Clinical Research in Cardiology Supplements最新文献

Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels. 脂蛋白分离是降低增高的Lp(a)水平的最佳治疗选择。

Clinical Research in Cardiology Supplements Pub Date : 2019-04-01 DOI: 10.1007/s11789-019-00094-4

V J J Schettler, C L Neumann, C Peter, T Zimmermann, U Julius, B Hohenstein, E Roeseler, F Heigl, P Grützmacher, H Blume, R Klingel, A Vogt

{"title":"Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels.","authors":"V J J Schettler, C L Neumann, C Peter, T Zimmermann, U Julius, B Hohenstein, E Roeseler, F Heigl, P Grützmacher, H Blume, R Klingel, A Vogt","doi":"10.1007/s11789-019-00094-4","DOIUrl":"https://doi.org/10.1007/s11789-019-00094-4","url":null,"abstract":"Background: Lipoprotein(a) (Lp(a)) is a genetic risk factor for cardiovascular disease (CVD) and is associated with the induction and sustaining of atherosclerotic cardiovascular diseases (ASCVD). Since 2008 Lp(a) along with progressive CVD has been approved as an indication for regular lipoprotein apheresis (LA) in Germany. The German Lipoprotein Apheresis Registry (GLAR) has been initiated to provide statistical evidence for the assessment of extracorporeal procedures to treat dyslipidemia for both LDL-cholesterol (LDL-C) and Lp(a). The GLAR now allows prospective investigations over a 5-year period about annual incidence rates of cardiovascular events. Here Lp(a) patients (LDL-C < 100 mg/dl; Lp(a) > 60 mg/dl or >120 nmol/l) showed the same reduction of major coronary (83%) and non-coronary events (63%) as had been formerly shown in the Pro(a)LiFe study. However, Lp(a) is not only an apolipoprotein(a) (apo(a)) and LDL-C containing particle, which is covalently bound to a LDL-C core by a disulphide bridge. The composition of this particle, inter alia containing oxidized phospholipids, gives pro-atherosclerotic, pro-inflammatory, and pro-thrombotic properties, inducing atherosclerotic processes mainly in the arterial wall. However, recent investigations have shown that a reduction of inflammatory settings without LDL-C or Lp(a) reduction may reduce ASCVD events. Lipoprotein apheresis (LA) could not only reduce LDL-C and Lp(a) in parallel, but also different inflammatory and coagulation parameters. In summary lipoprotein apheresis is not only anti-atherosclerotic, but also anti-inflammatory and anti-thrombotic and therefore an ideal treatment option with respect to the shown reduction of major adverse coronary events (MACE) and major adverse non-coronary events (MANCE) by reducing Lp(a) levels.","PeriodicalId":39208,"journal":{"name":"Clinical Research in Cardiology Supplements","volume":"14 Suppl 1","pages":"33-38"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11789-019-00094-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37027043","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: 22

Lipoprotein(a) and mortality-a high risk relationship. 脂蛋白(a)与死亡率-高危险关系。

Clinical Research in Cardiology Supplements Pub Date : 2019-04-01 DOI: 10.1007/s11789-019-00095-3

Reinhard Klingel, Andreas Heibges, Cordula Fassbender

{"title":"Lipoprotein(a) and mortality-a high risk relationship.","authors":"Reinhard Klingel, Andreas Heibges, Cordula Fassbender","doi":"10.1007/s11789-019-00095-3","DOIUrl":"https://doi.org/10.1007/s11789-019-00095-3","url":null,"abstract":"Lipoprotein(a) (Lp(a)) is an independent cardiovascular risk factor playing a causal role for atherosclerotic cardiovascular disease (ASCVD). Early or progressive ASCVD or a familial predisposition are key findings which can be associated with Lp(a)-hyperlipoproteinemia (Lp(a)-HLP). The German guideline for the indication of lipoprotein apheresis in patients with Lp(a)-HLP has proved to be of value to identify patients at highest risk, using the composite of a Lp(a) threshold >60 mg/dl (>120 nmol/l) and clinical ASCVD progression despite effective LDL-C lowering therapy. In particular for such patients it appears to be plausible that Lp(a)-associated risk would increase cardiovascular mortality as the most important part of total mortality in Western populations. By the majority of existing investigations an association of Lp(a) concentration on total or cardiovascular mortality was demonstrated. However, inconsistency in the findings between studies exists without a clear trend for any study feature to explain this. Genetic homogeneity of the population, long-term follow-up, and clinically guided selection of patients might be important to further clarify the impact of Lp(a) concentration on progression of ASCVD, and finally total or cardiovascular mortality. LDL and Lp(a) particles exhibit a mutual effect modification on related ASCVD risk. Therefore, LDL-C levels and concomitant LDL-C lowering treatment must be considered in this context. Prospective evaluation is needed to document that specific Lp(a)-lowering additional to targeted LDL-C lowering will in fact reduce cardiovascular or total mortality.","PeriodicalId":39208,"journal":{"name":"Clinical Research in Cardiology Supplements","volume":"14 Suppl 1","pages":"13-19"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11789-019-00095-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37027045","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: 7

Lipoprotein(a)-antisense therapy. 脂蛋白(a)反义疗法。

Clinical Research in Cardiology Supplements Pub Date : 2019-04-01 DOI: 10.1007/s11789-019-00096-2

Anja Vogt

{"title":"Lipoprotein(a)-antisense therapy.","authors":"Anja Vogt","doi":"10.1007/s11789-019-00096-2","DOIUrl":"https://doi.org/10.1007/s11789-019-00096-2","url":null,"abstract":"Elevated levels of lipoprotein(a) (Lp(a)) contribute to the risk of early and severe cardiovascular disease (CVD) and Lp(a) is acknowledged as a risk factor to be included in risk assessment. The established lipid-modifying medical therapies do not lower Lp(a) except niacin but no data of endpoint trials are available. Of the new lipid-modifying drugs a few have some impact on Lp(a). Whether the Lp(a) lowering effect contributes to the reduction of CVD events would have to be shown in Lp(a) dedicated trials. None of the available agents is indicated to lower Lp(a). Lipoprotein apheresis lowers levels of Lp(a) significantly by >60% per treatment. Trial data and data of the German Lipoprotein Apheresis Registry show that regular apheresis reduces cardiovascular events. The Apo(a) antisense oligonucleotide is the only approach to specifically lower Lp(a). The IONIS-APO(a)Rx phase 1 and 2 trials showed very substantial decreases of Lp(a) and good tolerability. The hepatospecific variant IONIS-APO(a)-LRx is 30 times more potent. The results of the IONIS-APO(a)-LRx phase 2 trial were presented recently. The highest dosages reduced Lp(a) by 72 and 80%; in about 81 and 98% Lp(a) levels <50 mg/dl were achieved. Tolerability and safety were confirmed, whereby injection site reactions were the most common side effects. This raises hope that the planned phase 3 trial will reproduce these findings and show a reduction of cardiovascular events.","PeriodicalId":39208,"journal":{"name":"Clinical Research in Cardiology Supplements","volume":"14 Suppl 1","pages":"51-56"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11789-019-00096-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37045138","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: 9

Lipoprotein(a). 脂蛋白(a)。

Clinical Research in Cardiology Supplements Pub Date : 2019-04-01 DOI: 10.1007/s11789-019-00100-9

K P Mellwig, A Vogt

引用次数: 1

Prediction of cardiovascular risk by Lp(a) concentrations or genetic variants within the LPA gene region. 通过Lp(a)浓度或LPA基因区域的遗传变异预测心血管风险。

Clinical Research in Cardiology Supplements Pub Date : 2019-04-01 DOI: 10.1007/s11789-019-00093-5

Florian Kronenberg

引用次数: 27

Lipoprotein(a) apheresis in patients with peripheral arterial disease: rationale and clinical results. 外周动脉疾病患者的脂蛋白(a)单采:基本原理和临床结果

Clinical Research in Cardiology Supplements Pub Date : 2019-04-01 DOI: 10.1007/s11789-019-00097-1

Norbert Weiss, Ulrich Julius

{"title":"Lipoprotein(a) apheresis in patients with peripheral arterial disease: rationale and clinical results.","authors":"Norbert Weiss, Ulrich Julius","doi":"10.1007/s11789-019-00097-1","DOIUrl":"https://doi.org/10.1007/s11789-019-00097-1","url":null,"abstract":"Patients with symptomatic peripheral arterial disease (PAD) are at a very high risk of cardiovascular morbidity and mortality. Elevated lipoprotein(a) levels have been shown to be a risk factor for coronary artery disease (CAD) and stroke. More recently elevated lipoprotein(a) levels have also been demonstrated to be associated with prevalent and incident PAD, and even may be a stronger risk factor for PAD compared with CAD. Lipoprotein apheresis is currently the only efficient way to lower lipoprotein(a) levels. Lipoprotein(a) apheresis has been shown to reduce major coronary events in patients with CAD. There is increasing evidence that lipoprotein(a) apheresis also reduces the rate of major adverse limb events such as peripheral revascularizations and amputations in PAD patients, and improves symptoms of PAD such as pain on exertion. This review summarizes the current knowledge on the clinical role of lipoprotein(a) for PAD and the disease-specific effect of lipoprotein(a) apheresis, and suggests indications for screening for and treating of elevated lipoprotein(a) levels in patients with PAD.","PeriodicalId":39208,"journal":{"name":"Clinical Research in Cardiology Supplements","volume":"14 Suppl 1","pages":"39-44"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11789-019-00097-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37058942","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: 9

Lipoprotein(a) and proprotein convertase subtilisin/kexin type 9 inhibitors. 脂蛋白(a)和蛋白转化酶枯草杆菌素/kexin 9型抑制剂。

Clinical Research in Cardiology Supplements Pub Date : 2019-04-01 DOI: 10.1007/s11789-019-00099-z

U Julius, S Tselmin, U Schatz, S Fischer, S R Bornstein

{"title":"Lipoprotein(a) and proprotein convertase subtilisin/kexin type 9 inhibitors.","authors":"U Julius, S Tselmin, U Schatz, S Fischer, S R Bornstein","doi":"10.1007/s11789-019-00099-z","DOIUrl":"https://doi.org/10.1007/s11789-019-00099-z","url":null,"abstract":"Lipoprotein(a) (Lp(a)) is an internationally accepted independent atherogenic risk factor. Details about its synthesis, many aspects of composition and clearance from the bloodstream are still unknown. LDL receptor (LDLR) (and probably other receptors) play a role in the elimination of Lp(a) particles. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors increase the number of available LDLRs and in this way very effectively reduce the LDL cholesterol (LDL-C) concentrations. As shown in controlled studies using PCSK9 inhibitors, Lp(a) levels are decreased by 20 to 30%, though in some patients no effect was observed. So far, it has not been clarified whether this decrease is associated with an effect on the incidence of cardiovascular events (CVEs). In two recently published well-performed secondary prevention studies (FOURIER with evolocumab, ODYSSEY OUTCOMES with alirocumab) baseline Lp(a) levels were shown to have an impact on CVEs independently of baseline LDL-C concentrations. The rather modest PCSK9 inhibitor-induced decrease of Lp(a) was associated with a reduction of CVEs in both studies, even after adjusting (ODYSSEY OUTCOMES) for demographic variables (age, sex, race, region), baseline Lp(a), baseline LDL-C, change in LDL-C, and clinical variables (time from acute coronary syndrome, body mass index, diabetes, smoking history). The largest decrease of CVEs was seen in patients with relatively low concentrations of both LDL-C and Lp(a) (FOURIER). These findings will probably have an influence on the use of PCSK9 inhibitors in patients with high Lp(a) concentrations.","PeriodicalId":39208,"journal":{"name":"Clinical Research in Cardiology Supplements","volume":"14 Suppl 1","pages":"45-50"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11789-019-00099-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37027046","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: 11

Lipoprotein(a)-an interdisciplinary challenge. 脂蛋白(a)——一个跨学科的挑战。

Clinical Research in Cardiology Supplements Pub Date : 2019-04-01 DOI: 10.1007/s11789-019-00098-0

U Julius, S Tselmin, U Schatz, S Fischer, S R Bornstein

{"title":"Lipoprotein(a)-an interdisciplinary challenge.","authors":"U Julius, S Tselmin, U Schatz, S Fischer, S R Bornstein","doi":"10.1007/s11789-019-00098-0","DOIUrl":"https://doi.org/10.1007/s11789-019-00098-0","url":null,"abstract":"Lipoprotein(a) (Lp(a)) is an internationally recognized atherogenic risk factor which is inherited and not changed by nutrition or physical activity. At present, only proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may modestly decrease its concentration (but not in all patients)-leading to a certain decrease in cardiovascular events (CVE) in controlled studies. However, at present an elevation of Lp(a) is not a generally accepted indication for their use. More effective is lipoprotein apheresis (LA) therapy with respect to both lowering Lp(a) levels and reduction of CVE. In the future, an antisense oligonucleotide against apolipoprotein(a) will probably be available. Atherosclerosis in patients with an elevation of Lp(a) may affect several vessel regions (carotids, aorta, coronaries, leg arteries). Thus, Lp(a) should be measured in high-risk patients. These patients are usually cared for by their family doctors and by other specialists who should closely cooperate. Lipidologists should decide whether costly therapies like PCSK9 inhibitors or LA should be started. The main aim of current therapy is to optimize all other risk factors (LDL cholesterol, hypertension, diabetes mellitus, body weight, renal insufficiency). Patients should be regularly monitored (lab data, heart, arteries). This paper describes the duties of physicians of different specialties when caring for patients with high Lp(a) concentrations.","PeriodicalId":39208,"journal":{"name":"Clinical Research in Cardiology Supplements","volume":"14 Suppl 1","pages":"20-27"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11789-019-00098-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37027981","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

Is lipoprotein(a) a risk factor for ischemic stroke and venous thromboembolism? 脂蛋白(a)是缺血性卒中和静脉血栓栓塞的危险因素吗?

Clinical Research in Cardiology Supplements Pub Date : 2019-04-01 DOI: 10.1007/s11789-019-00101-8

Alexander Heinrich Nave, Arnold von Eckardstein

{"title":"Is lipoprotein(a) a risk factor for ischemic stroke and venous thromboembolism?","authors":"Alexander Heinrich Nave, Arnold von Eckardstein","doi":"10.1007/s11789-019-00101-8","DOIUrl":"https://doi.org/10.1007/s11789-019-00101-8","url":null,"abstract":"The structural similarity with plasminogen as well as thrombogenic and atherogenic in vitro functions raise the question if lipoprotein(a) (Lp(a)) is a risk factor for venous thromboembolism (VTE) and ischemic stroke. Numerous case-control and prospective studies using different cut-off values to define high Lp(a) generated conflicting evidence for both VTE and ischemic stroke. Several meta-analyses demonstrated independent associations of elevated Lp(a) with a history of VTE or ischemic stroke. However, the evidence of prospective studies for associations of Lp(a) with incident stroke or recurrent VTE remains inconclusive. For ischemic stroke, data suggest that Lp(a) increases the risk of large-artery atherosclerosis stroke, but not cardioembolic or lacunar stroke. Lp(a) may increase the risk of VTE in the presence of additional thrombophilic risk factors. Larger cohort studies are needed to elaborate the importance of higher Lp(a) cut-offs and interactions with other risk factors and subgroups of stroke or VTE. The value of Lp(a) to estimate residual vascular risk after the first thromboembolic event remains to be adequately explored.","PeriodicalId":39208,"journal":{"name":"Clinical Research in Cardiology Supplements","volume":"14 Suppl 1","pages":"28-32"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11789-019-00101-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37027044","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: 7

Erratum to: The German Lipoprotein Apheresis Registry (GLAR) - almost 5 years on. 勘误：德国脂蛋白分离注册（GLAR）--近 5 年来。

Clinical Research in Cardiology Supplements Pub Date : 2017-07-17 DOI: 10.1007/s11789-017-0092-1

V J J Schettler, C L Neumann, C Peter, T Zimmermann, U Julius, E Roeseler, F Heigl, P Grützmacher, H Blume, A Vogt

引用次数: 0