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[PMID]:28463860
[Au] Autor:Graham CA; Latten MJ; Hart PJ
[Ad] Endereço:aMolecular Diagnostics, Randox Laboratories Ltd., Crumlin bRegional Genetics Centre, Belfast City Hospital, Belfast Health and Social Care Trust, Belfast, UK.
[Ti] Título:Molecular diagnosis of familial hypercholesterolaemia.
[So] Source:Curr Opin Lipidol;28(4):313-320, 2017 Aug.
[Is] ISSN:1473-6535
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE OF REVIEW: Familial hypercholesterolaemia is a hereditary disorder of lipoprotein metabolism which causes a lifelong increase in LDL-C levels resulting in premature coronary heart disease. The present review looks at some of the recent literature on how molecular methods can be used to assist in the definitive diagnosis of familial hypercholesterolaemia in a range of patient groups. RECENT FINDINGS: Several recent studies have shown that the prevalence of clinical familial hypercholesterolaemia is higher than previously thought at 1/200 to 1/300, and that 2-5% of patients presenting with early myocardial infarction can be found to have a familial hypercholesterolaemia mutation. The present review then examines different approaches to molecular testing for familial hypercholesterolaemia including point mutation panels versus next-generation sequencing gene panels, and the range of genes tested by some of those panels. Finally, we review the recent evidence for polygenic hypercholesterolaemia within clinically defined familial hypercholesterolaemia patient populations. SUMMARY: To identify patients with familial hypercholesterolaemia within clinically selected patient groups efficiently, a clinical scoring system should be combined with a molecular testing approach for mutations and for polygenic LDL-C single-nucleotide polymorphisms. Alternatively, a population screening methodology may be appropriate, using mutation testing at an early age before significant atherosclerosis has begun. The precise molecular testing method chosen may depend on the clinical presentation of the patient, and/or the population from which they arise.
[Mh] Termos MeSH primário: Hiperlipoproteinemia Tipo II/diagnóstico
Técnicas de Diagnóstico Molecular/métodos
[Mh] Termos MeSH secundário: Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Hiperlipoproteinemia Tipo II/genética
Mutação Puntual
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1097/MOL.0000000000000430


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[PMID]:29419393
[Au] Autor:Ford TJ; Rocchiccioli P
[Ad] Endereço:British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
[Ti] Título:A keen eye for risk.
[So] Source:BMJ;360:j5884, 2018 02 01.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Arco Senil/diagnóstico
Doenças da Córnea/diagnóstico
Doença da Artéria Coronariana/diagnóstico
Hiperlipoproteinemia Tipo II/diagnóstico
Receptores de LDL/genética
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/administração & dosagem
Anticorpos Monoclonais/uso terapêutico
Anticolesterolemiantes/administração & dosagem
Anticolesterolemiantes/uso terapêutico
Arco Senil/etiologia
Colesterol/sangue
Doenças da Córnea/etiologia
Doença da Artéria Coronariana/complicações
Doença da Artéria Coronariana/etiologia
Feminino
Seres Humanos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
Hiperlipoproteinemia Tipo II/sangue
Hiperlipoproteinemia Tipo II/tratamento farmacológico
Hiperlipoproteinemia Tipo II/genética
Injeções Subcutâneas
Meia-Idade
Mutação
Pró-Proteína Convertase 9/antagonistas & inibidores
Xantomatose/diagnóstico
Xantomatose/etiologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Anticholesteremic Agents); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Receptors, LDL); 97C5T2UQ7J (Cholesterol); EC 3.4.21.- (PCSK9 protein, human); EC 3.4.21.- (Proprotein Convertase 9); LKC0U3A8NJ (evolocumab)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180209
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.j5884


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[PMID]:29335316
[Au] Autor:Garrett EL; Chodhari R
[Ad] Endereço:University College London Hospital Trust, London NW1 2BU, UK.
[Ti] Título:Integrated lipid clinics for adults and children with familial hypercholesterolaemia.
[So] Source:BMJ;360:k75, 2018 01 15.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Instituições de Assistência Ambulatorial
Hiperlipoproteinemia Tipo II/diagnóstico
Hiperlipoproteinemia Tipo II/terapia
[Mh] Termos MeSH secundário: Adulto
Criança
Seres Humanos
Reino Unido
[Pt] Tipo de publicação:LETTER
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.k75


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[PMID]:28470529
[Au] Autor:Thormählen AS; Runz H
[Ad] Endereço:Institute of Human Genetics, University of Heidelberg, Heidelberg, 69120, Germany.
[Ti] Título:Systematic Cell-Based Phenotyping of Missense Alleles.
[So] Source:Methods Mol Biol;1601:215-228, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sequencing of the protein-coding genome, the exome, has proven powerful to unravel links between genetic variation and disease for both Mendelian and complex conditions. Importantly, however, the increasing number of sequenced human exomes and mapping of disease-associated alleles is accompanied by a simultaneous, yet exponential increase in the overall number of rare and low frequency alleles identified. For most of these novel alleles, biological consequences remain unknown since reliable experimental approaches to better characterize their impact on protein function are only slowly emerging.Here we review a scalable, cell-based strategy that we have recently established to systematically profile the biological impact of rare and low frequency missense variants in vitro. By applying this approach to missense alleles identified through cohort-level exome sequencing in the low-density lipoprotein receptor (LDLR) we are able to distinguish rare alleles that predispose to familial hypercholesterolemia and myocardial infarction from alleles without obvious impact on LDLR levels or functions. We propose that systematic implementation of such and similar strategies will significantly advance our understanding of the protein-coding human genome and how rare and low frequency genetic variation impacts on health and disease.
[Mh] Termos MeSH primário: Alelos
Hiperlipoproteinemia Tipo II/genética
Mutação de Sentido Incorreto
Infarto do Miocárdio/genética
Receptores de LDL/genética
Receptores de LDL/metabolismo
[Mh] Termos MeSH secundário: DNA Complementar/química
Exoma/genética
Predisposição Genética para Doença
Proteínas de Fluorescência Verde/química
Células HeLa
Seres Humanos
Fenótipo
RNA Interferente Pequeno
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Complementary); 0 (LDLR protein, human); 0 (RNA, Small Interfering); 0 (Receptors, LDL); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6960-9_17


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[PMID]:29241886
[Au] Autor:Cheng WH; Gaudette É; Goldman DP
[Ad] Endereço:Schaeffer Center for Health Policy and Economics, University of Southern California Price School and School of Pharmacy, Los Angeles, CA, USA. Electronic address: weihanch@usc.edu.
[Ti] Título:PCSK9 Inhibitors Show Value for Patients and the US Health Care System.
[So] Source:Value Health;20(10):1270-1278, 2017 12.
[Is] ISSN:1524-4733
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved by the US Food and Drug Administration (FDA) as cholesterol-lowering therapies for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease. OBJECTIVES: To estimate the long-term health and economic value of PCSK9 inhibitors for Americans (51 years and older). METHODS: We conducted simulations using the Future Elderly Model, an established dynamic microsimulation model to project the lifetime outcomes for the US population aged 51 years and older. Health effects estimates and confidence intervals from published meta-analysis studies were used to project changes in life expectancy, quality-adjusted life-years, and lifetime medical spending resulting from the use of PCSK9 inhibitors. We considered two treatment scenarios: 1) current FDA eligibility and 2) an extended eligibility scenario that includes patients with no pre-existing cardiovascular disease but at high risk. We assumed that the price of PCSK9 inhibitors was discounted by 35% in the first 12 years and by 57% thereafter, with gradual uptake of the drug in eligible populations. RESULTS: Use of PCSK9 inhibitors by individuals covered by current FDA approval would extend life expectancy at the age of 51 years by an estimated 1.1 years and would yield a lifetime net value of $5800 per person. If use was extended to those at high risk for cardiovascular disease, PCSK9 inhibitors would generate a lifetime net benefit of $14,100 per person. CONCLUSIONS: Expanded access to PCSK9 inhibitors would offer positive long-term net value for patients and the US health care system at the current discounted prices.
[Mh] Termos MeSH primário: Anticolesterolemiantes/uso terapêutico
Aterosclerose/tratamento farmacológico
Simulação por Computador
Hiperlipoproteinemia Tipo II/tratamento farmacológico
Pró-Proteína Convertase 9/antagonistas & inibidores
[Mh] Termos MeSH secundário: Idoso
Anticolesterolemiantes/economia
Anticolesterolemiantes/farmacologia
Aterosclerose/economia
Análise Custo-Benefício
Assistência à Saúde/economia
Aprovação de Drogas
Definição da Elegibilidade
Seres Humanos
Hiperlipoproteinemia Tipo II/economia
Expectativa de Vida
Meia-Idade
Anos de Vida Ajustados por Qualidade de Vida
Estados Unidos
United States Food and Drug Administration
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Anticholesteremic Agents); EC 3.4.21.- (PCSK9 protein, human); EC 3.4.21.- (Proprotein Convertase 9)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE


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[PMID]:29172973
[Au] Autor:Menzin J; Aggarwal J; Boatman B; Yu J; Stern K; Harrison DJ; Patel JG
[Ad] Endereço:1 Boston Health Economics, Waltham, Massachusetts.
[Ti] Título:Ezetimibe Use and LDL-C Goal Achievement: A Retrospective Database Analysis of Patients with Clinical Atherosclerotic Cardiovascular Disease or Probable Heterozygous Familial Hypercholesterolemia.
[So] Source:J Manag Care Spec Pharm;23(12):1270-1276, 2017 Dec.
[Is] ISSN:2376-1032
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Ezetimibe is recommended by clinical practice guidelines as a second-line therapy for lowering low-density lipoprotein cholesterol (LDL-C) levels, but little is known about its use and effectiveness in real-world populations. OBJECTIVE: To understand the real-world impact of adding or switching to ezetimibe on LDL-C goal achievement in patients with clinical atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH). METHODS: Patients aged ≥ 18 years with an LDL-C measurement available between January 1, 2013, and June 30, 2014, were identified using the Inovalon MORE database; this included commercial, health insurance exchange, Medicare Advantage, and managed Medicaid patients. The index date was the date of the first LDL-C measurement. Patients were required to have evidence of clinical ASCVD or probable HeFH based on ICD-9-CM codes and ≥ 1 outpatient pharmacy claim for a statin in the 1-year pre-index period, as well as continuous medical and pharmacy coverage for 1 year pre- and post-index. Patients who added ezetimibe to existing statin therapy or switched to ezetimibe within 90 days post-index LDL-C measurement were identified in order to replicate the typical time a clinician takes to assess the use of ezetimibe. The primary outcome was the proportion of patients who met the LDL-C goal of < 70 mg/dL within the follow-up period. LDL-C goal achievement was evaluated by baseline LDL-C level groupings: < 70 mg/dL, 70-99 mg/dL, 100-129 mg/dL, or ≥ 130 mg/dL; and across 4 patient diagnosis categories: all patients, ASCVD only, probable HeFH only, and ASCVD and probable HeFH. Descriptive analyses were reported. Categorical variables were summarized as the number of and corresponding percentage of patients. Continuous variables were presented as the mean and SD of the number of observations and median and range where appropriate. RESULTS: Of 125,330 patients who met selection criteria, mean age was 70.1 (SD = 9.9) years and mean LDL-C baseline was 90.7 (SD = 34.0) mg/dL. Over one half of patients (70%) were receiving statin therapy. Within the post-index time frame, 1.05% (n = 1,309) of patients added or switched to ezetimibe. Of these, 26% achieved LDL-C goal during the 90-day follow-up (59.5% did not achieve goal and 14.4% did not have a follow-up lab value). Therapeutic targets were reached by 30% of patients with baseline LDL-C levels of 70-99 mg/dL; 14% of those with baseline LDL-C of 100-129 mg/dL; and 7% of those with baseline LDL-C of ≥ 130 mg/dL. Achievement of LDL-C goals also varied by baseline diagnosis category. CONCLUSIONS: The addition of or switch to ezetimibe therapy was associated with a relatively small percentage of LDL-C goal achievement (< 70 mg/dL) in patients with clinical ASCVD and/or HeFH, even among patients with baseline LDL-C between 70 and 99 mg/dL. To provide superior individualized care for patients with hyperlipidemia, there is a potential role for newer therapies in lipid lowering, such as PCSK9 inhibitors, in appropriate high-risk populations. DISCLOSURES: This study was sponsored by Amgen. Menzin, Yu, and Stern are employees of Boston Health Economics, which was contracted by Amgen to perform this study. Aggarwal is a former employee of Boston Health Economics. Boatman, Patel, and Harrison are employees and stockholders of Amgen. Study concept and design were contributed by Menzin, Aggarwal, Harrison, and Patel. Aggarwal, Stern, and Yu collected the data. Data interpretation was performed by Aggarwal, Harrison, Patel, and Boatman. The manuscript was written and revised primarily by Aggarwal, with assistance from the other authors.
[Mh] Termos MeSH primário: Anticolesterolemiantes/uso terapêutico
Aterosclerose/tratamento farmacológico
Ezetimiba/uso terapêutico
Hiperlipoproteinemia Tipo II/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Anticolesterolemiantes/administração & dosagem
LDL-Colesterol/sangue
Quimioterapia Combinada
Ezetimiba/administração & dosagem
Feminino
Seguimentos
Seres Humanos
Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem
Masculino
Meia-Idade
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Cholesterol, LDL); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); EOR26LQQ24 (Ezetimibe)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.18553/jmcp.2017.16414


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[PMID]:29228028
[Au] Autor:Shu H; Chi J; Li J; Zhang W; Lv W; Wang J; Deng Y; Hou X; Wang Y
[Ad] Endereço:Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
[Ti] Título:A novel indel variant in LDLR responsible for familial hypercholesterolemia in a Chinese family.
[So] Source:PLoS One;12(12):e0189316, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevation of serum cholesterol bound to low-density lipoprotein. Mutations in LDLR are the major factors responsible for FH. In this study, we recruited a four-generation Chinese family with FH and identified the clinical features of hypercholesterolemia. All affected individuals shared a novel indel mutation (c.1885_1889delinsGATCATCAACC) in exon 13 of LDLR. The mutation segregated with the hypercholesterolemia phenotype in the family. To analyze the function of the indel, we established stable clones of mutant and wild-type LDLR in Hep G2 cells. The mutant LDLR was retained in the endoplasmic reticulum (ER) and failed to glycosylate via the Golgi. Moreover, the membrane LDLR was reduced and lost the ability to take up LDL. Our data also expand the spectrum of known LDLR mutations.
[Mh] Termos MeSH primário: Hiperlipoproteinemia Tipo II/genética
Mutação INDEL
Receptores de LDL/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Retículo Endoplasmático/metabolismo
Feminino
Células Hep G2
Seres Humanos
Masculino
Meia-Idade
Transporte Proteico
Receptores de LDL/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, LDL)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189316


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[PMID]:28456682
[Au] Autor:Paquette M; Chong M; Thériault S; Dufour R; Paré G; Baass A
[Ad] Endereço:Nutrition, Metabolism and Atherosclerosis Clinic, Institut de recherches cliniques de Montréal, Québec, Canada.
[Ti] Título:Polygenic risk score predicts prevalence of cardiovascular disease in patients with familial hypercholesterolemia.
[So] Source:J Clin Lipidol;11(3):725-732.e5, 2017 May - Jun.
[Is] ISSN:1933-2874
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Although familial hypercholesterolemia (FH) is a severe monogenic disease, it has been shown that clinical risk factors and common genetic variants can modify cardiovascular disease (CVD) risk. OBJECTIVE: The aim of the study was to evaluate the polygenic contribution to lipid traits and CVD in FH using genetic risk scores (GRSs). METHODS: Among the 20,434 subjects attending the lipid clinic, we identified and included 725 individuals who carried an FH causing mutation in this retrospective cohort study. We evaluated the association of GRSs for several traits including coronary artery disease (CAD; GRS ) as well as plasma concentrations of low-density lipoprotein cholesterol (LDL-C; GRS ), high-density lipoprotein cholesterol (GRS ) and triglycerides (GRS ). RESULTS: A total of 32% (n = 231) of FH subjects presented a CVD event before their first visit. Patients in the highest GRS tertile presented an LDL-C 0.4 mmol/L (15.5 mg/dL) higher than the subjects in the lowest tertile (P = .01). The GRS was strongly associated with CVD events (odds ratio 1.80; 95% confidence interval 1.14-2.85; P = .01) even after adjustment for cardiovascular risk factors. Compared with subjects in the first tertile, those in the third GRS tertile had a significantly higher prevalence of events (40.9% vs 24.7%, P < .0001) and a significantly higher number of events (average 0.97 vs 0.57 [P = .0001] events per individual). CONCLUSION: These results indicate that even in the context of a severe monogenic disease such as FH, common genetic variants can significantly modify the disease phenotype. The use of the 192-SNPs GRS may refine CVD risk prediction in FH patients and this could lead to a more personalized approach to therapy.
[Mh] Termos MeSH primário: Doenças Cardiovasculares/complicações
Variação Genética
Hiperlipoproteinemia Tipo II/complicações
Hiperlipoproteinemia Tipo II/genética
[Mh] Termos MeSH secundário: Adulto
Doenças Cardiovasculares/epidemiologia
Feminino
Seres Humanos
Hiperlipoproteinemia Tipo II/sangue
Lipídeos/sangue
Masculino
Fenótipo
Prevalência
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipids)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


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[PMID]:28456681
[Au] Autor:Gallo A; Giral P; Carrié A; Carreau V; Béliard S; Bittar R; Maranghi M; Arca M; Cluzel P; Redheuil A; Bruckert E; Rosenbaum D
[Ad] Endereço:Unité de Prévention Cardiovasculaire, Service d'Endocrinologie-Métabolisme, Assistance Publique/Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière - Université Pierre et Marie Curie, Paris, France; Sorbonne Universités, UPMC Université Paris 06, INSERM 1146, CNRS 7371, Laboratoire d'imagerie Bi
[Ti] Título:Early coronary calcifications are related to cholesterol burden in heterozygous familial hypercholesterolemia.
[So] Source:J Clin Lipidol;11(3):704-711.e2, 2017 May - Jun.
[Is] ISSN:1933-2874
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The identification of high-risk patients with heterozygous familial hypercholesterolemia (HeFH) that may benefit from early treatment is challenging. Coronary Artery Calcification (CAC) score accounts for coronary atherosclerotic burden. It has proven its accuracy in cardiovascular risk assessment in the general population but data in HeFH are lacking. OBJECTIVE: The aim of our study was to assess CAC prevalence and its relationship with lifelong cholesterol exposure, calculated by total cholesterol burden (TCB) in patients with HeFH. METHODS: A total of 112 HeFH patients (50% males, median age 45 years) regularly followed-up since diagnosis were prospectively recruited at Pitié-Salpêtrière Hospital, Paris, France. CAC score was assessed using noncontrast multi-detector computed tomography. TCB was calculated as total cholesterol (TC) × age at diagnosis plus annually assessed TC. RESULTS: The prevalence of CAC was 58%. Patients without CAC showed lower TCB than patients with CAC (298 ± 110 vs 417.9 ± 89 mmol-years/L, P < .001). Among patients aged <45 years (n = 56), 39% exhibited CAC and a higher TCB compared with patients without CAC (352 ± 71 vs 255 ± 88 mmol-years/L, P < .001) due to higher TC levels at diagnosis (10.2 ± 2 vs 8.7 ± 2 mmol/L, P = .01). Multivariate analysis indicated that TCB was independently associated to CAC. CONCLUSIONS: Asymptomatic HeFH subjects exhibit early coronary atherosclerosis directly associated with TCB burden. CAC score may be useful to identify higher risk HeFH patients who can benefit from earlier and more aggressive treatment.
[Mh] Termos MeSH primário: Calcinose/complicações
Colesterol/metabolismo
Doença da Artéria Coronariana/complicações
Heterozigoto
Hiperlipoproteinemia Tipo II/complicações
Hiperlipoproteinemia Tipo II/metabolismo
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Hiperlipoproteinemia Tipo II/genética
Masculino
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
97C5T2UQ7J (Cholesterol)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


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[PMID]:28459663
[Au] Autor:Eslami SM; Nikfar S; Ghasemi M; Abdollahi M
[Ad] Endereço:Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
[Ti] Título:Does Evolocumab, as a PCSK9 Inhibitor, Ameliorate the Lipid Profile in Familial Hypercholesterolemia Patients? A Meta-Analysis of Randomized Controlled Trials.
[So] Source:J Pharm Pharm Sci;20:81-96, 2017.
[Is] ISSN:1482-1826
[Cp] País de publicação:Canada
[La] Idioma:eng
[Ab] Resumo:Proprotein convertase subtilisin-kexin type 9 (PCSK9) is a member of regulatory serine proteases which is mostly expressed in liver. In the physiological condition, LDL-C binds to LDL receptors (LDLRs) and via endocytosis, LDLRs are degraded. PCSK9 binds to the epidermal growth factor-like repeat A (EGFA) domain of extracellular LDLRs, and then physiological recycling of LDLRs from surface of liver is cancelled, resulting in elevation of circulating LDL-C in plasma. To evaluate whether evolucomab, as PCSK9 inhibitor monoclonal antibody, ameliorates lipid profile in familial hypercholesterolemia (FH) patients, this meta-analysis has been conducted. PubMed, Web of Science (ISI) and Scopus databases were searched for studies which had investigated the efficacy of evolucomab. Types of outcome investigated were percentage changes from baseline of the lipid profile. Our meta-analysis shows that evolucomab at the dosage of 420 mg monthly could decrease LDL-C  by 54.71%, TC by 35.08%, VLDL-C by 28.37 %, ratio of TC to HDL-C by 39.14 %, triglycerides by 12.11 %, and increased HDL-C by 6.06% from baseline compared to placebo at the end of study in FH patients. Our findings indicate that evolocumab could be a hopeful agent for challenging patients, such as statin intolerance or patients who fail to attain the target goal of LDL-C despite consumption of maximum doses of statins. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/farmacologia
HDL-Colesterol/antagonistas & inibidores
LDL-Colesterol/antagonistas & inibidores
Hiperlipoproteinemia Tipo II/tratamento farmacológico
Pró-Proteína Convertase 9/antagonistas & inibidores
Inibidores de Serino Proteinase/farmacologia
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/química
HDL-Colesterol/química
HDL-Colesterol/metabolismo
LDL-Colesterol/química
LDL-Colesterol/metabolismo
Relação Dose-Resposta a Droga
Seres Humanos
Hiperlipoproteinemia Tipo II/metabolismo
Modelos Moleculares
Pró-Proteína Convertase 9/metabolismo
Ensaios Clínicos Controlados Aleatórios como Assunto
Inibidores de Serino Proteinase/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 0 (Serine Proteinase Inhibitors); EC 3.4.21.- (PCSK9 protein, human); EC 3.4.21.- (Proprotein Convertase 9); LKC0U3A8NJ (evolocumab)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171222
[Lr] Data última revisão:
171222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.18433/J36C8N



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