Seminars in vascular medicine最新文献_第8页

Homozygous familial hypercholesterolemia and its management. 纯合子家族性高胆固醇血症及其管理。

Seminars in vascular medicine Pub Date : 2004-02-01 DOI: 10.1055/s-2004-822985

Adrian David Marais, Jean Catherine Firth, Dirk Jacobus Blom

{"title":"Homozygous familial hypercholesterolemia and its management.","authors":"Adrian David Marais, Jean Catherine Firth, Dirk Jacobus Blom","doi":"10.1055/s-2004-822985","DOIUrl":"https://doi.org/10.1055/s-2004-822985","url":null,"abstract":"Mutations in the low-density lipoprotein (LDL) receptor gene cause familial hypercholesterolemia. In homozygous familial hypercholesterolemia, both genes for the LDL- receptor are mutated and LDL levels are markedly elevated. High-density lipoprotein cholesterol concentration is often reduced and lipoprotein(a) levels are high when corrected for apolipoprotein(a) isoforms. Cutaneous and tendinous xanthomata develop in childhood and are the most common reason for initial presentation. The diagnosis can be confirmed by analysis of LDL-receptor genes or studies of LDL receptor function in cultured cells. Severe aortic and coronary atherosclerosis usually occurs within the first or second decades of life. Left ventricular outflow tract obstruction may be at the level of the aortic valve or the supravalvar aorta. Treatment for the hyperlipidemia is with plasmapheresis, high-dose statins, and ezetimibe. Liver transplantation reverses the metabolic defect but requires chronic immunosupression, and rejection may still occur. Liver transplantation is indicated if cardiac transplantation becomes necessary. Portocaval shunt may still play a role in patients with coronary artery disease who do not have access to plasmapheresis. Gene therapy is currently not practicable but is being actively developed.","PeriodicalId":87139,"journal":{"name":"Seminars in vascular medicine","volume":"4 1","pages":"43-50"},"PeriodicalIF":0.0,"publicationDate":"2004-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-2004-822985","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24568628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 59

Low-density lipoprotein receptor--its structure, function, and mutations. 低密度脂蛋白受体的结构、功能和突变。

Seminars in vascular medicine Pub Date : 2004-02-01 DOI: 10.1055/s-2004-822993

Joep C Defesche

{"title":"Low-density lipoprotein receptor--its structure, function, and mutations.","authors":"Joep C Defesche","doi":"10.1055/s-2004-822993","DOIUrl":"https://doi.org/10.1055/s-2004-822993","url":null,"abstract":"Uptake of cholesterol, mediated by the low-density lipoprotein (LDL)-receptor, plays a crucial role in lipoprotein metabolism. The LDL-receptor is responsible for the binding and subsequent cellular uptake of apolipoprotein B- and E-containing lipoproteins. To accomplish this, the receptor has to be transported from the site of synthesis, the membranes of the rough endoplasmatic reticulum (ER), through the Golgi apparatus, to its position on the surface of the cellular membrane. The translation of LDL-receptor messenger RNA into the polypeptide chain for the receptor protein takes place on the surface-bound ribosomes of the rough ER. Immature O-linked carbohydrate chains are attached to this integral precursor membrane protein. The molecular weight of the receptor at this stage is 120.000 d. The precursor-protein is transported from the rough ER to the Golgi apparatus, where the O-linked sugar chains are elongated until their final size is reached. The molecular weight has then increased to 160.000 d. The mature LDL-receptor is subsequently guided to the \"coated pits\" on the cell surface. These specialized areas of the cell membrane are rich in clathrin and interact with the LDL-receptor protein. Only here can the LDL-receptor bind LDL-particles. Within 3 to 5 minutes of its formation, the LDL-particle-receptor complex is internalized through endocytosis and is further metabolized through the receptor-mediated endocytosis pathway. Mutations in the gene coding for the LDL-receptor can interfere to a varying extent with all the different stages of the posttranslational processing, binding, uptake, and subsequent dissociation of the LDL-particle-LDL-receptor complex, but invariably the mutations lead to familial hypercholesterolemia. Thus, mutations in the LDL-receptor gene give rise to a substantially varying clinical expression of familial hypercholesterolemia.","PeriodicalId":87139,"journal":{"name":"Seminars in vascular medicine","volume":"4 1","pages":"5-11"},"PeriodicalIF":0.0,"publicationDate":"2004-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-2004-822993","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24569364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 62

Review Questions 审查问题

Seminars in vascular medicine Pub Date : 2004-02-01 DOI: 10.1055/s-2004-832707

引用次数: 0

Laboratory-based assessment of plasma lipids and lipoproteins for the classification of familial hypercholesterolemic and hypertriglyceridemic states. 家族性高胆固醇血症和高甘油三酯血症状态的血脂和脂蛋白分类的实验室评估。

Seminars in vascular medicine Pub Date : 2004-02-01 DOI: 10.1055/s-2004-822982

Pierre N M Demacker

引用次数: 1

Cost-effectiveness analysis of the genetic screening program for familial hypercholesterolemia in The Netherlands. 荷兰家族性高胆固醇血症基因筛查项目的成本-效果分析。

Seminars in vascular medicine Pub Date : 2004-02-01 DOI: 10.1055/s-2004-822992

David Wonderling, Marina A W Umans-Eckenhausen, Dalya Marks, Joep C Defesche, John J P Kastelein, Margaret Thorogood

{"title":"Cost-effectiveness analysis of the genetic screening program for familial hypercholesterolemia in The Netherlands.","authors":"David Wonderling, Marina A W Umans-Eckenhausen, Dalya Marks, Joep C Defesche, John J P Kastelein, Margaret Thorogood","doi":"10.1055/s-2004-822992","DOIUrl":"https://doi.org/10.1055/s-2004-822992","url":null,"abstract":"Familial hypercholesterolemia (FH) is associated with pronounced atherosclerosis leading to premature cardiovascular disease and untimely death. Despite the availability of effective preventative drug treatments, many affected individuals remain undiagnosed and untreated until they become symptomatic with cardiovascular disease. To assess the cost-effectiveness of systematic genetic screening of family members of persons diagnosed with FH, an analysis was conducted using data from a nationwide screening program for the identification of individuals with FH, instituted in The Netherlands in 1994, and from other sources. There was DNA testing of families with a known genetic defect to identify new cases of FH in the presymptomatic stage of the disease. After identification, most newly identified patients were started on cholesterol-lowering statin treatment. On average, new cases diagnosed by the screening program gained 3.3 years of life each. Twenty-six myocardial infarctions would be avoided for every 100 persons treated with statins between the ages of 18 and 60 years. The average total lifetime incremental costs, over all age ranges and both sexes, including costs for screening and testing, lifetime drug treatment, and treatment of cardiovascular events, was US dollars 7500 per new case identified. Cost per life-year gained was US dollars 8700. Therefore, systematic genetic screening of family members of persons diagnosed with FH is cost-effective in The Netherlands and should be considered for other settings.","PeriodicalId":87139,"journal":{"name":"Seminars in vascular medicine","volume":"4 1","pages":"97-104"},"PeriodicalIF":0.0,"publicationDate":"2004-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-2004-822992","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24568505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 139

Clinical, diagnostic, and therapeutic aspects of familial hypercholesterolemia. 家族性高胆固醇血症的临床、诊断和治疗方面。

Seminars in vascular medicine Pub Date : 2004-02-01 DOI: 10.1055/s-2004-822984

Emily S van Aalst-Cohen, Angelique C M Jansen, Saskia de Jongh, Pernette R W de Sauvage Nolting, John J P Kastelein

{"title":"Clinical, diagnostic, and therapeutic aspects of familial hypercholesterolemia.","authors":"Emily S van Aalst-Cohen, Angelique C M Jansen, Saskia de Jongh, Pernette R W de Sauvage Nolting, John J P Kastelein","doi":"10.1055/s-2004-822984","DOIUrl":"https://doi.org/10.1055/s-2004-822984","url":null,"abstract":"Heterozygous familial hypercholesterolemia (FH) is a common inherited disorder of lipoprotein metabolism. FH is characterized by elevated levels of low-density lipoprotein cholesterol, the presence of tendon xanthomas, and premature cardiovascular disease. The underlying molecular defect of FH consists of mutations in the gene coding for the low-density-lipoprotein-receptor protein, detection of which provides the only unequivocal diagnosis. Although the cause of FH is monogenic, there is wide variation in the onset and severity of atherosclerotic disease in these patients. Additional atherogenic risk factors of environmental, metabolic, and genetic origin are presumed to influence the clinical phenotype in FH. Criteria used to identify individuals with FH include a combination of clinical characteristics, personal and family history of early coronary artery disease, and biochemical parameters. Since the introduction in 1989 of statins, which have been shown to be effective and to delay or prevent the onset of cardiovascular disease, drug treatment of FH has greatly improved. New lipid-lowering agents are presently being developed for clinical use. This review provides an update on the clinical, diagnostic, and therapeutic aspects of heterozygous familial hypercholesterolemia.","PeriodicalId":87139,"journal":{"name":"Seminars in vascular medicine","volume":"4 1","pages":"31-41"},"PeriodicalIF":0.0,"publicationDate":"2004-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-2004-822984","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24568627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 58

Assessment of risk factors for coronary heart disease in vascular medicine: long-term experience and a personal view from the laboratory. 血管医学中冠心病危险因素的评估:长期经验和实验室个人观点。

Seminars in vascular medicine Pub Date : 2004-02-01 DOI: 10.1055/s-2004-822983

Pierre N M Demacker

{"title":"Assessment of risk factors for coronary heart disease in vascular medicine: long-term experience and a personal view from the laboratory.","authors":"Pierre N M Demacker","doi":"10.1055/s-2004-822983","DOIUrl":"https://doi.org/10.1055/s-2004-822983","url":null,"abstract":"Physicians should be properly informed of the clinical chemistry diagnostic potential for the diagnosis and classification of hyper- and dyslipidemias by laboratory determinations of lipids, lipoproteins, and apolipoproteins. New analytes are regularly found to be relevant for screening and risk estimation for coronary artery disease in vascular medicine. These analytes can be distinguished between parameters working on the long-term or working acutely. However, in times of restricted laboratory budgets, it is not always possible to add the new analyte to the routine diagnostic supply without having answered the question of whether the new analyte indeed adds to the chronic or acute risk estimation power presently available. This is relevant for homocysteine and for C-reactive protein (CRP). Both parameters appear to be interrelated to most common cardiovascular risk factors supposed to promote atherosclerosis and to ultimately provoke cardiovascular disease, and in fact are not independent. The latter certainly has added value in acute situations. With regard to the chronic risk estimators, it must be concluded that there is a multifactorial influence, with an important contribution made by social and lifestyle factors. This review draws attention to the multifactorial aspects of coronary heart disease, risk profiling using computer programs, socioeconomic factors, and implementation problems of interventions.","PeriodicalId":87139,"journal":{"name":"Seminars in vascular medicine","volume":"4 1","pages":"23-9"},"PeriodicalIF":0.0,"publicationDate":"2004-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-2004-822983","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24569368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Familial hypercholesterolemia in South Africa. 南非家族性高胆固醇血症。

Seminars in vascular medicine Pub Date : 2004-02-01 DOI: 10.1055/s-2004-822991

Adrian David Marais, Jean Catherine Firth, Dirk Jacobus Blom

引用次数: 9

Advanced method for the identification of patients with inherited hypercholesterolemia. 遗传性高胆固醇血症患者的先进鉴别方法。

Seminars in vascular medicine Pub Date : 2004-02-01 DOI: 10.1055/s-2004-822987

Joep C Defesche, Peter J Lansberg, Marina A W Umans-Eckenhausen, John J P Kastelein

{"title":"Advanced method for the identification of patients with inherited hypercholesterolemia.","authors":"Joep C Defesche, Peter J Lansberg, Marina A W Umans-Eckenhausen, John J P Kastelein","doi":"10.1055/s-2004-822987","DOIUrl":"https://doi.org/10.1055/s-2004-822987","url":null,"abstract":"Familial hypercholesterolemia (FH) has a prevalence of 1 in 500 in Western society and predisposes for premature cardiovascular disease. Lipid-lowering treatment of affected individuals is widely advocated. Maximum health beneﬁt can be obtained in FH if treatment is started as early as possible, as the World Health Organization has recently recommended. In 1994 we initiated an active case-ﬁnding program for individuals with FH, based on family investigation and DNA-testing. In an initial pilot study we established that active family screening supported by DNA diagnostics resulted in the identiﬁcation of substantial numbers of FH heterozygotes and determined that diagnosis by DNA analysis was superior to conventional cholesterol measurement. Since its initiation, the program has led to the identiﬁcation of more than 6000 individuals with FH, of whom the greatest part was not adequately treated at the time of identiﬁcation. Our ﬁndings indicate not only that this case-ﬁnding approach is effective in identifying FH patients who otherwise would not have been identiﬁed but also that the vast majority of these patients seek treatment and are successfully started on cholesterol-lowering therapy to reduce their risk of premature cardiovascular disease. Here we describe an effective model to identify and bring under treatment large numbers of individuals affected by FH.","PeriodicalId":87139,"journal":{"name":"Seminars in vascular medicine","volume":"4 1","pages":"59-65"},"PeriodicalIF":0.0,"publicationDate":"2004-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-2004-822987","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24568631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Antiplatelet agents in acute coronary syndromes. 急性冠状动脉综合征中的抗血小板药物。

Seminars in vascular medicine Pub Date : 2003-11-01 DOI: 10.1055/s-2004-817689

John W Eikelboom, Sonia Anand

引用次数: 2