas, MatiesHigh blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.