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1. Prehypertension A Meta-Analysis of the Epidemiology, Risk Factors, and Predictors of Progression

Author: Guo, Xiaofan, Zou, Liling, Zhang, Xingang, Li, Jue, Zheng, Liqiang, Sun, Zhaoqing, Hu, Jian, Wong, Nathan D., and Sun, Yingxian
Subjects: Adult, blood glucose/analysis, blood pressure, body mass index, cholesterol, HDL/blood, cholesterol, LDL/blood, cross-sectional studies, disease susceptibility, hypertension/diagnosis/epidemiology/etiology/prevention & control, longitudinal studies, meta-analysis, obesity, prehypertension/epidemiology/etiology/prevention & control, prevalence, risk factors, triglycerides/blood, waist circumference
Abstract: We investigated the prevalence and risk factors of prehypertension, as well as the predictors of progression from prehypertension to hypertension. To do this, we performed a systematic review and meta-analysis of cross-sectional and longitudinal studies, after unrestricted searches of PubMed and The Cochrane Library through September 2010. In addition, we reviewed references, major textbooks, and review articles. Pooled prevalence, standardized mean differences, and odds ratios were estimated by using a random-effects model.Twenty-six articles met our inclusion criteria; these included 20 cross-sectional and 6 longitudinal studies, with a total sample of 250,741 individuals. The overall pooled prevalence of prehypertension was 36%. The pooled prevalence among males was higher than that among females (40% vs 33%). The pooled standardized mean difference for body mass index was 1.37 (95% confidence interval [CI], 1.20–1.55); for total cholesterol, 8.08 (95% CI, 6.71–9.46); for low-density-lipoprotein cholesterol, 5.14 (95% CI, 3.09–7.18); and for fasting plasma glucose, 4.23 (95% CI, 3.28–5.18); all of which showed more significant results in females. The pooled odds ratio was 1.13 (95% CI, 0.93–1.37) for smoking and 0.98 (95% CI, 0.69–1.39) for drinking. In addition, factors such as older age at baseline, male sex, Mongolian race, and being overweight or obese were predictors of progression to hypertension, according to descriptive analysis.The prevalence of prehypertension was relatively high, especially for males. There were many modifiable risk factors associated with prehypertension, to which healthcare providers should pay more attention.
Published: 2011

2. Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease

Author: Arjen J. Cupido, Laurens F. Reeskamp, Aroon D. Hingorani, Chris Finan, Folkert W. Asselbergs, G. Kees Hovingh, Amand F. Schmidt, Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Amsterdam Cardiovascular Sciences, Experimental Vascular Medicine, and ACS - Heart failure & arrhythmias
Subjects: Male, Proprotein Convertase 9/genetics, Coronary Artery Disease/genetics, Genetic Variation, Cholesterol, LDL, Coronary Artery Disease, Mendelian Randomization Analysis, Middle Aged, Cholesterol Ester Transfer Proteins, LDL/blood, Macular Degeneration, Cholesterol, Cholesterol, LDL/blood, Diabetes Mellitus, Type 2, Diabetes Mellitus, Humans, Female, Proprotein Convertase 9, Cardiology and Cardiovascular Medicine, Type 2, Cholesterol Ester Transfer Proteins/genetics
Abstract: IMPORTANCE: Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents. OBJECTIVE: To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes. DESIGN, SETTING, AND PARTICIPANTS: Two-sample 2 × 2 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry. EXPOSURES: Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease. MAIN OUTCOMES AND MEASURES: Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis. RESULTS: Data for 425 354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229 399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P = .34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P = .83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19). CONCLUSIONS AND RELEVANCE: Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.
Published: 2022

3. Comparison Between Non-High-Density Lipoprotein Cholesterol and Low-Density Lipoprotein Cholesterol to Estimate Cardiovascular Risk Using a Multivariate Model.

Author: Palazón-Bru, Antonio, Carbayo-Herencia, Julio Antonio, Simarro-Rueda, Marta, Artigao-Ródenas, Luis Miguel, Divisón-Garrote, Juan Antonio, Molina-Escribano, Francisca, Ponce-García, Isabel, and Gil-Guillén, Vicente Francisco
Subjects: AGE factors in disease, CARDIOVASCULAR diseases, CARDIOVASCULAR diseases risk factors, CHOLESTEROL, COMPARATIVE studies, CONFIDENCE intervals, STATISTICAL correlation, HIGH density lipoproteins, LOW density lipoproteins, MULTIVARIATE analysis, RESEARCH funding, STATISTICAL sampling, SURVIVAL analysis (Biometry), DATA analysis software, DESCRIPTIVE statistics, MANN Whitney U Test
Abstract: Background: Although studies exist comparing low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (HDL-C) in the development of cardiovascular disease (CVD), most have limitations in the mathematical models used to evaluate their prognostic power adjusted for the other risk factors (cardiovascular risk). Objective: The aim of this study was to compare LDL-C and non-HDL-C in patients with CVD to determine whether both parameters predict CVD similarly. Methods: A cohort of 1322 subjects drawn from the general population of a Spanish region was followed between 1992 and 2006. The outcome was time to CVD. Secondary variables were gender, age, hypertension, diabetes, personal history of CVD, current smoker, body mass index, LDL-C, and non-HDL-C. Two CVD prediction models were constructed with the secondary variables, with only the lipid parameter varying (non-HDL-C or LDL-C). In the construction of the models, the following were considered: multiple imputation, events per variable of 10 or more, and continuous predictors as powers. The validation was conducted by bootstrapping obtaining the distribution of the C statistic (discrimination) and the probabilities observed by smooth curves. These results were compared in both models using graphical and analytical testing. Results: There were a total of 137 CVD events. The models showed no differences in the distributions of the C statistic (discrimination, P = .536) or in the calibration plot. Conclusions: In our population, LDL-C and non-HDL-C were equivalent at predicting CVD. More studies using this methodology are needed to confirm these results. [ABSTRACT FROM AUTHOR]
Published: 2018
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4. Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration

Subjects: Male, Magnetic Resonance Spectroscopy, genetic structures, European Continental Ancestry Group/statistics & numerical data, Risk Factors, Cholesterol Ester Transfer Proteins/blood, 80 and over, Odds Ratio, Humans, Metabolomics, European Union, Macular Degeneration/blood, Polymorphism, Aged, Single Nucleotide, Middle Aged, Lipid Metabolism, eye diseases, LDL/blood, Triglycerides/blood, Cholesterol, Cross-Sectional Studies, HDL/blood, lipids (amino acids, peptides, and proteins), Female, sense organs
Abstract: PURPOSE: Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. DESIGN: Pooled analysis of cross-sectional data. PARTICIPANTS: Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. METHODS: AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. MAIN OUTCOME MEASURES: AMD features and stage; lipid measurements. RESULTS: HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14-1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91-0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10-1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10-7), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10-6 and P = 1.6 × 10-4). CONCLUSIONS: Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered.
Published: 2019

5. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study

Subjects: Cohort Studies, Cholesterol, Blood Glucose/metabolism, Genetic Variation/genetics, Proprotein Convertase 9/genetics, Randomized Controlled Trials as Topic/methods, Case-Control Studies, Genetic Predisposition to Disease/genetics, Diabetes Mellitus, Humans, Mendelian Randomization Analysis/methods, LDL/blood, Type 2/blood
Abstract: BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. METHODS: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m2, -0·09 to 0·30). INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins. FUNDING: British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.
Published: 2017

6. The association between exposure to different aspects of shift work and metabolic risk factors in health care workers, and the role of chronotype

Author: Piet Beekhof, Linda W. M. van Kerkhof, Bette Loef, Karin I. Proper, Allard J. van der Beek, Debbie van Baarle, Public and occupational health, and APH - Societal Participation & Health
Subjects: Male, Epidemiology, Physiology, Social Sciences, Biochemistry, Metabolic Diseases/diagnosis, Occupational safety and health, Body Mass Index, Shift work, 0302 clinical medicine, Sociology, Risk Factors, Medicine and Health Sciences, Medicine, Public and Occupational Health, Non-U.S. Gov't, education.field_of_study, Multidisciplinary, Research Support, Non-U.S. Gov't, Shift Work Schedule, Middle Aged, C-Reactive Proteins, Lipids, 030210 environmental & occupational health, Hospitals, Body Fluids, LDL/blood, Circadian Rhythm, Triglycerides/blood, C-Reactive Protein, Blood, Cholesterol, Cholesterol, LDL/blood, Social Systems, Female, Anatomy, Waist Circumference, Research Article, Adult, Waist, Science, Health Personnel, Population, Research Support, Cholesterol/blood, C-Reactive Protein/analysis, 03 medical and health sciences, Metabolic Diseases, Journal Article, Humans, education, Triglycerides, Occupational Health, business.industry, Shift Work Schedule/psychology, Case-control study, Biology and Life Sciences, Proteins, Chronotype, Cholesterol, LDL, Physical Activity, Anthropometry, Medical Risk Factors, Case-Control Studies, Physiological Processes, Sleep, business, Body mass index, 030217 neurology & neurosurgery, Demography
Abstract: Objective Shift work has been linked to cardio-metabolic diseases, but insight into different shift work-related aspects and chronotype of shift workers and their relation with metabolic risk factors is limited. This study examined the association between current shift work status, frequency and duration of night shift work, chronotype, and metabolic risk factors in a population of health care workers. Methods Anthropometrics, questionnaires, and blood samples were collected from 503 shift working and 93 non-shift working health care workers employed in hospitals. Body mass index, waist circumference, cholesterol (total, HDL, LDL), triglycerides, and high-sensitivity C-reactive protein were measured. Associations of current shift work, frequency (non-night shift worker, 1–2, 3–4, ≥5 night shifts/month) and duration of night shift work (non-night shift workers
Published: 2019

7. Association of Triglyceride-Lowering LPL Variants and LDL-C–Lowering LDLR Variants With Risk of Coronary Heart Disease

Author: Adam S. Butterworth, Deepak L. Bhatt, Alberico L. Catapano, Angela M. Wood, Chris J. Packard, Ulrich Laufs, Marc S. Sabatine, Stephen J. Nicholls, John J.P. Kastelein, Clare Oliver-Williams, John Danesh, Kausik K. Ray, Brian A. Ference, Henry N. Ginsberg, M. John Chapman, Emanuele Di Angelantonio, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Pulmonary hypertension & thrombosis, Oliver-Williams, Clare [0000-0002-3573-2426], Wood, Angela [0000-0002-7937-304X], Butterworth, Adam [0000-0002-6915-9015], Di Angelantonio, Emanuele [0000-0001-8776-6719], Danesh, John [0000-0003-1158-6791], and Apollo - University of Cambridge Repository
Subjects: Male, Apolipoprotein B, Blood lipids, Coronary Disease, SECONDARY PREVENTION, THERAPY, 01 natural sciences, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Loss of Function Mutation, Risk Factors, Receptors, Receptors, LDL/genetics, WIDE ASSOCIATION, 030212 general & internal medicine, Prospective Studies, 11 Medical and Health Sciences, Original Investigation, biology, General Medicine, Middle Aged, LDL/blood, Triglycerides/blood, Cholesterol, Cholesterol, LDL/blood, Low-density lipoprotein, Female, lipids (amino acids, peptides, and proteins), Life Sciences & Biomedicine, Metabolic Networks and Pathways, medicine.medical_specialty, INHIBITION, LDL/genetics, Lower risk, 03 medical and health sciences, Medicine, General & Internal, Coronary Disease/blood, General & Internal Medicine, Internal medicine, medicine, Humans, Lipoprotein Lipase/genetics, Genetic Predisposition to Disease, 0101 mathematics, CARDIOVASCULAR EVENTS, METAANALYSIS, Triglycerides, Apolipoproteins B, GEMFIBROZIL, Science & Technology, DENSITY-LIPOPROTEIN-CHOLESTEROL, Triglyceride, business.industry, 010102 general mathematics, Genetic Variation, Cholesterol, LDL, Odds ratio, Mendelian Randomization Analysis, Apolipoproteins B/blood, REDUCTION, Lipoprotein Lipase, ATHEROSCLEROSIS, Receptors, LDL, chemistry, Case-Control Studies, biology.protein, business, Lipoprotein
Abstract: Importance: Triglycerides and cholesterol are both carried in plasma by apolipoprotein B (ApoB)-containing lipoprotein particles. It is unknown whether lowering plasma triglyceride levels reduces the risk of cardiovascular events to the same extent as lowering low-density lipoprotein cholesterol (LDL-C) levels. Objective: To compare the association of triglyceride-lowering variants in the lipoprotein lipase (LPL) gene and LDL-C-lowering variants in the LDL receptor gene (LDLR) with the risk of cardiovascular disease per unit change in ApoB. Design, Setting, and Participants: Mendelian randomization analyses evaluating the associations of genetic scores composed of triglyceride-lowering variants in the LPL gene and LDL-C-lowering variants in the LDLR gene, respectively, with the risk of cardiovascular events among participants enrolled in 63 cohort or case-control studies conducted in North America or Europe between 1948 and 2017. Exposures: Differences in plasma triglyceride, LDL-C, and ApoB levels associated with the LPL and LDLR genetic scores. Main Outcomes and Measures: Odds ratio (OR) for coronary heart disease (CHD) - defined as coronary death, myocardial infarction, or coronary revascularization - per 10-mg/dL lower concentration of ApoB-containing lipoproteins. Results: A total of 654783 participants, including 91129 cases of CHD, were included (mean age, 62.7 years; 51.4% women). For each 10-mg/dL lower level of ApoB-containing lipoproteins, the LPL score was associated with 69.9-mg/dL (95% CI, 68.1-71.6; P = 7.1 × 10 -1363 ) lower triglyceride levels and 0.7-mg/dL (95% CI, 0.03-1.4; P =.04) higher LDL-C levels; while the LDLR score was associated with 14.2-mg/dL (95% CI, 13.6-14.8; P = 1.4 × 10 -465 ) lower LDL-C and 1.9-mg/dL (95% CI, 0.1-3.9; P =.04) lower triglyceride levels. Despite these differences in associated lipid levels, the LPL and LDLR scores were associated with similar lower risk of CHD per 10-mg/dL lower level of ApoB-containing lipoproteins (OR, 0.771 [95% CI, 0.741-0.802], P = 3.9 × 10 -38 and OR, 0.773 [95% CI, 0.747-0.801], P = 1.1 × 10 -46 , respectively). In multivariable mendelian randomization analyses, the associations between triglyceride and LDL-C levels with the risk of CHD became null after adjusting for differences in ApoB (triglycerides: OR, 1.014 [95% CI, 0.965-1.065], P =.19; LDL-C: OR, 1.010 [95% CI, 0.967-1.055], P =.19; ApoB: OR, 0.761 [95% CI, 0.723-0.798], P = 7.51 × 10 -20 ). Conclusions and Relevance: Triglyceride-lowering LPL variants and LDL-C-lowering LDLR variants were associated with similar lower risk of CHD per unit difference in ApoB. Therefore, the clinical benefit of lowering triglyceride and LDL-C levels may be proportional to the absolute change in ApoB.
Published: 2019

8. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author: Chris Finan, Yoav Ben-Shlomo, Eric B. Larson, Tine Jess, Richard W Morris, Daniel I. Chasman, Fernando Pires Hartwig, Catherine Welch, Rodney J. Scott, Helen E. Speedy, Andrzej Pajak, Raha Pazoki, André G. Uitterlinden, Torben Hansen, Marc Sanson, Hakon Hakonarson, Claudia Langenberg, Joey Ward, John Wright, Dorothée Thuillier, Ben Kinnersley, Diederick E. Grobbee, Yvonne T. van der Schouw, Pieter Sonneveld, Michiel L. Bots, Harold Snieder, Karim Labreche, Dan M. Roden, Archie Campbell, Melissa C. Smart, Christine Power, Pim van der Harst, Amélie Bonnefond, Ingrid E. Christophersen, Riyaz S. Patel, Uwe Völker, Stephen Hancock, Niels Grarup, Dennis O. Mook-Kanamori, Mariza de Andrade, Caroline Dale, N. Charlotte Onland-Moret, David R. Crosslin, Meena Kumari, Erik Ingelsson, Michael V. Holmes, Spiros Denaxas, Sudha Seshadri, Kees Hovingh, Marcus Dörr, Paul M. Ridker, Stefan Coassin, Albert Hofman, Andrew N. Nicolaides, Oluf Pedersen, Philippe Froguel, Simonetta Guarrera, Murray H. Brilliant, Sara E. Dobbins, Salim Yusuf, Kari Hemminki, Erik P A Van Iperen, Abbas Dehghan, Jill P. Pell, Alexander Teumer, Peter W. Schofield, Aroon D. Hingorani, Dan Mason, Amand F. Schmidt, Rui Bebiano Da Providencia E Costa, James M. Allan, Leslie A. Lange, Niels Weinhold, Stefan Gustafsson, Jackie F. Price, Mika Kivimäki, Hynek Pikhart, Kirchner H. Lester, Lars Lind, Philip J. Law, Cara L. Carty, David Preiss, Richard S. Houlston, Robin Young, Tom W. Meade, Martin O'Donnell, Alexander P. Reiner, Ni Li, Oscar H. Franco, Zammy Fairhurst-Hunter, Ronan Roussel, Tim Christen, Ilja Demuth, David Carrell, Catherine A. McCarty, Juan P. Casas, Johann Willeit, Peter H. Whincup, Stela McLachlan, Adelaida Sanchez-Galvez, Hartmut Goldschmidt, Guillaume Paré, Harry Hemingway, Anubha Mahajan, Elisabeth Steinhagen-Thiessen, Elizabeth G. Holliday, Giuseppe Matullo, Henry Völzke, Ian Ford, Martin Bobak, Pedro Marques-Vidal, Bertrand Cariou, Bernardo L. Horta, Melissa L. Bondy, Goya Wanamethee, Naveed Sattar, Steve E. Humphries, Marylyn D. Ritchie, Kristina Norman, Carlotta Sacerdote, Giovanni Fiorito, Sebastian E. Baumeister, Amit Sud, Dennis Valentine, Andreas Engert, Juri Demuth, Rupert Faraway, Abdonas Tamosiunas, Andrie G. Panayiotou, Terrie Kitchner, Lars Bertram, Sandosh Padmanabhan, Sofia Malyutina, Anke H. Maitland-van der Zee, Alex J. Cornish, Joshua C. Denny, Jian'an Luan, Robert A. Scott, Daniel I. Swerdlow, John Attia, Karin Willeit, Gareth J. Morgan, Michael Chong, Ruben N. Eppinga, Elina Hyppönen, Ekaterina V. Baranova, Jackie A. Cooper, Ghazaleh Fatemifar, Niek Verweij, Max Moldovan, Brendan J. Keating, M. Abdullah Said, Markus M. Lerch, Christina M. Lill, Markus Hansson, Jemma C. Hopewell, Björn Nilsson, Folkert W. Asselbergs, Ruzena Kubinova, Molly Went, Nicholas J. Wareham, Stefan Kiechl, Yanchun Bao, Allan Linneberg, Matthias Simon, Epidemiology and Data Science, Pulmonology, Paediatric Pulmonology, APH - Personalized Medicine, AII - Inflammatory diseases, AII - Cancer immunology, CCA - Cancer biology and immunology, Ear, Nose and Throat, Schmidt, Amand F, Holmes, Michael V, Preiss, David, Swerdlow, Daniel I, Hypponen, Elina, Dehghan, Abbas, Schmidt, Amand F [0000-0003-1327-0424], Apollo - University of Cambridge Repository, Lifelines Cohort, ICBP Consortium, METASTROKE Consortium of the ISGC, PharmacoTherapy, -Epidemiology and -Economics, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Schmidt, Amand F. [0000-0003-1327-0424], Epidemiology, and Hematology
Subjects: Oncology, lcsh:Diseases of the circulatory (Cardiovascular) system, Genetic association studies, Proprotein Convertase 9/genetics, Apolipoprotein B, Anticholesteremic Agents/adverse effects, Myocardial Infarction, Blood lipids, Genome-wide association study, 030204 cardiovascular system & hematology, Coronary artery disease, Gastroenterology, Medical and Health Sciences, Stroke/epidemiology, Brain Ischemia, 0302 clinical medicine, Risk Factors, Dyslipidemias/blood, Medicine, LDL-cholesterol, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, Myocardial infarction, Mendelian randomisation, 1102 Cardiorespiratory Medicine and Haematology, Randomized Controlled Trials as Topic, Kardiologi, biology, Anticholesteremic Agents, PCSK9 Inhibitors, Single Nucleotide, 16. Peace & justice, LDL/blood, 3. Good health, Stroke, Cholesterol, Treatment Outcome, Cholesterol, LDL/blood, ICBP Consortium, Phenome-wide association scan, Proprotein Convertase 9, Cardiology and Cardiovascular Medicine, Research Article, medicine.medical_specialty, Serine Proteinase Inhibitors, Down-Regulation, 610 Medicine & health, Single-nucleotide polymorphism, Placebo, Polymorphism, Single Nucleotide, Risk Assessment, 03 medical and health sciences, Internal medicine, Genetic variation, Myocardial Infarction/epidemiology, Humans, Serine Proteinase Inhibitors/adverse effects, Polymorphism, Dyslipidemias, Genetic association, Lifelines Cohort authors, METASTROKE Consortium of the ISGC, business.industry, PCSK9, Cholesterol, LDL, Odds ratio, medicine.disease, Cardiovascular System & Hematology, lcsh:RC666-701, biology.protein, Brain Ischemia/epidemiology, Clinical Medicine, business, Biomarkers, Biomarkers/blood, Genome-Wide Association Study
Abstract: BackgroundWe characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9.MethodsPublished and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Fourteen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentrationResultsThe PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95%CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95%CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95%CI 0.57; 1.22) for the GS, compared to 0.85 (95%CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95%CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable.ConclusionsGenetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. Apparent discordance between genetic associations and trial outcome for T2DM might be explained lack by a of statistical precision, or differences in the nature and duration of genetic versus pharmacological perturbation of PCSK9.FundingThis research was funded by the British Heart Foundation (SP/13/6/30554, RG/10/12/28456, FS/18/23/33512), UCL Hospitals NIHR Biomedical Research Centre, by the Rosetrees and Stoneygate Trusts.Condensed abstractEvidence on the long-term efficacy and safety of therapeutic inhibition of PCSK9 is lacking. To explore potential long-term effects of PCSK9 inhibition, we characterised the phenotypic consequence of LDL-cholesterol lowering variants at the PCSK9 locus. A PCSK9 gene score comprising 4 SNPs recapitulated the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and risk of myocardial infarction, and was associated with an increased risk of type 2 diabetes. No associations with safety outcomes such as cancer, COPD, Alzheimer’s disease or atrial fibrillation were identified. Our findings suggest PCSK9 inhibition may be safe and effective during prolonged use.
Published: 2019

9. Shaping of Peripheral T Cell Responses by Lymphatic Endothelial Cells

Author: Stéphanie Hugues, Juan Dubrot, and Marion Humbert
Subjects: 0301 basic medicine, Aging/metabolism/pathology, Apolipoproteins E/genetics/metabolism, Review, ddc:616.07, Inbred C57BL, immunomodulation, Mice, 0302 clinical medicine, lymphatic endothelial cells, Immunology and Allergy, tolerance, biology, Cell biology, LDL/blood, Fatty Acids/metabolism, Triglycerides/blood, medicine.anatomical_structure, Cholesterol, Atherosclerosis/metabolism/pathology, peripheral tissue antigens, Lymphatic Vessels/metabolism/pathology, Macrophages/metabolism/pathology, T cell, Knockout, Antigen presentation, Immunology, Dendritic Cells/metabolism/pathology, Connexins/genetics/metabolism, 03 medical and health sciences, Immune system, Endothelial Cells/metabolism/pathology, MHC class I, Collagen/metabolism, Lymph node stromal cell, medicine, Animals, Antigen-presenting cell, MHC class II, Animal, fungi, Cell Movement/physiology, Diet, T-Lymphocytes/metabolism/pathology, High-Fat, antigen presentation, 030104 developmental biology, Disease Models, biology.protein, CD8, 030215 immunology
Abstract: Lymph node stromal cells (LNSCs) have newly been promoted to the rank of new modulators of T cell responses. The different non-hematopoietic cell subsets in lymph node (LN) were considered for years as a simple scaffold, forming routes and proper environment for antigen (Ag)-lymphocyte encountering. Deeper characterization of those cells has recently clearly shown their impact on both dendritic cell and T cell functions. In particular, lymphatic endothelial cells (LECs) control lymphocyte trafficking and homeostasis in LNs and limit adaptive immune responses. Therefore, the new role of LECs in shaping immune responses has drawn the attention of immunologists. Striking is the discovery that LECs, among other LNSCs, ectopically express a large range of peripheral tissue-restricted Ags (PTAs), and further present PTA-derived peptides through major histocompatibility class I molecules to induce self-reactive CD8(+) T cell deletional tolerance. In addition, both steady-state and tumor-associated LECs were described to be capable of exogenous Ag cross-presentation. Whether LECs can similarly impact CD4(+) T cell responses through major histocompatibility class II restricted Ag presentation is still a matter of debate. Here, we review and discuss our current knowledge on the contribution of Ag-presenting LECs as regulators of peripheral T cell responses in different immunological contexts, including autoimmunity and cancer.
Published: 2017
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10. Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Author: Ridker, P. M., Revkin, J., Amarenco, P., Brunell, R., Civeira, F., Flather, M., Glynn, R. J., Gregoire, J., Jukema, J. W., Karpov, Y., Kastelein, J. J. P., Koenig, W., Lorenzatti, A., Manga, P., Masiukiewicz, U., Miller, M., Mosterd, A., Murin, J., Nicolau, J. C., Nissen, S., Ponikowski, P., Santos, R. D., Schwartz, P. F., Soran, H., White, H., Wright, R. S., Vrablik, M., Yunis, C., Shear, C. L., Tardif, Conde D, J. -C., Colquhoun, D, Missault, L, Grégoire, J, Gao, R, Urina, M, Solar, M, Jensen, Hk, Grobbee, D, Savolainen, M, Schiele, Fn, Montalescot, G, Edes, I, Blake, G, Lotan, C, Maggioni, A, Savonitto, S, Lee, Cw, Leiva Pons JL, Dan, Ga, Cortada, Jb, Mellbin, L, Kahan, T, Noble, S, Hwang, Jj, Sritara, P, Tökgozoğlu, L, Tarasenko, L, Borer, Js, Black, H, Carmena, R, Furie, Kl, Mcmurray, J, Neaton, J, Zannad, F, O’Neill, B, Welty, F, Mcnamara, R, Chun, H, Abbott, Jd, Jacoby, D, Mcpherson, C, Jadbabaie, F, Pinto, D, Mccullough, L, Silverman, Ie, Sansing, Lh, Dearborn-Tomazos, J, Foody, J, Schindler, J, Piazza, G, Chakrabarti, A, Pride, Y, Gelfand, E, Baultrukonis, D, Chaudhuri, S, Frederich, R, Johnson, M, Mridha, K, Powell, C, Wang, E, Wei, C, Anderson, P, Buonanno, M, Epsley, C, Evans, B, Frolova, M, Goetsch, M, Hessinger, D, Ikehara, E, Ivanac, K, Kizko, J, Le, K, McNally-Dufort, C, Morocco, T, Nadkarni, S, Nissen, T, Nye, R, Pak, R, Pence, D, Redifer, P, Schwartz, W, Sattler, C, Schade, R, Sullivan, B, Wegner, J, Alvarez, Ca, Budassi, N, Vogel, Dr, Avaca, H, Conde, Dg, Estol, Cc, Gelersztein, E, Glenny, Ja, Hershson, Ar, Bruno, Rl, Maffei, Le, Soler, Jm, Zaidman, Cj, Carnero, Gs, Colombo, Hr, Jure, Ho, Luquez, Ha, Ramos, Hr, Resk, Jh, Rusculleda, Mm, Ulla, Mr, Caccavo, A, Farias, Ef, Wenetz, Lm, Cabella, Pr, Cuadrado, Ja, Chahin, M, Mackinnon, Ij, Zarandon, Rb, Schmidberg, J, Fernandez, Aa, Montana, O, Codutti, Or, Gorosito, Vm, Maldonado, N, Sala, J, De La Fuente RA, Casabella, Te, Di Gennaro JP, Guerrero, Ra, Alvarez, Ms, Berli, M, Botta, Ce, Montenegro, Ee, Vico, Ml, Begg, A, Lehman, R, Gilfillan, Cp, D'Emden, M, Markovic, Tp, Sullivan, D, Aroney, C, Stranks, Sn, Crimmins, Ds, Arstall, M, Van Gaal, W, Davis, T, Aylward, Pe, Amerena, J, William, M, Proietto, J, Purnell, Pw, Singh, B, Arya, Kw, Dart, Am, Thompson, P, Davis, Sm, Carroll, Pa, De Looze, F, Jayasinghe, R, Bhindi, R, Buysschaert, I, Sarens, T, van de Borne, P, Scott, Bp, Roosen, J, Cools, F, Missault, Lh, Debroye, C, Schoors, Df, Hollanders, G, Schroe, Hh, De Sutter, J, Hermans, K, Carlier, M, van Landegem, P, Verwerft, J, Mulleners, T, Delforge, Md, Soufflet, V, Elegeert, I, Descamps, Os, Janssens, S, Lemmens, Rc, Desfontaines, P, Scheen, A, Heijmans, S, Capiau, L, Vervoort, G, Carlier, Sg, Faes, D, Alzand, B, Keuleers, S, De Wolf, L, Thoeng, J, De Bruyne, L, de Santos MO, Felicio, Js, Areas, Ca, Figueiredo, El, Michalaros, Yl, Neuenschwander, Fc, Reis, G, Saad, Ja, Kormann, Ap, Nascimento, Cv, Precoma, Db, Abib, E Jr, dos Santos FR, Mello, Yg, Saraiva, Jf, Rech, Rl, Cerci, R, Fortes, Ja, Rossi, Pr, de Lima, e Silva FA, Hissa, M, Silva, Rp, de Souza WK, Guimarães Filho FV, Mangili, Oc, de Oliveira Paiva MS, Tumelero, R, Abrantes, Ja, Caramori, Pr, Dutra, Op, Leaes, Pe, Manenti, Er, Polanczyk, Ca, Bandeira, e Farias FA, de Moraes Junior JB, Russo, La, Alves AR Jr, Dracoulakis, Md, Ritt, Le, Saporito, Wf, Herdy, Ah, Maia, Ln, Sternieri, Mv, Ayoub, Jc, Bianco, Ht, da Costa FA, Eliaschewitz, Fg, Fonseca, Fa, Nakandakare, Er, Bonansea, Tc, Castro, Nm, de Barros, e Silva PG, Smith, P, Botelho, Rv, Resende, Es, Barbieri, Ds, Hernandes, Me, Bajaj, H, Beaudry, P, Berlingieri, Jc, Salter, Tj, Ajala, B, Anderson, Tj, Nanji, A, Ross, S, Pandey, S, Desrosiers, D, Gaudet, D, Moran, G, Csanadi, Ma, St-Amour, E, Cusimano, S, Halperin, Fa, Babapulle, M, Vizel, S, Petrella, J, Spence, Jd, Gupta, N, Tellier, G, Bourgeois, R, Gregóire, Jc, Wesson, T, Zadra, R, Twum-Barima, Dy, Cha, Jy, Hartleib, Mc, Bergeron, J, Chouinard, G, Mcpherson, Tp, Searles, G, Peterson, Sr, Mukherjee, A, Lepage, S, Conway, Jr, Kouz, Sm, Dion, D, Pesant, Y, Cheung, Ss, Goldenberg, Rm, Aronson, R, Gupta, Ak, O’Mahoney, M, Pliamm, L, Teitelbaum, I, Hoag, Gn, Nadra, Ij, Yared, Z, Yao, Lc, Nguyen, T, Saunders, Kk, Potthoff, S, Varleta, P, Assef, V, Godoy, Jg, Olivares, C, Roman, O, Vejar, M, Montecinos, H, Pincetti, C, Li, Y, Wang, D, Li, J, Yang, X, Du, Y, Wang, G, Yang, P, Zhang, X, Xu, P, Zhao, Y, Chen, J, Li, S, Li, W, Zhang, L, Zhu, Y, Zhang, Y, Zhou, C, Wang, Y, Liu, F, Ma, Y, Ti, Z, Zeng, X, Zhou, Y, Cui, G, Li, D, Xue, L, Jiang, J, Lian, Y, He, Y, Mendoza, Ja, Bonfanti, Ja, Dada, Fa, Urina-Triana, Ma, Rodriguez, Wr, Sanchez, Ml, Lozno, Hy, Triana, Eh, Arambula, Rm, Rico-Carrillo, Ae, Gallo, Hj, Catano, Js, Jattin, Fg, Plazas, Ja, Gomez, Je, Botero-Lopez, R, Gomez, Ni, Munoz, Cf, Pelaez, Sv, Eraso, Am, Goyes, Ar, Elbl, L, Fiserova, N, Vesely, J, Wasserburger, B, Blaha, V, Vojacek, J, Maskova, P, Hutyra, M, Vrkoc, J, Hala, T, Vodnansky, P, Bocek, P, Cifkova, R, Bufka, V, Ceska, R, Machkova, M, Zidkova, E, Lukac, M, Mikusova, T, Kellnerova, I, Kuchar, L, Ferkl, R, Cech, V, Zemek, S, Monhart, Z, Davidsen, F, Joensen, A, Lihn, As, Rasmussen, Tk, Wiggers, H, Lindgren, Lm, Schmidt, U, Galatius, S, Sillesen, H, Bronnum Schou, J, Thomsen, Kk, Urhammer, S, Jeppensen, J, Schou, M, May, O, Steffensen, R, Nielsen, Wb, Nielesen, T, Jepsen, Jm, Rai, A, Sykulski, R, Andersen, Lt, Rickers, H, Frost, L, Lomholdt, J, Egstrup, K, Wermuth, S, Klausen, L, Lassus, J, Palomaki, A, Khari, J, Tatlisumak, T, Kekki, S, Vanttinen, E, Strandberg, A, Valtonen, M, Sia, Sm, Nerg, O, Puhakka, M, Strand, J, Timonen, M, Levola, J, Arstila, L, Taurio, J, Kantola, I, Suomi, J, Humaloja, K, Askonen, K, Schiele, F, Sibon, I, Zemour, G, Goube, P, Petit, C, Chati, Z, Range, G, Rabahi, F, Rihani, R, Bergerot, C, Roubille, F, Boye, A, Probst, V, Ferrari, E, Cayla, G, Thouvenot, E, Delarche, N, Couffinhal, T, Coisne, D, Paillard, F, Elbaz, M, Decoulx, E, Angoulvant, D, Agraou, B, Caudmont, S, Berrouschot, J, Lauer, B, Schoell, I, Trenk, D, Derwahl, Km, Khariouzov, A, Proepper, F, Stawowy, P, Da Stephan, U, Stoessel, J, Voehringer, Hf, Dorsel, T, Stellbrink, C, Rinke, A, Northroff, J, Bourhaial, H, Stratmann, M, Wetzel, T, Axthelm, C, Guenzel, A, Weigmann, I, Faghih, M, Hagemann, D, Schaefer, A, Weber, D, Luedemann, J, Contzen, C, Kornmann, Mo, Winkelmann, B, Simon, J, Felix, S, Brauer, C, Laufs, U, Schmidt, E, Marten, I, Licka, M, Heisters, J, Appel, Kf, Kleinecke-Pohl, U, Klein, C, von Hodenberg EF, Maus, O, Sigal, H, Taeschner, H, Schwimmbeck, P, Lemke, B, Perings, C, Illies, G, Pfuetzner, A, Salbach, P, Hengstenberg, C, Kohler, A, Mudra, H, Behnke, T, Baar, M, Jeserich, M, Scholz, G, Naudts, I, Voller, H, Herrmann, Hj, von Engelhardt CB, Gerke, S, Pohlmeier, L, Schaufele, T, Woehrle, J, Al-Zoebi, A, Horacek, T, Peterfai, E, Kemeny, V, Lakatos, F, Bod, E, Andrassy, P, Andreka, P, Balo, T, Davidovits, Z, Laszlo, Z, Nagy, K, Papp, A, Somogyi, A, Toldy-Schedel, E, Vertes, A, Voros, P, Paragh, G, Martyin, T, Hajdu, C, Deak, L, Farago, K, Nagy, A, Kirschner, R, Koszegi, Z, Zilahi, Z, Toth, K, Wittmann, I, Bajcsi, D, Reiber, I, Toth, L, Benczur, B, Nagy, L, Sydo, T, Lupkovics, G, Oroszlan, T, Crean, P, Mahon, Ng, Mcadam, B, Macneill, B, Katz, A, Tsalihin, D, Vazan, A, Eitan, A, Lewis, Bs, Gavish, D, Wainstein, J, Mosenzon, O, Mosseri, M, Vishlitzky, V, Atar, S, Nseir, Wb, Brenner, H, Elis, A, Fuchs, S, Shimon, I, Solodky, A, Goldhaber, A, Tanne, D, Knobler, H, Kracoff, Oh, Hussein, O, Auriel, E, Chorin, E, Sharir, T, Bitzur, R, Shechter, M, Antonicelli, R, Franceschini, E, Porcu, M, Sesti, G, Maggiolini, S, Salvioni, A, Filardi, Pp, Trimarco, B, Averna, M, Pasqualini, L, Pirro, M, Pantaleoni, M, Piovaccari, G, Arca, M, Fedele, Francesco, Roncon, L, Anselmi, M, Sganzerla, P, Morocutti, G, Bonora, E, Dimas, Al, Esperon, Ga, Morales-Villegas, E, Isunza, Jm, Beltran, Lg, Molina, Ca, Garcia, Dk, Ruiz, La, Reyna, Ls, De los Rios Ibarra MO, Soto, Jr, Gonzalez-Ortiz, M, Herrera-Marmolejo, M, Ramos, Sa, Ramos-Lopez, Ga, Stobschinski, Ca, Aguilarsalinas, Ca, Alpizar-Salazar, M, Jimenez-Sanchez, M, Sanchez Mijangos JH, Elizondo Moreno ER, Garcia Castillo, A, Garcia Hernandez PA, Gonzalez-Gonzalez, Jg, Riojas Charles CM, Valdez Lopez HG, Nuriulu Escobar PL, Lechuga Martin del Campo, A, Castro Montes BE, Mendez Bucio, A, Rodriguez-Briones, I, Torre Amione, G, Violante Ortiz, R, Luna Ceballos RI, Lopez Rosas, E, Bax, Wa, Alhakim, M, van de Wiel, A, Liem, Ss, Groutars, Rg, Herrman, Jp, Hovingh, Gk, van de Wetering ML, van Royen, N, Groenemeijer, Be, Hoedemaker, G, Schaap, J, Ronner, E, Angun, M, Mairuhu, At, Van Alem AP, Martens, Fm, Heijmeriks, Ja, van Hal JM, Schoofs, Mw, den Hartog FR, Kentgens, S, Post, Jc, Louwerenburg, Jw, van Rossum, P, Viergever, Ep, Donders, Sh, Kamphuisen, Pw, van Beek, E, Nijmeijer, R, Lenderink, T, Schreuder, T, Kuijper, Af, The, Sh, Van het Hof-Wiersma JJ, Tichelaar, P, Westerndorp, I, Breedveld, Rw, Karalis, I, Romer, Tj, Bogaard, K, Van Koningsbruggen, P, Kroon, Aa, Hoogslag, Pa, Rensing, Bj, Cramer, E, Remmen, Jj, Riksen, Np, Bokern, Mj, Cabezas, Mc, Mulder, H, Nierop, Pr, van Kempen WW, Zoet-Nugteren, Sk, van Daele ME, Swart, Hp, van der Zwaan CT, Hermans, Wr, Magro, M, van de Wal RM, Hassink, Rj, Visseren, F, Veenendaal, A, De Nooijer, C, Troquay, Rp, Imholz, Bp, van der Meer, P, Visser, Rp, van Leendert RJ, Gosselink, Ma, Baker, J, Benatar, Jr, Kerr, J, Pryke, Jr, Scott, Rs, Millar-Corte, Gd, Williams, M, Montgomery, B, Venter, Dj, Ternouth, If, Decaigney, Sc, Hart, Hh, Corin, A, Garden, Pi, Sheahan, D, Harding, Sa, Korecki, J, Supronik, J, Styczkiewicz, M, Bijata-Bronisz, R, Rusicka, T, Walczak, M, Krolikowski, Z, Ostrowski, J, Lukaszewicz, M, Przekwas-Jaruchowska, M, Zieba, B, Miekus, P, Orkwiszewska-Nalewajko, A, Piepiorka, M, Kubalski, P, Wychota, K, Blach, E, Ochala, A, Okopien, B, Wronska, D, Janion, M, Czarnecka, D, Kolodziejczyk, J, Konieczynska, M, Landa, K, Mirek-Bryniarska, E, Necki, M, Pasternak, Da, Rozpondek, P, Trebacz, J, Walczewska, J, Sidor, M, Broncel, M, Drozdz, J, Kosmider, M, Saryusz-Wolska, M, Kucharska, D, Opalinska, E, Pijanowski, Z, Wozniak, I, Banaszkiewicz, K, Klecha, A, Horodecki, M, Piskorz-Wapinska, J, Kobielusz-Gembala, I, Kim, Mh, Kim, Dk, Cho, Br, Kim, Ks, Her, Sh, Lee, Sy, Rhee, My, Kim, K, Kang, Wc, Kim, Dh, Cho, Ys, Kim, Sh, Rim, Sj, Tahk, Sj, Jeon, Hk, Yoon, J, Mociran, M, Pop, Cf, Minescu, B, Andrei, Ld, Radoi, M, Calin, A, Ciomag, Rm, Copaci, I, Fruntelata, Ag, Popescu, M, Tivadar, S, Roman, G, Avram, Ri, Mistodie, Cv, Morosanu, M, Popa, Ar, Popescu, Ml, Popoviciu, Ms, Tase, A, Busegeanu, M, Popescu, A, Szilagyi, I, Sitterli-Natea, Cn, Maximov, Dm, Munteanu, M, Negrisanu, Gd, Kuzin, A, Popov, D, Shapovalova, J, Vishneva, E, Shutemova, E, Pasechnik, E, Bogdanov, E, Khasanov, N, Barbarash, Ol, Shangina, Oa, Tarasov, N, Solonev, O, Kosmacheva, E, Chernyatina, Ma, Ginzburg, M, Blokhin, A, Bulanova, N, Drapkina, Om, Gordeev, Ig, Libov, Ia, Lomakin, N, Panchenko, E, Shogenov, Zs, Zateyshchikov, D, Klein, G, Motylev, I, Belenkiy, Di, Demin, A, Nikolaev, Ky, Oleynikov, V, Zrazhevskiy, K, Katelnitskiy, I, Khaisheva, L, Aksentiev, S, Nedoshivin, A, Popova, Vb, Agafina, As, Ballyuzek, M, Baranova, E, Burova, N, Eryshev, S, Filippov, A, Goloshchekin, Bm, Konstantinov, V, Kostenko, Va, Simanenkov, Vi, Volkova, A, Duplyakov, D, Reshetko, O, Shvarts, Y, Kuznetsov, Va, Samoylova, Yg, Tolkacheva, V, Shalaev, Sv, Khokhlov, Al, Malygin, A, Shilkina, Np, Yakusevich, Vv, Margoczy, R, Zubek, V, Dzupina, A, Dubrava, J, Dulkova, K, Fabryova, L, Gaspar, L, Kamensky, G, Kokles, M, Raslova, K, Soosova, I, Stevlik, J, Strbova, J, Sumbal, J, Uhliar, R, Micik, J, Truban, J, Fedacko, J, Pastrnakova, E, Pella, D, Fazekas, F, Ambrovicova, V, Kycina, P, Martinka, E, Nociar, J, Belicova, M, Banik, M, Kanderkova, D, Hranai, M, Duris, T, Krahulec, B, Benacka, J, Vinanska, D, Roskova, E, Skripova, D, Macek, V, Vohnout, B, Buganova, I, Engelbrecht, Jm, Pretorius, Mm, Ebrahim, Io, Bayat, J, Ganesh, S, Ranjith, N, Coetzer, Tf, Jacovides, A, Distiller, La, Hellig, Fs, Engelbrecht, Iv, Mahomed, Aa, Blignault, Sc, Burgess, Lj, Kotze, Hj, van Nieuwenhuizen, E, Musungaie, Db, Emanuel, S, van der Walt, E, Pretorius, Ce, Roos, Js, Roux, Sm, Badat, Ae, Fouche, L, Vahed, Ya, Jansen van Resburg, D, van Zyl LJ, Soto Gonzalez, A, Diaz, Jl, Segura, T, Botella Serrano, M, Botas Rodrigues, J, Molto-Jorda, Jm, Dominguez Escribano JR, Sogorb Garri, F, Blanco Coronado JL, Gaztambide Saenz MS, Brotons Cuixart, C, Bruguera Cortada, J, Garcia-Moll Marimon, X, Gonzalbez Morgaez JD, Maisterra Santos, O, Roquer Gonzalez, J, Sobrino-Martinez, J, Chueca Fernandez JE, Narejos, S, Suarez Garcia, S, Perez Martinez, P, Figueras Camos, R, Medrano Martinez, V, Bellido Guerrero, D, Martinez Deben, F, Vila Belmonte, A, Mediavilla Garcia JD, Romero Hinojosa JA, Martorell Mateu, E, Cequier Fillat AR, Pinto Sala, X, Adroer Martori, R, Bueno Diez, M, Lopez Cano, C, Worner Diz, F, Gonzalez Juanatey, C, Alvarez-Sala Walther LA, De Dios Garcia Diaz, J, Garcia Puig, J, Jodar Gimeno, E, Plaza Perez, I, Suarez-Fernandez, C, Tunon, J, Zamorano Gomez JL, Brito Sanfiel MA, Escudier Villa JM, de Mora Martin, M, Dominguez Lopez, M, Hernandez Garcia JM, Tinahones Madueno FJ, Perez Paredes, M, Aracil Villar, J, Barreda Gonzalez MJ, Ripoll Vera TV, Tofe Povedano, S, Sanchez Alvarez, J, Martinez Via, L, Robles Iniesta, A, Masana, L, Vinyoles Bargallo, E, Calvo Gomez, C, Gonzalez Juanatey JR, Cruz Fernandez JM, De La Cuesta Mayor, C, Duran Garcia, S, Jimenez Hernandez MD, Morales Portillo, C, Muniz Grijalvo, O, De Castro, R, Taverna Llaurado, E, Pons Amate JM, Terns Riera, M, Civeira Murillo, F, Linderfalk, C, Curiac, D, Saldeen-Nilehn, K, Koskinen, P, Khalili, P, Tortensson, I, Lindholm, Cj, Luts, A, Koskinen, Pt, Gottsater, A, Persson, Be, Mooe, T, Larnefeldt, H, Boman, K, Crisby, M, Rasmanis, G, Tengmark, Bo, Witt, N, Hagstrom, E, Viklund, J, Muller, C, Mach, F, Burnier, M, Nanchen, D, Wuerzner, G, Banyai, M, Moccetti, T, Miserez, Ar, Bilz, S, Weber, K, Lai, Wt, Chang, Kc, Ueng, Kc, Tsai, Wc, Chiang, Ce, Hou, C, Pei, D, Krittayaphong, R, Kiatchoosakun, S, Srimahachota, S, Boonyavarakul, A, Jintapakorn, W, Gullu, H, Onrat, E, Erkan, Af, Demirci, D, Sari, R, Ceyhan, C, Ari, H, Araz, M, Degertekin, M, Goktekin, O, Uresin, Ay, Yigit, Z, Akdeniz, B, Comlekci, A, Kayikcioglu, M, Sahin, T, Ozcan, T, Durakoglugil, E, Asamoah-Owusu, N, Reed, R, Bakhai, A, Dixon, L, Sharma, R, Avornyo, Aa, Jones, Af, Lip, G, Clark, R, Banerjee, M, Wakeling, J, Arden, C, Blagden, Md, Walukiewica, P, Marshall, A, Maxwell, Tg, Gunstone, Ae, Kadr, Hh, Patle, R, Arif, I, Jhund, Ps, Mckaig, G, Douglas, F, Mierzejewski, L, Turner, W, Sathyapalan, T, Ivan, P, Manoj, A, Rice, S, Collier, Dj, Nair, Dr, Thom, S, Fiore, G, De Belder, M, Price, D, Sobolewska, J, Martin, S, Takhar, A, Moriarty, A, Kondagunta, V, Myhill, T, Gibson, Jm, Cecil, Jt, Halcox, J, Annamalai, N, Gorog, Da, Mccormack, T, Pegge, N, Field, A, Adams, F, Klein, Jj, Busch, Rs, Bretton, Em, Jaffrani, N, Salacata, A, Assadourian, A, Gogia, Hs, Dyke, Ck, Rubenfire, M, Essandoh, Lk, Welker, Ja, Ledesma, G, Lupovitch, S, Delgado, Jp, Hendrix, El, Quyyumi, Aa, Riesenberg, Ra, Robertson, Dg, Weinstein, Dl, Weiss, R, Casaubon, L, Gammon, Rs, Brar, Hs, Bittar, Gd, Guarnieri, Tt, Ince CS Jr, Jrquraishi, Am, Saeed, S, Albert, M, Sotolongo, Rp, Bernard, Jv, Karlsbergg, Rp, Lepor, Ne, Kirby, We, Mclean, B, Miller, Ap, Ovalle, F, Townsend, Jc, Beckett, Pl, Eaves, Wb, West, Sh, Kosinski, Ej, Zarich, Sw, Mahal, Ss, Maw, K, Maynard, Km, Chen, Jc, Gelormini, J, Gottlieb, Dw, Gabra, Nw, Narayan, P, Sparks, J, Field, Jc, Willits, Vl, O’Steen, Mb, Pasquini, Ja, Sensebrenner, Jw, Yarows, Sa, Hiotis, L, Jagielo, Tj, Levinson, Dj, Diller, Pm, Kereiakes, Dj, Turner, Ta, Vincent, S, Camp, Ad, Denker, Ps, Manning, Mb, Rocco, Mb, Stamps, Hb, Strader, Jr, Uusinarkaus, Kt, Kennett, Jd, Leichter, Sb, Mcneil, Dl, Schumacher, Dr, Chang, Ar, Ellison, Hs, Updegrove, Jd, Hamroff, Gs, Kay, Js, Marar, Ie, Flores, E, Saini, S, Abdullah, S, Berk, Mr, Fordan, S, Joshi, Ph, Mccullough, Pa, Reynolds, Rd, Rosenstock, J, Sachson, Ra, Shammas, N, Fishbein, Gj, Randall, Wj, Henderson, Da, Nash, Ml, Barker, Ba, Cohen, Ss, Seidman, B, Odekirk, Ll, Grillo, Rs, Martinez, Lm, Multani, P, Alwine, Lk, Mcgarvey, Jf, Mollerus, Me, Miller, Ab, Kotek, Lw, Changlani, M, Zavaro, Sh, Munoz, F, Mehta, Pm, Helm, Rj, Farhat, Nz, Farsad, R, Raoof, Tj, Shultz, Jh, Geohas, Jg, Allaw, Ma, Dela Llana, A, Gutmann, Je, Inzerello, At, Alappat, P, George, Ar, Haddad, Tm, Lillestol, Mj, Grodman, R, Peniston, Jh, Wadud, K, Garcia, B, Hamilton, Me, Lerman, S, Perloff, De, Graff, A, Saxena, S, Alvarado, Op, Malik, A, Reddy, Rd, Kinzfogl, G, Cornett, Gm, Norwood, Pc, Gilbert, Jm, Willis, Jg, Mcgrew, F, Sharma, S, Castro, Ma, Cucher, Fh, Altafullah, Im, Khurana, S, Knutson, Tj, Kinnaman, Sj, Stuckey, T, Pudi, Kk, Mayfield, Rk, Funk, Gs, Nixon, Wa, Dor, I, Boyett, Be, Srivastava, S, Elosegui, Am, Isserman, Sm, Cheek, Hb, Promisloff, Sd, Tami, Lf, Zeig, S, fitz-Patrick, D, Dave, Kn, Ahmad, A, Arain, S, Ballantyne, Cm, Doshi, A, El Hafi SE, Feldman, J, Fragoso, Vg, Gilford, T, Hoffman, As, Pouzar, Je, Vivekananthan, K, Ansari, Sh, Strzinek, Ra, Crater, Ta, Robinson, Jg, Fulmer, Jj, Patel, Am, Pereira, Es, Stich, Ma, Sultan, S, Geskin, G, Ruoff, Ge, Gillespie, E, Bybee, Ka, Moriarty, Pm, Savin, V, Agaiby, Jm, Melucci, Mb, Jantzi, Cm, Davidson, E, Smith, Wb, Treasure, Cb, Wakefield, Ph, Deck, K, Edris, Ma, Gilmore, Rm, Seep, Mk, Andersen, Jl, Detweiler, Ro, Rosenfeld, Jc, Strobl, Dj, Steinhoff, Jp, Adams, A, Estevez, R, Molin, Cj, Kim, Cy, Dy, J, Fox, Ke, Farris, Nr, Wayne, Jd, Whitney, Rt, Randhawa, Pm, Mego, Dm, Macdolnald, L, Caputo, Rp, Rigolosi, R, Vannatta, B, Pacheco, Tr, El-Shahawy, M, Gonzalez, Ej, Guice, Mj, Cherlin, Rs, Bays, He, Shoukfeh, M, Morris, Fh, Loy, J, Vora, Sk, Staab, Pk, Frisoli, A, Kimmel, Ma, Cohen, Aj, Green, Cb, Whitlock, L, Butuk, Dj, Mccartney, Mj, Ables, Lr, Acosta, R, Alvarez, Jg, Barrera, Cm, Benitez, O, Berenguer, Ra, Breton, Cf, Chiong, R, Delgado, Mi, Dufreny, A, Fialkow, Ja, Franczek, S, Frias, Jj, Iglesias, C, Landron-Garcia, L, Llerena, Sn, Martinez, Rf, Miranda, Aa, Morytko, Ja, Rodriguez, Ij, Sotolongo, R, Suarez-Sarmiento, A, Terrelonge, Ae, Vaca, Ce, Venereo, Jm, Verdeza, C, Zeno, Ml, Chilka, S, Felten, Wr, Hartman, An, Shayani, Ss, Duprez, D, Knickelbine, T, Chambers, Jd, Cone, Cl, Broughton, R, Napoli, Mc, Seaton, Bl, Smith, Sk, Reedy, Ma, Kesani, Mk, Nicol, Pr, Stringam, So, Talano, Jv, Barnum, O, Desai, V, Montero, M, Jacks, Rk, Kostis, Jb, Owen, Jg, Makam, Sk, Grosman, I, Underberg, Ja, Masri, Be, Peters, Ss, Serje, J, Lenhard, Mj, Glover, R, Paraboschi, Cf, Lim, Eh, Connery, L, Kipgen, W, Bravo, P, Digiovanna, Mj, Tayoum, H, Gabriel, Jd, Ariani, Mk, Robinson, Mf, Clemens, Pc, Corder, Cn, Schifferdecker, B, Tahirkheli, Nk, Hurling, Rt, Rendell, Ms, Shivaswamy, V, Madu, Ij, Dahl, Cf, Ayesu, K, Kim, C, Barettella, Mb, Jamidar, Ha, Bloom, Sa, Vora, Kn, Ong, St, Aggarwala, G, Sack, G, Blaze, K, Krichmar, P, Murcia, A, Teltser, M, Villaman-Bencosme, Y, Fahdi, Ie, Williams, Dg, Lain, El, Garcia, Hl, Karim, Sn, Francyk, Dm, Gordon, Mb, Palchick, Ba, Mckenzie, Me, Gimness, Mp, Greiff, J, Ruiz-R, L, Vazquez-Tanus, Jb, Schlager, D, Connelly, T, Soroka, E, Hastings, Wl, O’Dea, Dj, Purdy, Da, Jackson, B, Arcanese, Ml, Strain, Je, Schmedtje JF Jr, Jrdavis, Mg, A, A, Prasada, S, Scott, Dl, Vukotic, G, Akhtar, N, Larsen, Dc, Rhudy, Jm, Zebrack, Js, Bailey, Sr, Grant, Dc, Mora, A, Perez, Ja, Reyes, Rg, Sutton, Jc, Brandon, Dm, First, Bp, Risser, Ja, Claudio, J, Figueroa-Cruz, Wl, Sosa-Padilla, Ma, Tan, Ae, Traboulssi, Ma, Morcos, Nc, Glaser, La, Bredlau, Ce, El Shahawy, M, Ramos, Mj, Kandath, Dd, Kaluski, E, Akright, L, Rictor, Kw, Pluto, Tm, Hermany, Pr, Bellingar, B, Clark, Gb, Herrod, Jn, Goisse, M, Hook, M, Barrington, P, Lentz, Jd, Singal, Dk, Gleason, Gp, Lipetz, Rs, Schuchard, Tn, Bonner, Jh, Forgosh, Lb, Lefebvre, Gc, Pierpoint, Be, Radin, Dm, Stoller, Sr, Segall, N, Shah, Sa, Ramstad, Ds, Nisnisan, Jm, Trippett, Jm, Benjamin, Sa, Labissiere, Jc, Nashed, An, Maaieh, M, Aslam, Aa, Mandviwala, M, Budoff, Mj, French, Wj, Vlach, Jj, Destefano, P, Bayron, Cj, Fraser, Nj, Sandberg, Jh, Fagan, Tc, Peart, Bc, Suryanarayana, Pg, Gupta, Dk, Lee, Mw, Bertolet, Bd, Hartley, Pa, Kelberman, M, Behmanesh, B, Buynak, Rj, Chochinov, Rh, Steinberg, Aa, Chandna, H, Bjasker, Kr, Perlman, Rl, Ball, Em, Pock, J, Singh, S, Baldari, D, Kaster, S, Lovell, Jp, Horowitz, Bs, Gorman, Ta, Pham, Dn, Landzberg, Js, Mootoo, Ki, Moon, E, Krawczyk, J, Alfieri, Ad, Janik, Mj, Herrington, Dm, Koilpillai, Rn, Waxler, Ar, Hoffman, Da, Sahul, Zh, Gumbiner, B, Cropp, A, Fujita, K, Garzone, P, Imai, K, Levisetti, M, Plowchalk, D, Sasson, S, Skaggs, J, Sweeney, K, Vincent, J., Curto, M, Ridker, P., Revkin, J., Amarenco, P., Brunell, R., Curto, M., Civeira, F., Flather, M., Glynn, R., Gregoire, J., Jukema, J., Karpov, Y., Kastelein, J., Koenig, W., Lorenzatti, A., Manga, P., Masiukiewicz, U., Miller, M., Mosterd, A., Murin, J., Nicolau, J., Nissen, S., Ponikowski, P., Santos, R., Schwartz, P., Soran, H., White, H., Wright, R., Vrablik, M., Yunis, C., Shear, C., Tardif, J., SPIRE Cardiovascular Outcome Investigators, Averna, M., Brigham and Women's Hospital [Boston], Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), RS: CARIM - R3.02 - Hypertension and target organ damage, MUMC+: MA Alg Interne Geneeskunde (9), Interne Geneeskunde, Ridker, P. M., Glynn, R. J., Jukema, J. W., Kastelein, J. J. P., Nicolau, J. C., Santos, R. D., Schwartz, P. F., Wright, R. S., Shear, C. L., Tardif, J. -C., SPIRE Cardiovascular Outcome Investigator, Perrone, Filardi, P, Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes
Subjects: Male, STATIN THERAPY, Anticholesteremic Agents/adverse effects, Antibodie, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Injections, Subcutaneous/adverse effects, 030204 cardiovascular system & hematology, Bococizumab, law.invention, PCSK9, 0302 clinical medicine, Randomized controlled trial, law, Risk Factors, GENETIC-VARIANTS, Cardiovascular Disease, Monoclonal, Anticholesteremic Agent, 030212 general & internal medicine, Myocardial infarction, Treatment Failure, Humanized, Proprotein Convertase 9/antagonists & inhibitors, Medicine(all), Antibodies, Antibodies, Monoclonal, Humanized, Anticholesteremic Agents, Cardiovascular Diseases, Cholesterol, LDL, Double-Blind Method, Female, Follow-Up Studies, Humans, Hypercholesterolemia, Injections, Subcutaneous, Lipids, Middle Aged, Proprotein Convertase 9, Medicine (all), PCSK9 Inhibitors, antibodies monoclonal humanized, anticholesteremic agents, cardiovascular diseases, cholesterol, LDL, double-blind method, female, follow-up studies, humans, hypercholesterolemia, injections, subcutaneous, lipids, male, middle aged, proprotein convertase 9, risk factors, treatment failure, medicine (all), Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], General Medicine, Lipid, 3. Good health, LDL/blood, Multicenter Study, Cholesterol, TRIALS, Cholesterol, LDL/blood, Antibodies, Monoclonal, Humanized/adverse effects, Randomized Controlled Trial, subcutaneous, lipids (amino acids, peptides, and proteins), Cardiovascular Diseases/prevention & control, REDUCING LIPIDS, Human, medicine.medical_specialty, animal structures, Hypercholesterolemia/drug therapy, Placebo, Injections, Subcutaneou, LDL, Injections, Follow-Up Studie, EVENTS, 03 medical and health sciences, Internal medicine, medicine, Journal Article, Comparative Study, METAANALYSIS, Alirocumab, business.industry, Unstable angina, Lipids/blood, Risk Factor, fungi, Antibodies/blood, ta3121, medicine.disease, Surgery, Evolocumab, REDUCTION, Humanized/adverse effects, Subcutaneous/adverse effects, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Item does not contain fulltext BACKGROUND: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS: At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P/=70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of >/=100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P
Published: 2017

11. Implementation Strategies to Improve Non-HDL-Cholesterol Goal Attainment.

Author: Virani, Salim S.
Subjects: *CARDIOVASCULAR diseases risk factors, *CHOLESTEROL, *HIGH density lipoproteins, *LOW density lipoproteins, *BLOOD lipoproteins
Abstract: The article discusses the strategies for improving non-high-density-lipoprotein cholesterol (non-HDL-C) goal attainment. It was suggested that non-HDL-C is a better cardiovascular risk marker compared with low-density-lipoprotein cholesterol (LDL-C). The reasons for lower non-HDL-C goal attainment are cited. A conceptual model of how to improve non-HDL-C goal attainment is also discussed.
Published: 2012

12. Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III study

Author: Pivonello, Rosario, Petersenn, Stephan, Newell-Price, John, Findling, James, Gu, Feng, Maldonado, Mario, Trovato, Andrew, Hughes, Gareth, Salgado, Luiz, Lacroix, André, Schopohl, Jochen, Biller, Beverly, Pasireotide B2305 Study Group, ., Department of Molecular and Clinical Endocrinology and Oncology, Università degli studi di Napoli Federico II, University of Sheffield [Sheffield], Sheffield Teaching Hospitals National Health Service Foundation Trust, Novartis Institute for Tropical Diseases (NITD), Clinical Pharmacology, Novartis Pharmaceutical Corporation, Division of General Internal Medicine, Hospital das Clinicas-University of Sao Paulo Medical School, Centre d'études biologiques de Chizé (CEBC), Centre National de la Recherche Scientifique (CNRS), Medizinische Klinik IV, University of Munich, Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pivonello, R, Petersenn, S, Newell-Price, J, Findling, J, Gu, F, Maldonado, M, Trovato, A, Hughes, G, Salgado, L, Lacroix, A, Schopohl, J, and Biller, B.
Subjects: Male, Somatostatin/therapeutic use, medicine.medical_specialty, Waist, Randomization, Lipoproteins, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Medizin, Disease, Cholesterol/blood, chemistry.chemical_compound, Endocrinology, Double-Blind Method, Internal medicine, medicine, Humans, In patient, Cushing Syndrome/drug therapy, Adverse effect, Cushing Syndrome, Waist Circumference/physiology, business.industry, Cushing's disease, medicine.disease, Pasireotide, LDL/blood, 3. Good health, Lipoproteins, LDL, Cholesterol, Blood pressure, chemistry, Female, Waist Circumference, Somatostatin, business
Abstract: International audience; ObjectiveSigns and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with Cushing's disease.DesignPhase III study with double-blind randomization of two pasireotide doses.MethodsPatients (n=162) with persistent/recurrent or de novo Cushing's disease and urinary free cortisol (UFC) levels ≥1·5× upper limit of normal (ULN) were randomized to receive subcutaneous pasireotide (600/900μg bid). At month 3, patients with UFC≤2×ULN and not exceeding the baseline value continued their randomized dose; all others received 300μg bid uptitration. At month 6, patients could enter an open-label phase until month 12 with a maximal dose of 1200μg bid. Changes in signs and symptoms of hypercortisolism over 12months' treatment in patients still enroled in the study and with evaluable measurements were assessed in relation to degree of UFC control.ResultsReductions in blood pressure were observed even without full UFC control and were greatest in patients who did not receive antihypertensive medications during the study. Significant reductions in total cholesterol and low-density lipoprotein (LDL)-cholesterol were observed in patients who achieved UFC control. Reductions in BMI, weight and waist circumference occurred during the study even without full UFC control. Adverse effects were typical of somatostatin analogues except for hyperglycaemia-related events, which were experienced by 72·8% of patients.ConclusionsIn the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12months of pasireotide treatment, as UFC levels decreased.
Published: 2014

13. Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study

Subjects: Hyperlipidemias/drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Clinical Neurology, Mendelian Randomization Analysis, Research Support, Stroke/epidemiology, LDL/blood, Causality, Cholesterol, Hypolipidemic Agents/therapeutic use, Journal Article, Humans, Brain Ischemia/epidemiology, Non-U.S. Gov't, Coronary Disease/epidemiology
Abstract: To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach.MethodsWe undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity.ResultsA 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 × 10 -8). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 × 10 -3) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 × 10 -3) when compared with that for CHD.ConclusionsIn contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
Published: 2019

14. Common variants associated with plasma triglycerides and risk for coronary artery disease

Author: Richard S. Cooper, Angela Döring, Cisca Wijmenga, Jerome I. Rotter, Linda S. Adair, Tõnu Esko, Jennifer L. Bragg-Gresham, Danish Saleheen, Narisu Narisu, Xiaohui Li, Kathleen Stirrups, Ulf de Faire, Nicholas G. Martin, Dmitry Shungin, Peter Vollenweider, Yii-Der Ida Chen, Dharambir K. Sanghera, George Dedoussis, Toshiko Tanaka, Manjinder S. Sandhu, Anne U. Jackson, Nancy L. Pedersen, Maria Dimitriou, Shih-Yi Lin, David P. Strachan, Isleifur Olafsson, Ruth J. F. Loos, Kay-Tee Khaw, Antero Kesäniemi, Rainer Rauramaa, Wendy L. McArdle, Gonneke Willemsen, Dena G. Hernandez, May E. Montasser, Amy J. Swift, Colin A. McKenzie, Aaron Isaacs, Latonya F. Been, Leif Groop, Massimo Mangino, Martina Müller-Nurasyid, Karen L. Mohlke, Ci Song, Sailaja Vedantam, Anna-Liisa Hartikainen, Lori L. Bonnycastle, Ilja M. Nolte, Jaakko Kaprio, Anneli Pouta, Unnur Thorsteinsdottir, Paul Elliott, Muredach P. Reilly, Jean Ferrières, Daniel J. Rader, Elizabeth H. Young, Jaspal S. Kooner, Leena Moilanen, Markku Laakso, Albert Hofman, Kelly A. Volcik, Sekar Kathiresan, Tamara B. Harris, Eric Kim, Aimo Ruokonen, Andrea Ganna, Serena Sanna, John J.P. Kastelein, Martha L. Gravito, Ronald M. Krauss, Ken K. Ong, Paul M. Ridker, Kristian Hveem, Ayse Demirkan, Alena Stančáková, Pierre Meneton, Thomas Quertermous, John Danesh, Toby Johnson, Cornelia M. van Duijn, Samuli Ripatti, Christopher J. Groves, Jaakko Tuomilehto, Michael Boehnke, Jose M. Ordovas, Alan B. Feranil, Chao A. Hsiung, Wayne Huey-Herng Sheu, Igor Rudan, Christa Meisinger, Rebecca N. Nsubuga, Bruna Gigante, Inger Njølstad, Göran Hallmans, Aroon D. Hingorani, Jouko Saramies, Deepti Gurdasani, Fernando Rivadeneira, Andres Metspalu, Stephen E. Epstein, Gonçalo R. Abecasis, Braxton D. Mitchell, Devin Absher, Marcus E. Kleber, Sonia Shah, Pierre Fontanillas, Jeffrey R. O'Connell, Louise A. Donnelly, Jing Hua Zhao, Martin L. Buchkovich, Francis S. Collins, Gabrielle Müller, Matti Uusitupa, Evelin Mihailov, Nicholas J. Wareham, Andrew A. Hicks, Dorret I. Boomsma, Harry Campbell, Ellen M. Schmidt, Jaana Lindström, Mark I. McCarthy, Evita G. Van Den Herik, Kirsten Ohm Kyvik, Vilmundur Gudnason, Jackie F. Price, Joel N. Hirschhorn, Winfried März, Aravinda Chakravarti, Pontiano Kaleebu, James F. Wilson, Lindsay L. Waite, Leo-Pekka Lyytikäinen, Sebanti Sengupta, Mika Kivimäki, David Altshuler, Hilma Holm, Rona J. Strawbridge, Harald Grallert, Ramaiah Nagaraja, Laurence Tiret, G. Kees Hovingh, Meena Kumari, Nilesh J. Samani, Daniel F. Freitag, Nelson B. Freimer, Thomas Illig, Panos Deloukas, Bernhard O. Boehm, Nicholas W.J. Wainwright, Mark J. Daly, Mika Kähönen, Michel Burnier, Norman Klopp, L. Adrienne Cupples, Aarno Palotie, Markus Perola, Bamidele O. Tayo, Timo A. Lakka, Matthew Jones, Sarah H. Wild, Patricia B. Munroe, Antti Jula, François Mach, Peter J. Koudstaal, Pirjo Komulainen, Eric Boerwinkle, L. Joost van Pelt, Veikko Salomaa, Ann-Kristin Petersen, Ida Surakka, Andrew Wong, Caroline Hayward, Chi Gao, Cristen J. Willer, Stephen S. Rich, Yi Jen Hung, Peter P. Pramstaller, Diana Kuh, Ron Do, Dominique Arveiler, Mark O. Goodarzi, Ross M. Fraser, Ingrid B. Borecki, Steven C. Hunt, Weihua Zhang, Mary Susan Burnett, Patrik K. E. Magnusson, John C. Chambers, Benjamin M. Neale, Peter Schwarz, Jennifer L. Bolton, Murielle Bochud, Heleen M. den Hertog, Christian Gieger, Cristina Pomilla, Teresa Ferreira, Lars Wallentin, Richa Saxena, André G. Uitterlinden, Kaisa Silander, Ying Wu, Bruce M. Psaty, Jian'an Luan, Hsing-Yi Chang, Jin Chen, Daniel I. Chasman, Ulf Gyllensten, Kari Stefansson, Kauko Heikkilä, Tom Wilsgaard, Alan R. Shuldiner, Carlos Iribarren, Stavroula Kanoni, John Whitfield, Gershim Asiki, Marika Kaakinen, Georg Ehret, Elina Hyppönen, Claudia Langenberg, Gina M. Peloso, Cecilia M. Lindgren, Carlo Sidore, Gudmundur I. Eyjolfsson, Cameron D. Palmer, Jacques S. Beckmann, Hubert Scharnagl, Tanya M. Teslovich, Mary F. Feitosa, Terho Lehtimäki, Steve E. Humphries, Chris Power, Benjamin F. Voight, Stefania Bandinelli, Andrew D. Morris, Gudmar Thorleifsson, Tuomo Nieminen, Tim D. Spector, Paul W. Franks, Themistocles L. Assimes, Pascal Bovet, Luigi Ferrucci, Johannes Kettunen, Inês Barroso, Franklyn I. Bennett, Stefan Gustafsson, Paolo Brambilla, Theodore Papamarkou, Elena Tremoli, Janet Seeley, Alex S. F. Doney, Johanna Kuusisto, Giancarlo Cesana, Bruce H. R. Wolffenbuttel, Lars Lind, Stefan R. Bornstein, Åsa Johansson, Anders Hamsten, Marjo-Riitta Järvelin, Krista Fischer, Agneta Siegbahn, Samia Mora, Erik Ingelsson, Colin N. A. Palmer, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Epidemiology, Surgery, Public Health, Ophthalmology, Neurology, Medical Microbiology & Infectious Diseases, Obstetrics & Gynecology, Internal Medicine, Do, Ron, Willer, Cristen J, Schmidt, Ellen M, Sengupta, Sebanti, Hyppönen, Elina, Kathiresan, Sekar, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Do, R, Willer, C, Schmidt, E, Sengupta, S, Gao, C, Peloso, G, Gustafsson, S, Kanoni, S, Ganna, A, Chen, J, Buchkovich, M, Mora, S, Beckmann, J, Bragg Gresham, J, Chang, H, Demirkan, A, Den Hertog, H, Donnelly, L, Ehret, G, Esko, T, Feitosa, M, Ferreira, T, Fischer, K, Fontanillas, P, Fraser, R, Freitag, D, Gurdasani, D, Heikkilä, K, Hyppönen, E, Isaacs, A, Jackson, A, Johansson, A, Johnson, T, Kaakinen, M, Kettunen, J, Kleber, M, Li, X, Luan, J, Lyytikäinen, L, Magnusson, P, Mangino, M, Mihailov, E, Montasser, M, Müller Nurasyid, M, Nolte, I, O'Connell, J, Palmer, C, Perola, M, Petersen, A, Sanna, S, Saxena, R, Service, S, Shah, S, Shungin, D, Sidore, C, Song, C, Strawbridge, R, Surakka, I, Tanaka, T, Teslovich, T, Thorleifsson, G, Van den Herik, E, Voight, B, Volcik, K, Waite, L, Wong, A, Wu, Y, Zhang, W, Absher, D, Asiki, G, Barroso, I, Been, L, Bolton, J, Bonnycastle, L, Brambilla, P, Burnett, M, Cesana, G, Dimitriou, M, Doney, A, Döring, A, Elliott, P, Epstein, S, Eyjolfsson, G, Gigante, B, Goodarzi, M, Grallert, H, Gravito, M, Groves, C, Hallmans, G, Hartikainen, A, Hayward, C, Hernandez, D, Hicks, A, Holm, H, Hung, Y, Illig, T, Jones, M, Kaleebu, P, Kastelein, J, Khaw, K, Kim, E, Klopp, N, Komulainen, P, Kumari, M, Langenberg, C, Lehtimäki, T, Lin, S, Lindström, J, Loos, R, Mach, F, Mcardle, W, Meisinger, C, Mitchell, B, Müller, G, Nagaraja, R, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Ong, K, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Rader, D, Reilly, M, Ridker, P, Rivadeneira, F, Rudan, I, Ruokonen, A, Samani, N, Scharnagl, H, Seeley, J, Silander, K, Stančáková, A, Stirrups, K, Swift, A, Tiret, L, Uitterlinden, A, van Pelt, L, Vedantam, S, Wainwright, N, Wijmenga, C, Wild, S, Willemsen, G, Wilsgaard, T, Wilson, J, Young, E, Zhao, J, Adair, L, Arveiler, D, Assimes, T, Bandinelli, S, Bennett, F, Bochud, M, Boehm, B, Boomsma, D, Borecki, I, Bornstein, S, Bovet, P, Burnier, M, Campbell, H, Chakravarti, A, Chambers, J, Chen, Y, Collins, F, Cooper, R, Danesh, J, Dedoussis, G, de Faire, U, Feranil, A, Ferrières, J, Ferrucci, L, Freimer, N, Gieger, C, Groop, L, Gudnason, V, Gyllensten, U, Hamsten, A, Harris, T, Hingorani, A, Hirschhorn, J, Hofman, A, Hovingh, G, Hsiung, C, Humphries, S, Hunt, S, Hveem, K, Iribarren, C, Järvelin, M, Jula, A, Kähönen, M, Kaprio, J, Kesäniemi, A, Kivimaki, M, Kooner, J, Koudstaal, P, Krauss, R, Kuh, D, Kuusisto, J, Kyvik, K, Laakso, M, Lakka, T, Lind, L, Lindgren, C, Martin, N, März, W, Mccarthy, M, Mckenzie, C, Meneton, P, Metspalu, A, Moilanen, L, Morris, A, Munroe, P, Njølstad, I, Pedersen, N, Power, C, Pramstaller, P, Price, J, Psaty, B, Quertermous, T, Rauramaa, R, Saleheen, D, Salomaa, V, Sanghera, D, Saramies, J, Schwarz, P, Sheu, W, Shuldiner, A, Siegbahn, A, Spector, T, Stefansson, K, Strachan, D, Tayo, B, Tremoli, E, Tuomilehto, J, Uusitupa, M, van Duijn, C, Vollenweider, P, Wallentin, L, Wareham, N, Whitfield, J, Wolffenbuttel, B, Altshuler, D, Ordovas, J, Boerwinkle, E, Thorsteinsdottir, U, Chasman, D, Rotter, J, Franks, P, Ripatti, S, Cupples, L, Sandhu, M, Rich, S, Boehnke, M, Deloukas, P, Mohlke, K, Ingelsson, E, Abecasis, G, Daly, M, Neale, B, and Kathiresan, S
Subjects: Netherlands Twin Register (NTR), BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Heart disease, Genome-wide association study, Coronary Artery Disease, 030204 cardiovascular system & hematology, ISCHEMIC-HEART-DISEASE, Triglyceride, Coronary artery disease, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Polymorphism (computer science), Risk Factors, High-density-lipoprotein, Genetic epidemiology, 11 Medical and Health Sciences, Genetics & Heredity, 0303 health sciences, Cholesterol, HDL/blood, Cholesterol levels, Loci, Contribute, Single Nucleotide, LDL/blood, Triglycerides/blood, Cholesterol, Cholesterol, LDL/blood, HDL/blood, lipids (amino acids, peptides, and proteins), Life Sciences & Biomedicine, Human, medicine.medical_specialty, TYPE-2 DIABETES-MELLITUS, Biology, Polymorphism, Single Nucleotide, Article, HIGH-DENSITY-LIPOPROTEIN ISCHEMIC-HEART-DISEASE TYPE-2 DIABETES-MELLITUS MENDELIAN RANDOMIZATION CARDIOVASCULAR-DISEASE GENETIC EPIDEMIOLOGY CHOLESTEROL LEVELS LOCI CONTRIBUTE THERAPY, 03 medical and health sciences, Coronary Artery Disease/blood, SDG 3 - Good Health and Well-being, Cardiovascular-disease, Internal medicine, Mendelian randomization, Genetics, medicine, Humans, Polymorphism, plasma, Triglycerides, 030304 developmental biology, Science & Technology, Risk Factor, Cholesterol, HDL, Biological Transport, Cholesterol, LDL, 06 Biological Sciences, medicine.disease, Heart-disease, lipoproteins, Endocrinology, chemistry, Therapy, Developmental Biology
Abstract: Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10 -8 for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. © 2013 Nature America, Inc. All rights reserved.
Published: 2013

15. Risk Scores of Common Genetic Variants for Lipid Levels Influence Atherosclerosis and Incident Coronary Heart Disease

Author: Jacqueline C.M. Witteman, Ben A. Oostra, André G. Uitterlinden, Sara M. Willems, Albert Hofman, Cornelia M. van Duijn, Oscar H. Franco, Aaron Isaacs, Abbas Dehghan, M. Arfan Ikram, Daniel Bos, Epidemiology, Radiology & Nuclear Medicine, Internal Medicine, and Clinical Genetics
Subjects: Male, Myocardial Infarction/genetics, Disease, 030204 cardiovascular system & hematology, Carotid Intima-Media Thickness, Rotterdam Study, 0302 clinical medicine, Gene Frequency, Carotid Artery Diseases/blood, Risk Factors, Myocardial infarction, Cholesterol, HDL/blood, 0303 health sciences, Framingham Risk Score, Incidence, Incidence (epidemiology), Single Nucleotide, Middle Aged, Prognosis, LDL/blood, 3. Good health, Triglycerides/blood, Cholesterol, Phenotype, Cholesterol, LDL/blood, HDL/blood, Cardiology, Female, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, Risk assessment, Adult, medicine.medical_specialty, Netherlands/epidemiology, Cholesterol/blood, Polymorphism, Single Nucleotide, Risk Assessment, 03 medical and health sciences, Coronary Disease/blood, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Genetic variability, Polymorphism, Aged, Proportional Hazards Models, 030304 developmental biology, Lipids/blood, Proportional hazards model, business.industry, medicine.disease, Asymptomatic Diseases, Linear Models, business, Biomarkers/blood
Abstract: Objective— Circulating levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides are recognized risk factors for cardiovascular disease. We tested the hypothesis that the cumulative effects of common genetic variants for lipids are collectively associated with subclinical atherosclerosis and incident coronary heart disease. Approach and Results— Participants were drawn from the Erasmus Rucphen Family Study (n=2269) and the Rotterdam Study (n=8130). Linear regression and Cox proportional hazards models were applied to assess the influence of 4 risk scores derived from common genetic variants for lipids (total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglycerides) on carotid plaque, intima-media thickness, incident myocardial infarction, and coronary heart disease. Adjusted for age and sex, all 4 risk scores were associated with carotid plaque. This relationship was the strongest for the LDL-C score, which increased plaque score by 0.102 per SD increase in genetic risk score ( P =3.2×10 −8 ). The LDL-C score was also nominally associated with intima-media thickness, which increased 0.006 mm per SD increase in score ( P =0.05). Both the total cholesterol and LDL-C scores were associated with incident myocardial infarction and coronary heart disease with hazard ratios between 1.10 and 1.13 per SD increase in score. Inclusion of additional risk factors as covariates minimally affected these results. Conclusions— Common genetic variants with small effects on lipid levels are, in combination, significantly associated with subclinical and clinical cardiovascular outcomes. As knowledge of genetic variation increases, preclinical genetic screening tools might enhance the prediction and prevention of clinical events.
Published: 2013
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16. Discovery and refinement of loci associated with lipid levels

Author: Benjamin F. Voight, Stefania Bandinelli, Pascal Bovet, Latonya F. Been, Ci Song, Luigi Ferrucci, Johannes Kettunen, Andrew D. Morris, Mary Susan Burnett, Ronald M. Krauss, Igor Rudan, Heleen M. den Hertog, Stavroula Kanoni, G. Kees Hovingh, Elina Hyppönen, Kauko Heikkilä, Richard S. Cooper, Daniel I. Chasman, Bruna Gigante, Stefan Gustafsson, Jian'an Luan, Sarah H. Wild, Patricia B. Munroe, Göran Hallmans, Jeffrey R. O'Connell, Danish Saleheen, Aarno Palotie, Leena Moilanen, Jerome I. Rotter, Caroline Hayward, Jennifer L. Bragg-Gresham, Nicholas G. Martin, Claudia Langenberg, George Dedoussis, Carlo Sidore, Ulf Gyllensten, Marika Kaakinen, Jing Hua Zhao, Aimo Ruokonen, Diana Kuh, Maria Dimitriou, Shih-Yi Lin, Gina M. Peloso, Marcus E. Kleber, Christopher J. Groves, Alena Stančáková, Michel Burnier, Patrik K. E. Magnusson, John C. Chambers, Giancarlo Cesana, Francis S. Collins, Gabrielle Müller, Angela Döring, Colin A. McKenzie, Paul Elliott, Lars Lind, Vilmundur Gudnason, Dharambir K. Sanghera, Jean Ferrières, Toshiko Tanaka, Stefan R. Bornstein, Gershim Asiki, Jacques S. Beckmann, Anneli Pouta, Timo A. Lakka, Daniel J. Rader, Elizabeth H. Young, Kelly A. Volcik, Dena G. Hernandez, Ann-Kristin Petersen, Kristian Hveem, Amy J. Swift, Murielle Bochud, Pierre Meneton, Paul M. Ridker, Kathleen Stirrups, Stephen S. Rich, Isleifur Olafsson, Ruth J. F. Loos, Serena Sanna, Markus Perola, Meena Kumari, Cameron D. Palmer, Carlos Iribarren, Nancy L. Pedersen, Mark O. Goodarzi, Panos Deloukas, Norman Klopp, Cristina Pomilla, Stephen E. Epstein, Antti Jula, Themistocles L. Assimes, Martina Müller-Nurasyid, Marjo-Riitta Järvelin, Chao A. Hsiung, Sonia Shah, Christian Gieger, Toby Johnson, Cornelia M. van Duijn, Samuli Ripatti, Nicholas J. Wareham, Krista Fischer, Wendy L. McArdle, Linda S. Adair, Kay-Tee Khaw, Bruce M. Psaty, André G. Uitterlinden, Aaron Isaacs, Tõnu Esko, Jennifer L. Bolton, Rebecca N. Nsubuga, Eric Boerwinkle, L. Joost van Pelt, Jouko Saramies, François Mach, Pierre Fontanillas, Teresa Ferreira, Lars Wallentin, Michael Boehnke, Christa Meisinger, Wayne Huey-Herng Sheu, Gonçalo R. Abecasis, Inês Barroso, Franklyn I. Bennett, Dmitry Shungin, Jaakko Kaprio, Kirsten Ohm Kyvik, Deepti Gurdasani, Anne U. Jackson, Paolo Brambilla, Georg Ehret, Cecilia M. Lindgren, Fernando Rivadeneira, Theodore Papamarkou, Jaakko Tuomilehto, Cristen J. Willer, Martin L. Buchkovich, Antero Kesäniemi, Hubert Scharnagl, Xiaohui Li, Elena Tremoli, Nelson B. Freimer, Mika Kähönen, Ron Do, Karen L. Mohlke, Thomas Illig, Gudmar Thorleifsson, Peter J. Koudstaal, Andres Metspalu, Ulf de Faire, Dominique Arveiler, Harald Grallert, Jaana Lindström, Laurence Tiret, Jaspal S. Kooner, Braxton D. Mitchell, Sebanti Sengupta, Gonneke Willemsen, Anna-Liisa Hartikainen, Terho Lehtimäki, Steve E. Humphries, Peter Schwarz, Dorret I. Boomsma, Harry Campbell, Ellen M. Schmidt, Tom Wilsgaard, Janet Seeley, Alex S. F. Doney, Alan R. Shuldiner, John Whitfield, Markku Laakso, Peter Vollenweider, Gudmundur I. Eyjolfsson, Winfried März, Mika Kivimäki, Ying Wu, Johanna Kuusisto, Andrew A. Hicks, Bruce H. R. Wolffenbuttel, May E. Montasser, Bamidele O. Tayo, Unnur Thorsteinsdottir, Muredach P. Reilly, Leo-Pekka Lyytikäinen, Eric Kim, John Danesh, Ida Surakka, Åsa Johansson, Anders Hamsten, Thomas Quertermous, Hsing-Yi Chang, Jin Chen, Agneta Siegbahn, Narisu Narisu, Samia Mora, Erik Ingelsson, Colin N. A. Palmer, Sekar Kathiresan, Manjinder S. Sandhu, Leif Groop, Jose M. Ordovas, Alan B. Feranil, Evelin Mihailov, Hilma Holm, Pontiano Kaleebu, Lindsay L. Waite, Ramaiah Nagaraja, Andrew Wong, Rona J. Strawbridge, David P. Strachan, Yii-Der Ida Chen, Tamara B. Harris, Jackie F. Price, Aravinda Chakravarti, Veikko Salomaa, Sailaja Vedantam, Albert Hofman, Devin Absher, Ross M. Fraser, Kaisa Silander, Pirjo Komulainen, Yi Jen Hung, Peter P. Pramstaller, Kari Stefansson, Aroon D. Hingorani, Tanya M. Teslovich, Matti Uusitupa, L. Adrienne Cupples, Cisca Wijmenga, Lori L. Bonnycastle, Ilja M. Nolte, Andrea Ganna, Ken K. Ong, Inger Njølstad, Bernhard O. Boehm, Nicholas W.J. Wainwright, Richa Saxena, Rainer Rauramaa, Louise A. Donnelly, James F. Wilson, Matthew Jones, Ingrid B. Borecki, Steven C. Hunt, Weihua Zhang, Massimo Mangino, John J.P. Kastelein, Martha L. Gravito, Mark I. McCarthy, Evita G. Van Den Herik, Joel N. Hirschhorn, Nilesh J. Samani, Daniel F. Freitag, Ayse Demirkan, Mary F. Feitosa, Tuomo Nieminen, Tim D. Spector, Paul W. Franks, Chris Power, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Willer, C, Schmidt, E, Sengupta, S, Peloso, G, Gustafsson, S, Kanoni, S, Ganna, A, Chen, J, Buchkovich, M, Mora, S, Beckmann, J, Bragg Gresham, J, Chang, H, Demirkan, A, Den Hertog, H, Do, R, Donnelly, L, Ehret, G, Esko, T, Feitosa, M, Ferreira, T, Fischer, K, Fontanillas, P, Fraser, R, Freitag, D, Gurdasani, D, Heikkilä, K, Hyppönen, E, Isaacs, A, Jackson, A, Johansson, A, Johnson, T, Kaakinen, M, Kettunen, J, Kleber, M, Li, X, Luan, J, Lyytikäinen, L, Magnusson, P, Mangino, M, Mihailov, E, Montasser, M, Müller Nurasyid, M, Nolte, I, O'Connell, J, Palmer, C, Perola, M, Petersen, A, Sanna, S, Saxena, R, Service, S, Shah, S, Shungin, D, Sidore, C, Song, C, Strawbridge, R, Surakka, I, Tanaka, T, Teslovich, T, Thorleifsson, G, Van den Herik, E, Voight, B, Volcik, K, Waite, L, Wong, A, Wu, Y, Zhang, W, Absher, D, Asiki, G, Barroso, I, Been, L, Bolton, J, Bonnycastle, L, Brambilla, P, Burnett, M, Cesana, G, Dimitriou, M, Doney, A, Döring, A, Elliott, P, Epstein, S, Eyjolfsson, G, Gigante, B, Goodarzi, M, Grallert, H, Gravito, M, Groves, C, Hallmans, G, Hartikainen, A, Hayward, C, Hernandez, D, Hicks, A, Holm, H, Hung, Y, Illig, T, Jones, M, Kaleebu, P, Kastelein, J, Khaw, K, Kim, E, Klopp, N, Komulainen, P, Kumari, M, Langenberg, C, Lehtimäki, T, Lin, S, Lindström, J, Loos, R, Mach, F, Mcardle, W, Meisinger, C, Mitchell, B, Müller, G, Nagaraja, R, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Ong, K, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Rader, D, Reilly, M, Ridker, P, Rivadeneira, F, Rudan, I, Ruokonen, A, Samani, N, Scharnagl, H, Seeley, J, Silander, K, Stancáková, A, Stirrups, K, Swift, A, Tiret, L, Uitterlinden, A, van Pelt, L, Vedantam, S, Wainwright, N, Wijmenga, C, Wild, S, Willemsen, G, Wilsgaard, T, Wilson, J, Young, E, Zhao, J, Adair, L, Arveiler, D, Assimes, T, Bandinelli, S, Bennett, F, Bochud, M, Boehm, B, Boomsma, D, Borecki, I, Bornstein, S, Bovet, P, Burnier, M, Campbell, H, Chakravarti, A, Chambers, J, Chen, Y, Collins, F, Cooper, R, Danesh, J, Dedoussis, G, de Faire, U, Feranil, A, Ferrières, J, Ferrucci, L, Freimer, N, Gieger, C, Groop, L, Gudnason, V, Gyllensten, U, Hamsten, A, Harris, T, Hingorani, A, Hirschhorn, J, Hofman, A, Hovingh, G, Hsiung, C, Humphries, S, Hunt, S, Hveem, K, Iribarren, C, Järvelin, M, Jula, A, Kähönen, M, Kaprio, J, Kesäniemi, A, Kivimaki, M, Kooner, J, Koudstaal, P, Krauss, R, Kuh, D, Kuusisto, J, Kyvik, K, Laakso, M, Lakka, T, Lind, L, Lindgren, C, Martin, N, März, W, Mccarthy, M, Mckenzie, C, Meneton, P, Metspalu, A, Moilanen, L, Morris, A, Munroe, P, Njølstad, I, Pedersen, N, Power, C, Pramstaller, P, Price, J, Psaty, B, Quertermous, T, Rauramaa, R, Saleheen, D, Salomaa, V, Sanghera, D, Saramies, J, Schwarz, P, Sheu, W, Shuldiner, A, Siegbahn, A, Spector, T, Stefansson, K, Strachan, D, Tayo, B, Tremoli, E, Tuomilehto, J, Uusitupa, M, van Duijn, C, Vollenweider, P, Wallentin, L, Wareham, N, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Boerwinkle, E, Thorsteinsdottir, U, Chasman, D, Rotter, J, Franks, P, Ripatti, S, Cupples, L, Sandhu, M, Rich, S, Boehnke, M, Deloukas, P, Kathiresan, S, Mohlke, K, Ingelsson, E, Abecasis, G, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Ehret, Georg Benedikt, Mach, François, Epidemiology, Surgery, Public Health, Ophthalmology, Neurology, Medical Microbiology & Infectious Diseases, Obstetrics & Gynecology, Internal Medicine, National Institute for Health Research, Global Lipids Genetics Consortium, Willer, Cristen, Sengupta, Sebanti, Peloso, Gina, Hypponen, Elina Tuulikki, and Abecasis, Gonçalo R
Subjects: Netherlands Twin Register (NTR), HOMEOSTASIS, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Blood lipids, Genome-wide association study, Type 2 diabetes, Coronary Artery Disease, 030204 cardiovascular system & hematology, Triglyceride, Coronary artery disease, chemistry.chemical_compound, 0302 clinical medicine, European Continental Ancestry Group/genetics, triglycerides, IDENTIFIES 13, 11 Medical and Health Sciences, African Continental Ancestry Group, 2. Zero hunger, Genetics, Genetics & Heredity, ddc:616, RISK, 0303 health sciences, Cholesterol, HDL/blood, PLASMA, Global Lipids Genetics Consortium, Cholesterol, HDL/blood/genetics, Lipid, Lipids, 3. Good health, LDL/blood, Triglycerides/blood, Lipids/blood/genetics, Cholesterol, Cholesterol, LDL/blood, DENSITY-LIPOPROTEIN CHOLESTEROL, CARDIOVASCULAR-DISEASE, HDL/blood, CORONARY-ARTERY-DISEASE, lipids (amino acids, peptides, and proteins), Life Sciences & Biomedicine, coronary artery disease, TRAITS, Human, Coronary Artery Disease/blood/genetics, Asian Continental Ancestry Group, Genotype, SUSCEPTIBILITY LOCI, European Continental Ancestry Group, Black People, HEART-DISEASE, Biology, Article, White People, lipids, 03 medical and health sciences, Coronary Artery Disease/blood, CORONARY-ARTERY-DISEASE DENSITY-LIPOPROTEIN CHOLESTEROL GENOME-WIDE ASSOCIATION HEART-DISEASE CARDIOVASCULAR-DISEASE SUSCEPTIBILITY LOCI IDENTIFIES 13 RISK GENE METAANALYSIS, Triglycerides/blood/genetics, Asian People, SDG 3 - Good Health and Well-being, Mendelian randomization, medicine, Humans, Asian Continental Ancestry Group/genetics, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Genotyping, Triglycerides, METAANALYSIS, 030304 developmental biology, Science & Technology, Lipids/blood, Cholesterol, HDL, cholesterol, African Continental Ancestry Group/genetics, Cholesterol, LDL, 06 Biological Sciences, medicine.disease, GENE, chemistry, Cholesterol, LDL/blood/genetics, Lipoprotein, Developmental Biology, Genome-Wide Association Study
Abstract: Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10 -8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research. © 2013 Nature America, Inc. All rights reserved.
Published: 2013
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17. Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks

Author: Albert Hofman, Megan L. Grove, Jennifer A. Brody, Adolfo Correa, Kim Lawson, Jose M. Ordovas, Yingchang Lu, André G. Uitterlinden, Riccardo E. Marioni, Nathan O. Stitziel, Oscar H. Franco, Yongmei Liu, Ingrid B. Borecki, Aron Y. Joon, Lindsay M. Reynolds, Ozren Polasek, Kelli K. Ryckman, Muredach P. Reilly, Johanna Jakobsdottir, Abbas Dehghan, L. Adrienne Cupples, Tamara B. Harris, Michael Griswold, Judy Wang, Christopher S. Carlson, Caroline Hayward, Leslie A. Lange, Stephen S. Rich, Kenneth Rice, Jacy R Crosby, Diego Ardissino, Charles Kooperberg, Gudny Eiriksdottir, Rachel H. Mackey, Ani Manichaikul, Martin Farrall, Jennifer E. Huffman, Albert V. Smith, Vilmundur Gudnason, Aniruddh P. Patel, Ruth J. F. Loos, Sumeet A. Khetarpal, Daniel J. Rader, Domenico Girelli, Eric Boerwinkle, Qunyuan Zhang, Valeska Redon, Anuj Goel, Cornelia M. van Duijn, Bruce M. Psaty, Ruth McPherson, Piera Angelica Merlini, Daniel Levy, Ian J. Deary, Christopher J. O'Donnell, Kurt Lohman, Josyf C. Mychaleckyj, Brian W. Davis, Mary F. Feitosa, Kent D. Taylor, James S. Pankow, Marju Orho-Melander, Alanna C. Morrison, Igor Rudan, Alexander P. Reiner, William E. Kraus, Ulrike Peters, Paul L. Auer, Paolo Zanoni, Svati H. Shah, Olle Melander, Jennifer G. Robinson, Joshua C. Bis, Erwin P. Bottinger, Mingyao Li, George Hindy, Omri Gottesman, Stefano Duga, Herman A. Taylor, Y.-D. Ida Chen, David S. Siscovick, Aaron Isaacs, Michael Y. Tsai, Sekar Kathiresan, James G. Wilson, Pamela J. Schreiner, Nicola Martinelli, Myriam Fornage, Serkalem Demissie, Lenore J. Launer, Hugh Watkins, Arend Voorman, Jerome I. Rotter, Jeanette M. Stafford, John M. Starr, Gina M. Peloso, Rosanna Asselta, Gail Davies, Rebecca D. Jackson, Epidemiology, and Internal Medicine
Subjects: Male, Blood lipids, Coronary Disease, 030204 cardiovascular system & hematology, Inbred C57BL, Cohort Studies, chemistry.chemical_compound, Mice, 0302 clinical medicine, Gene Frequency, Genotype, Genetics(clinical), Subtilisins, European Continental Ancestry Group/genetics, Exome, Genetics (clinical), Genetics, 0303 health sciences, Cholesterol, HDL/blood, 1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics, Middle Aged, 3. Good health, LDL/blood, Triglycerides/blood, Cholesterol, Phenotype, Cholesterol, LDL/blood, Genetic Code, HDL/blood, lipids (amino acids, peptides, and proteins), Female, Sequence Analysis, Microtubule-Associated Proteins, Adult, Sequence analysis, Black People, Biology, White People, Article, 03 medical and health sciences, Coronary Disease/blood, Animals, Humans, Allele frequency, Gene, Alleles, Genetic Association Studies, Triglycerides, 030304 developmental biology, Aged, PCSK9, Cholesterol, HDL, African Continental Ancestry Group/genetics, Genetic Variation, DNA, Cholesterol, LDL, Sequence Analysis, DNA, Microtubule-Associated Proteins/genetics, Subtilisins/genetics, Mice, Inbred C57BL, chemistry, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Linear Models
Abstract: Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121*], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.
Published: 2016

18. Variants in STAT5B Associate with Serum TC and LDL-C Levels

Author: Aaron Isaacs, Jan-Wilhelm Kornfeld, Thomas Meitinger, Josef M. Penninger, James F. Wilson, Richard Moriggl, Igor Rudan, Harry Campbell, J. Andrew Pospisilik, Veronika Sexl, Ulf Gyllensten, Cornelia M. van Duijn, Veronique Vitart, Peter P. Pramstaller, Andrew A. Hicks, and Epidemiology
Subjects: Male, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, STAT5B, Biochemistry, Transgenic, Mice, 0302 clinical medicine, Endocrinology, STAT5 Transcription Factor/genetics, Genotype, STAT5 Transcription Factor, European Continental Ancestry Group/genetics, 2. Zero hunger, Genetics, 0303 health sciences, Lipid Measurement, Single Nucleotide, Phenotype, LDL/blood, Cholesterol, Liver, Cholesterol, LDL/blood, 030220 oncology & carcinogenesis, Female, Signal transduction, Liver/metabolism, medicine.medical_specialty, Context (language use), Mice, Transgenic, Biology, Cholesterol/blood, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Genetic variation, medicine, Animals, Humans, Polymorphism, Genetic Association Studies, 030304 developmental biology, Biochemistry (medical), Genetic Variation, Cholesterol, LDL, Gene expression profiling
Abstract: Context: Known genetic variants influencing serum lipid levels do not adequately account for the observed population variability of these phenotypes. The GH/signal transducers and activators of transcription (STAT) signaling pathway is an evolutionary conserved system that exerts strong effects on metabolism, including that of lipids. Research Design and Methods: We analyzed the association of 11 single-nucleotide polymorphisms (SNP) spanning the STAT5B/STAT5A/STAT3 locus with serum lipid levels in six European populations (n = 5162 nondiabetic individuals). Results: After adjustment for age, sex, alcohol use, smoking, and body mass index, we identified STAT5B variants (rs8082391 and rs8064638) in novel association with total cholesterol (TC; P = 0.001 and P = 0.002) and low-density lipoprotein cholesterol (P = 0.002 and P = 0.004) levels. The minor alleles of these single-nucleotide polymorphisms were significantly enriched in hyperlipidemic individuals across the six discovery populations (P = 0.004 and P = 0.006). In transgenic mice deficient for hepatic STAT5A and STAT5B, reduced serum TC levels coincided with reduced hepatic cholesterol biosynthesis as demonstrated using gene expression profiling and pathway enrichment analysis. Conclusions: Genetic variants in STAT5B are associated with TC and low-density lipoprotein cholesterol levels among six populations. Mechanistically, STAT5B transcriptionally regulates hepatic cholesterol homeostasis.
Published: 2011

19. Haplotype analyses of the APOA5 gene in patients with familial combined hyperlipidemia

Author: Wu-Wei Zeng, Geesje M. Dallinga-Thie, Aaron Isaacs, Anton F. H. Stalenhoef, Cornelia M. van Duijn, Gerly M. van der Vleuten, Ewoud ter Avest, Philippa J. Talmud, Jacqueline de Graaf, Faculteit Medische Wetenschappen/UMCG, Epidemiology, Internal Medicine, Vascular Medicine, and Experimental Vascular Medicine
Subjects: Lipoproteins, LDL/blood, Male, Apolipoprotein B, Triglyceride level, Intima-media thickness, Hyperlipidemia, Familial Combined, Cardiovascular Diseases/blood, Vascular medicine and diabetes [UMCN 2.2], Hyperlipidemia, Familial Combined/blood, chemistry.chemical_compound, Polymorphism (computer science), Hyperlipidemia, Haplotype, Netherlands, Ultrasonography, Genetics, Cholesterol, HDL/blood, Cardiovascular diseases [NCEBP 14], biology, medicine.diagnostic_test, Homozygote, Remnant-like particle, Middle Aged, LDL/blood, Lipoproteins, LDL, APOA5 gene, Triglycerides/blood, Cholesterol, Carotid Arteries, Cardiovascular Diseases, HDL/blood, Population study, Molecular Medicine, Female, lipids (amino acids, peptides, and proteins), Adult, medicine.medical_specialty, Health aging / healthy living [IGMD 5], Familial combined hyperlipidemia, Lipoproteins, Risk Assessment, Genetic, Apolipoproteins A/genetics, Internal medicine, medicine, Humans, Familial Combined/blood, Genetic Predisposition to Disease, Polymorphism, Allele, Carotid Arteries/diagnostic imaging, Molecular Biology, Apolipoproteins A, Triglycerides, Polymorphism, Genetic, Cholesterol, HDL, medicine.disease, Endocrinology, chemistry, Haplotypes, Apolipoprotein A-V, biology.protein, Lipid profile
Abstract: Contains fulltext : 53623.pdf (Publisher’s version ) (Closed access) BACKGROUND: Familial combined hyperlipidemia (FCH) is the most common genetic lipid disorder with an undefined genetic etiology. Apolipoprotein A5 gene (APOA5) variants were previously shown to contribute to FCH. The aim of the present study was to evaluate the association of APOA5 variants with FCH and its related phenotypes in Dutch FCH patients. Furthermore, the effects of variants in the APOA5 gene on carotid intima-media thickness (IMT) and cardiovascular disease (CVD) were examined. MATERIALS AND METHODS: The study population consisted of 36 Dutch families, including 157 FCH patients. Two polymorphisms in the APOA5 gene (-1131T>C and S19W) were genotyped. RESULTS: Haplotype analysis of APOA5 showed an association with FCH (p=0.029), total cholesterol (p=0.031), triglycerides (p
Published: 2007

20. Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro

Author: Tiina Solakivi, Terho Lehtimäki, Seppo T. Nikkari, Olli Jaakkola, Tarja Kunnas, Jaana Renko, Biolääketieteellisen teknologian yksikkö - Institute of Biomedical Technology, Lääketieteen yksikkö - School of Medicine, and University of Tampere
Subjects: Lipoproteins, LDL/blood, Lipoprotein modification, medicine.medical_specialty, Lipid Peroxidation/genetics, Genotype, Biolääketieteet - Biomedicine, FADS2, Lipoproteins, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Biology, In Vitro Techniques, Linoleoyl-CoA Desaturase, chemistry.chemical_compound, Eicosapentaenoic Acid/blood, Unsaturated/blood, Endocrinology, Internal medicine, medicine, Humans, Arachidonic Acid/blood, Lipoprotein oxidation, Fatty Acids, Unsaturated/blood, Genetic Association Studies, Sequence Deletion, Biochemistry, medical, Arachidonic Acid, Research, Biochemistry (medical), Fatty Acids, Linoleoyl-CoA Desaturase/genetics, Eicosapentaenoic acid, Delta-6-desaturase, LDL/blood, Lipoproteins, LDL, Fatty acid desaturase, Eicosapentaenoic Acid, Biochemistry, chemistry, Fatty Acids, Unsaturated, biology.protein, lipids (amino acids, peptides, and proteins), Lipid Peroxidation, Docosapentaenoic acid, Linoleoyl-CoA desaturase, Oxidation-Reduction
Abstract: Background Oxidative modification of low-density lipoprotein (LDL) is a key event in the oxidation hypothesis of atherogenesis. We have previously shown that HDL does not protect LDL from oxidation in vitro, but is in fact oxidized fastest of all lipoproteins due to its rich polyunsaturated fatty acid (PUFA) composition, which is oxidation promoting. Evidence has accumulated to show that in addition to diet, common polymorphisms in the fatty acid desaturase (FADS) gene cluster have very marked effects on human PUFA status. There is a deletion [T/-] in the promoter region of the Δ6 –desaturase gene (FADS2, rs 3834458), which has a direct inhibitory influence on production of PUFA from linoleic and alpha-linolenic acid. To investigate the possible role of rs 3834458 in lipoprotein modification, oxidation of LDL with HDL2 or HDL3 were analyzed from plasma of 58 free-living individuals. Results Total eicosapentaenoic acid and arachidonic acid were significantly decreased in plasma from the 10 subjects homozygous for the deletion in FADS2 rs 3834458. When the isolated LDL and HDL2 were subjected to Cu2+-induced oxidation, these subjects showed decreased rate of appearance (p = 0.027) and the final concentration of conjugated dienes (p = 0.033) compared to the other genotypes. For oxidation of LDL with HDL3, the final concentration of conjugated dienes was also significantly decreased in subjects with [−/−] compared with [T/T] and [T/-] (p = 0.034). Conclusion We conclude that FADS2 genotype may play a role in peroxidation susceptibility of lipoproteins.
Published: 2013

21. Polyphenol-rich cranberry juice has a neutral effect on endothelial function but decreases the fraction of osteocalcin-expressing endothelial progenitor cells

Author: Flammer, A J, Martin, E A, Gossl, M, Widmer, R J, Lennon, R J, Sexton, J A, Loeffler, D, Khosla, S, Lerman, L O, Lerman, A, University of Zurich, and Lerman, A
Subjects: Adult, Male, Endothelial Cells/cytology/*drug effects/metabolism, Stem Cells/cytology/*drug effects/metabolism, Lipoproteins, 610 Medicine & health, Double, Vascular Cell Adhesion Molecule, Risk Factors, 6/blood, Leukocytes, Humans, Mononuclear/cytology/drug effects/metabolism, Biological Markers/blood, Polyphenols/*administration & dosage, Blind Method, 1/blood, Aged, Reactive Protein/analysis/metabolism, Beverages/*analysis, 2701 Medicine (miscellaneous), Interleukin, Middle Aged, Flow Cytometry, alpha/blood, Vaccinium macrocarpon/*chemistry, Intercellular Adhesion Molecule, LDL/blood, 10209 Clinic for Cardiology, 2916 Nutrition and Dietetics, Female, Tumor Necrosis Factor, Cardiovascular Diseases/prevention & control, Osteocalcin/genetics/*metabolism
Published: 2013

22. Effecten van kortdurend gebruik van meervoudig onverzadigde vetzuren van het omega-3-type bij personen met hypertriglyceridemie

Subjects: Adult, Male, Linoleic Acids/therapeutic use, Middle Aged, Cholesterol/blood, LDL/blood, Linoleic Acid, Triglycerides/blood, Cholesterol, Double-Blind Method, Fish Oils/therapeutic use, Hypertriglyceridemia/drug therapy, Humans, lipids (amino acids, peptides, and proteins), Female, Prospective Studies
Abstract: OBJECTIVE: To study the effect of omega-3 polyunsaturated fatty acid supplementation on lipid profile in hypertriglyceridaemic patients. SETTING: General practice. DESIGN: Prospective, double blind study of 12 weeks' duration. PATIENTS AND METHODS: Eight patients received fish oil (1800 mg C20: 5 omega-3 eicosapentaenoic acid (EPA) and 1200 mg C22:6 omega-3 docosahexaenoic acid (DHA). Nine patients received corn oil (3000 mg C18: 2 omega-6 linoleic acid daily). RESULTS: Lipid profile analysis showed a decrease in triglyceride levels after fish oil supplementation. An unexpected and unexplained finding was the rise in total cholesterol and LDH cholesterol with corn oil supplementation. CONCLUSION: Fish oil causes a decrease in triglyceride levels in hypertriglyceridaemic patients.
Published: 1992

23. Parabolic relationship between plasma triacylglycerols and LDL-cholesterol in familial combined hyperlipidaemia: the multiple-type hyperlipidaemia explained?

Author: Anton F. H. Stalenhoef, Marleen M.J. van Greevenbroek, Coen D.A. Stehouwer, Jacqueline de Graaf, Ewoud ter Avest, Martijn C. G. J. Brouwers, Anna M. Georgieva, Carla J.H. van der Kallen, Tjerk W.A. de Bruin, and Faculteit Medische Wetenschappen/UMCG
Subjects: Adult, Male, medicine.medical_specialty, Health aging / healthy living [IGMD 5], Apolipoprotein B, Hyperlipidemia, Familial Combined, Cardiovascular Diseases/blood, Vascular medicine and diabetes [UMCN 2.2], Group A, Group B, Hyperlipidemia, Familial Combined/blood, Coronary artery disease, Cohort Studies, Sex Factors, Internal medicine, Blood plasma, Medicine, Humans, Familial Combined/blood, Triglycerides, Apolipoproteins B, biology, Cardiovascular diseases [NCEBP 14], business.industry, nutritional and metabolic diseases, General Medicine, Cholesterol, LDL, Middle Aged, medicine.disease, LDL/blood, Apolipoproteins B/blood, Triglycerides/blood, Cholesterol, Hyperlipidemia, Endocrinology, Genetic defects of metabolism [UMCN 5.1], Cholesterol, LDL/blood, Cardiovascular Diseases, Cohort, biology.protein, lipids (amino acids, peptides, and proteins), Female, business, Biomarkers/blood, Biomarkers, Cohort study, Lipoprotein, Follow-Up Studies
Abstract: Contains fulltext : 69040.pdf (Publisher’s version ) (Open Access) FCHL (familial combined hyperlipidaemia) is a highly prevalent genetic lipid disorder that accounts for a substantial number of premature cardiovascular events. To date, FCHL has been complicated by the different lipid phenotypes that are present within one family and one individual patient over time. In the present study, we hypothesized that a parabolic relationship between plasma triacylglycerols (triglycerides) and LDL (low-density lipoprotein)-cholesterol can explain this so-called 'multiple-type hyperlipidaemia' in FCHL. Our hypothesis was tested in two well-documented FCHL cohorts [Maastricht (n=145) and Nijmegen (n=299)] that were followed over a 5-year interval. Three groups were constructed depending on plasma triacylglycerols: group A (individuals with both measurements below 1.5 mmol/l), group B (one measurement below and one measurement above 1.5 mmol/l) and group C (both measurement above 1.5 mmol/l). In both male, but not female, cohorts, a significant positive relationship between plasma triacylglycerols and LDL-cholesterol was observed in group A (P=0.02 for Maastricht cohort and P=0.001 for the Nijmegen cohort), a significant negative relationship in group C (P=0.01 for Maastricht cohort and P=0.02 for the Nijmegen cohort), and a relationship intermediate to group A and C in group B. In contrast, both apoB (apolipoprotein B) levels and the prevalence of cardiovascular disease were related with plasma triacylglycerols in a more linear fashion. In conclusion, a parabolic relationship between plasma triacylglycerols and LDL-cholesterol explains the 'multiple-type hyperlipidaemia' in FCHL. In addition, the linear relationship between triacylglycerols and both apoB levels and the prevalence of cardiovascular disease substantiate the use of apoB instead of LDL-cholesterol in the diagnosis of FCHL and the prediction of cardiovascular disease.
Published: 2007

24. High plasma level of remnant-like particles cholesterol in familial combined hyperlipidemia

Author: Gerly M. van der Vleuten, Ewoud ter Avest, Anton F. H. Stalenhoef, Geesje M. Dallinga-Thie, Jacqueline de Graaf, Vascular Medicine, Experimental Vascular Medicine, Internal Medicine, and Faculteit Medische Wetenschappen/UMCG
Subjects: Male, Endocrinology, Diabetes and Metabolism, Cholesterol, VLDL, Clinical Biochemistry, Hyperlipidemia, Familial Combined, Vascular medicine and diabetes [UMCN 2.2], Biochemistry, Hyperlipidemia, Familial Combined/blood, Body Mass Index, chemistry.chemical_compound, Endocrinology, Reference Values, Hyperlipidemia, Body Size, VLDL/blood, Cholesterol, HDL/blood, Cardiovascular diseases [NCEBP 14], medicine.diagnostic_test, Cholesterol, VLDL/blood, Middle Aged, LDL/blood, Cholesterol, Cholesterol, LDL/blood, Cardiovascular Diseases, HDL/blood, Female, Cholesterol/analogs & derivatives, Adult, medicine.medical_specialty, Health aging / healthy living [IGMD 5], Context (language use), Internal medicine, medicine, Humans, Familial Combined/blood, Risk factor, Spouses, Triglyceride, Cardiovascular Diseases/epidemiology, Cholesterol, HDL, Biochemistry (medical), Cholesterol, LDL, Odds ratio, medicine.disease, chemistry, Lipid profile, Lipoprotein
Abstract: Contains fulltext : 53463.pdf ( ) (Closed access) CONTEXT: The traditional lipid and lipoprotein levels in patients with familial combined hyperlipidemia (FCH) are relatively mildly elevated and do not fully explain the increased risk of cardiovascular disease (CVD). In other populations, high remnant-like particles cholesterol (RLP-C) levels are an independent risk factor for CVD. OBJECTIVE: The objective of the study was to investigate whether plasma RLP-C concentrations are elevated in patients with FCH and contribute to the increased prevalence of CVD. DESIGN, SETTING, PARTICIPANTS: In this cross-sectional study, we studied RLP-C levels in 37 FCH families comprising 582 subjects, of whom 134 subjects were diagnosed FCH based on total cholesterol, triglyceride, and apolipoprotein-B levels. Plasma RLP-C concentrations were determined using an immune-separation technique. RESULTS: For both men and women, the mean plasma RLP-C concentration (mmol/liter) was 2-fold elevated in FCH patients [0.59 (0.54-0.66) and 0.40 (0.37-0.43), respectively] compared with both normolipidemic relatives [0.27 (0.26-0.29) in male and 0.22 (0.21-0.23) in female, all P
Published: 2007

25. Effect of aging and obesity on the expression of dyslipidaemia in children from families with familial combined hyperlipidaemia

Author: Jacqueline de Graaf, Anton F. H. Stalenhoef, Ewoud ter Avest, Allan D. Sniderman, Sebastian J.H. Bredie, Albert Wiegman, Faculteit Medische Wetenschappen/UMCG, and Paediatric Metabolic Diseases
Subjects: Male, Aging, Very low-density lipoprotein, Lipoproteins, VLDL/blood, Apolipoprotein B, Hyperlipidemia, Familial Combined, Adipose tissue, Vascular medicine and diabetes [UMCN 2.2], Lipoproteins, VLDL, Body Mass Index, chemistry.chemical_compound, Familial Combined/metabolism, Hyperlipidemia, Obesity/metabolism, Dyslipidemias/metabolism, Medicine, VLDL/blood, Cholesterol, HDL/blood, biology, Cardiovascular diseases [NCEBP 14], General Medicine, LDL/blood, Triglycerides/blood, Cholesterol, Phenotype, Cholesterol, LDL/blood, HDL/blood, Regression Analysis, Female, lipids (amino acids, peptides, and proteins), Adult, medicine.medical_specialty, Health aging / healthy living [IGMD 5], Adolescent, Offspring, Lipoproteins, Cholesterol/blood, Insulin resistance, Internal medicine, Humans, Obesity, Life Style, Triglycerides, Apolipoproteins B, Dyslipidemias, business.industry, Cholesterol, HDL, nutritional and metabolic diseases, Cholesterol, LDL, Hyperlipidemia, Familial Combined/metabolism, medicine.disease, Aging/physiology, Apolipoproteins B/blood, Endocrinology, chemistry, Case-Control Studies, biology.protein, Insulin Resistance, business, Lipoprotein, Follow-Up Studies
Abstract: Contains fulltext : 51880.pdf (Publisher’s version ) (Closed access) The aim of the present study was to delineate the mechanism(s) responsible for the increased secretion of VLDL (very-low-density lipoprotein) particles in patients with FCH (familial combined hyperlipidaemia). In 194 young adults (1.5 mmol/l and/or small-dense LDL, were observed only sporadically. After the 5-year follow-up, BMI increased in both groups, and this increase was associated with changes in apoB (r=0.27, P
Published: 2007

26. Combined lower body endurance and upper body resistance training improves performance and health parameters in healthy active elderly

Author: Verney, Julien, Kadi, Fawzi, Saafi, Mohamed A., Piehl-Aulin, Karin, Denis, Christian, Verney, Julien, Kadi, Fawzi, Saafi, Mohamed A., Piehl-Aulin, Karin, and Denis, Christian
Abstract: We investigated the effects of combined lower body (LB) endurance and upper body (UB) resistance training on endurance, strength, blood lipid profile and body composition in active older men. Ten healthy still active men (73+/-4 years, V(O2) peak: 36 (31-41) ml min-1 kg-1) were tested before and after 14 weeks of combined training (3 times week-1). Training consisted of 3x12 min of high intensity interval training on a bicycle for endurance interspersed by 3x12 min of UB resistance exercises. V(O2) peak during leg cycling and arm cranking, isokinetic torque of knee extensor and shoulder abductor and the cross-sectional area (CSA) of several muscles from UB and LB were measured. Sagittal abdominal diameter (SAD) and abdominal fat area were measured on MRI scans. Total body composition was assessed by hydrostatic weighing (HW) and dual-energy X-ray absorptiometry (DEXA). Blood lipid profile was assessed before and after training. By the end of the training period, V(O2) peak (l min-1) increased significantly by 9 and 16% in leg cycling and arm cranking tests, respectively. Maximal isokinetic torque increased both for the knee extensor and shoulder abductor muscle groups. CSA increased significantly in deltoid muscle. Percentage of body fat decreased by 1.3% (P<0.05) and abdominal fat and SAD decreased by 12 and 6%, respectively (P<0.01). There was also a significant decrease in total cholesterol and low-density lipoprotein. Thus, combined LB endurance and UB resistance training can improve endurance, strength, body composition and blood lipid profile even in healthy active elderly.
Published: 2006
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26 results on '"LDL/blood"'

1. Prehypertension A Meta-Analysis of the Epidemiology, Risk Factors, and Predictors of Progression

2. Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease

3. Comparison Between Non-High-Density Lipoprotein Cholesterol and Low-Density Lipoprotein Cholesterol to Estimate Cardiovascular Risk Using a Multivariate Model.

4. Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration

5. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study

6. The association between exposure to different aspects of shift work and metabolic risk factors in health care workers, and the role of chronotype

7. Association of Triglyceride-Lowering LPL Variants and LDL-C–Lowering LDLR Variants With Risk of Coronary Heart Disease

8. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

9. Shaping of Peripheral T Cell Responses by Lymphatic Endothelial Cells

10. Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

11. Implementation Strategies to Improve Non-HDL-Cholesterol Goal Attainment.

12. Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III study

13. Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study

14. Common variants associated with plasma triglycerides and risk for coronary artery disease

15. Risk Scores of Common Genetic Variants for Lipid Levels Influence Atherosclerosis and Incident Coronary Heart Disease

16. Discovery and refinement of loci associated with lipid levels

17. Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks

18. Variants in STAT5B Associate with Serum TC and LDL-C Levels

19. Haplotype analyses of the APOA5 gene in patients with familial combined hyperlipidemia

20. Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro

21. Polyphenol-rich cranberry juice has a neutral effect on endothelial function but decreases the fraction of osteocalcin-expressing endothelial progenitor cells

22. Effecten van kortdurend gebruik van meervoudig onverzadigde vetzuren van het omega-3-type bij personen met hypertriglyceridemie

23. Parabolic relationship between plasma triacylglycerols and LDL-cholesterol in familial combined hyperlipidaemia: the multiple-type hyperlipidaemia explained?

24. High plasma level of remnant-like particles cholesterol in familial combined hyperlipidemia

25. Effect of aging and obesity on the expression of dyslipidaemia in children from families with familial combined hyperlipidaemia

26. Combined lower body endurance and upper body resistance training improves performance and health parameters in healthy active elderly

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26 results on '"LDL/blood"'

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