scholarly journals LDL-Apheresis: Technical and Clinical Aspects

2012 ◽  
Vol 2012 ◽  
pp. 1-19 ◽  
Author(s):  
Rolf Bambauer ◽  
Carolin Bambauer ◽  
Boris Lehmann ◽  
Reinhard Latza ◽  
Ralf Schiel
Keyword(s):  
Therapeutic Option ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Clinical Aspects ◽  
Published Data ◽  
Ldl Apheresis ◽  
Lipoprotein A ◽  
Regular Treatment ◽  
Lipid Lowering Drugs

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) levels, and coronary heart disease refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are five different LDL-apheresis systems available: cascade filtration or lipid filtration, immunoadsorption, heparin-induced LDL precipitation, dextran sulfate LDL adsorption, and the LDL hemoperfusion. There is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, sometimes the goal of therapy cannot be reached. Hence, in such patients, treatment with LDL-apheresis is indicated. Technical and clinical aspects of these five different LDL-apheresis methods are shown here. There were no significant differences with respect to or concerning all cholesterols, or triglycerides observed. With respect to elevated lipoprotein (a) levels, however, the immunoadsorption method seems to be most effective. The different published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.

Lipoprotein(a): when to measure, how to treat?

2015 ◽  
Vol 39 (2) ◽  
Author(s):  
Indumathi Chennamsetty ◽  
Hubert Scharnagl ◽  
Marcus E. Kleber ◽  
Winfried März ◽  
Gert M. Kostner
Keyword(s):  
Antisense Oligonucleotides ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
Lipid Lowering ◽  
Lipoprotein A ◽  
Causal Risk Factor ◽  
The Right ◽  
Genetically Determined ◽  
Binding Sequence

Abstract:Lipoprotein(a) [Lp(a)] is one of the most atherogenic lipoproteins consisting of a core low-density lipoprotein particle and the specific glycoprotein apo(a). Apo(a) is homologous to plasminogen yet in contrast exhibits a specific size polymorphism. This polymorphism is due to the fact that the number of kringle-IV (K-IV) repeats ranges between two and approximately 50. Apo(a) is synthesized almost exclusively in the liver, and there is still some discussion regarding whether the assembly of Lp(a) occurs intracellularly or in the circulating blood. The plasma Lp(a) concentration is markedly skewed to the right and extends from <1 mg/dL to more than 200 mg/dL. Up to 90% of the variance of Lp(a) concentrations may be genetically determined and the Lp(a) concentration correlates inversely with the number of K-IV repeats. In the apo(a) promoter there are numerous response elements for transcription factors and nuclear receptors, whereby the HNF4α binding sequence is the most important one. Activation of FXR causes the dissociation of HNF4α from its response element and in turn a significant down regulation of apo(a) transcription. Recent large epidemiological studies document beyond any doubt that Lp(a) is an independent causal risk factor for coronary heart disease and myocardial infarction. Hence, novel approaches to correct elevated Lp(a) are under investigation. Among the established lipid-lowering drugs, only nicotinic acid lowers Lp(a) in a consistent and clinically relevant fashion, and we recently elucidated the molecular mechanism underlying this effect. Novel medicines in clinical trials include CETP inhibitors, PCSK9 antibodies, the MTP inhibitor lomitapide and antisense oligonucleotides. APO(a)

Effects of serum lipoproteins on cyclosporine A cellular uptake and renal toxicity in vitro

2014 ◽  
Vol 92 (2) ◽  
pp. 140-148 ◽  
Author(s):  
Dion R. Brocks ◽  
Hetal R. Chaudhary ◽  
Mohamed Ben-Eltriki ◽  
Marwa E. Elsherbiny ◽  
Ayman O.S. El-Kadi
Keyword(s):  
Cellular Uptake ◽  
Cyclosporine A ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Serum Lipoproteins ◽  
Rat Serum ◽  
Lipid Lowering Drugs ◽  
Density Lipoprotein Receptor

In-vitro studies were performed to shed light on previous findings that showed increased uptake of cyclosporine A in the kidneys and liver of hyperlipidemic rats, and increased signs of kidney toxicity. Hepatocytes were obtained from rats, cultured, and exposed to a diluted serum from hyperlipidemic rats. Some cells were also exposed to lipid-lowering drugs. After washing out the rat serum or lipid-lowering drugs, cells were exposed to cyclosporine A embedded in serum lipoproteins. Pretreatment with hyperlipidemic serum and lipid-lowering drugs was associated with an increased uptake of cyclosporine A. As expected, atorvastatin caused an increase in low density lipoprotein receptor and a decrease in MDR1A mRNA in the hepatocytes. A decrease in NRK-52E rat renal tubular cellular viability caused by cyclosporine A was noted when cells were preincubated with diluted hyperlipidemic serum. This was matched with evidence of hyperlipidemic-serum-associated increases in the NRK-52E cellular uptake of cyclosporine A and rhodamine-123. The findings of these experiments suggested that in hyperlipidemia the expression and (or) the functional activity of P-glycoprotein was diminished, leading to greater hepatic and renal uptake of cyclosporine A, and renal cellular toxicity.

scholarly journals An expert opinion paper on statin adherence and implementation of new lipid-lowering medications by the ESC Working Group on Cardiovascular Pharmacotherapy: Barriers to be overcome

2019 ◽  
Vol 6 (2) ◽  
pp. 115-121 ◽  
Author(s):  
Heinz Drexel ◽  
Andrew J S Coats ◽  
Ilaria Spoletini ◽  
Claudio Bilato ◽  
Vincenzo Mollace ◽  
...  
Keyword(s):  
Working Group ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Position Paper ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipid Lowering Drugs ◽  
Cardiovascular Pharmacotherapy ◽  
Statin Adherence

Abstract Benefits and safety on statins have been well-established over 20 years of research. Despite this, the vast majority of patients are not adequately treated and do not achieve the low-density lipoprotein cholesterol target levels. This is mainly due to poor adherence, which is associated with dangerous and sometimes fatal outcomes. To increase adherence and prevent worse outcomes, a combination therapy with lower dosage of statins and new lipid-lowering drugs may be used. However, the implementation of new lipid-lowering drugs in European countries is still at the beginning. For these reasons, the aim of this position paper is to give an up-to-date indication from the ESC Working Group on Cardiovascular Pharmacotherapy in order to discuss the barriers towards statins adherence and new lipid-lowering drugs implementation in Europe.

scholarly journals Role of Lipoprotein Apheresis in Cardiovascular Disease Risk Reduction

2019 ◽  
Vol 47 (4) ◽  
pp. 301-316 ◽  
Author(s):  
Rupesh Raina ◽  
Claire Young ◽  
Vinod Krishnappa ◽  
Rahul Chanchlani
Keyword(s):  
Cardiovascular Disease ◽  
Disease Risk ◽  
Therapeutic Option ◽  
Cardiovascular Disease Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Lipoprotein ◽  
Lipid Lowering ◽  
Lipoprotein Apheresis ◽  
Prevention Methods

Background and Aim: Elevated low-density lipoprotein cholesterol and/or lipoprotein(a) are established risk factors for cardiovascular disease (CVD). Management of hypercholesterolemia consists of drug therapies, including statins and proprotein convertase subtilisin/kexin type 9 inhibitors. In patients with familial hypercholesterolemia (FH), lipoprotein apheresis (LA) is utilized to control lipid levels. However, LA is not currently a standard therapy for non-FH. This review summarizes the literature regarding LA therapy in CVD prevention. Methods: PubMed/MEDLINE databases were searched using the keywords “LA” and “CVD”. Citations were individually reviewed for relevance. Results: The efficacy of LA was clearly demonstrated, largely based on evidence from observational studies. In patients who are unresponsive to traditional lipid-lowering medications, LA effectively reduced serum lipoprotein levels and adverse cardiovascular events. Conclusion: It was concluded that LA is a safe and effective technique that could be considered in the management of hypercholesterolemia and future risk. Randomized control trials would further support a role for LA as a therapeutic option.

Importance of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the treatment of dyslipidemia and atherosclerosis

2019 ◽  
pp. 40-52
Author(s):  
Maksim Maksimov ◽  
Anastasia Shikaleva ◽  
Aleksandra Kuchaeva
Keyword(s):  
Clinical Studies ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Pcsk9 Inhibitors ◽  
Lipid Lowering Drugs ◽  
Antibody Preparations

Representatives of different groups of lipid-lowering drugs may have some differences in the nature and severity of the effect on the blood lipid spectrum. A new class of drugs, PCSK9 inhibitors, whose activity is associated with a protein involved in the control of low density lipoprotein receptors, has recently appeared. In clinical practice, this group is represented by monoclonal antibody preparations evolocumab and alirocumab. PCSK9 inhibitors are promising drugs for use in combination lipid-lowering therapy, which so far, given the results of clinical studies, can be recommended in the third place after statins and ezetimibe. In clinical studies, it was shown that alirocoumab and evolocumab alone or in combination with statins and/or other lipid-lowering drugs significantly reduce cholesterol levels in low density lipoproteins – by an average of 60%, depending on the dose.

scholarly journals Influence of lipid-lowering drugs on inflammation: what is yet to be done?

2021 ◽  
Author(s):  
Sabina Ugovšek ◽  
Janja Zupan ◽  
Andreja Rehberger Likozar ◽  
Miran Sebestjen
Keyword(s):  
Cardiovascular Events ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
C Reactive Protein ◽  
Low Density Lipoprotein Cholesterol ◽  
Reactive Protein ◽  
Lipid Lowering Drugs

Atherosclerosis is a chronic inflammatory disease that is associated with risk of cardiovascular events. The best-characterised and well-standardised clinical indicator of inflammation is C-reactive protein. Current evidence-based drug therapies for prevention and treatment of cardiovascular diseases are mainly focused on reduction of low-density lipoprotein cholesterol. However, these drugs do not provide sufficient protection against recurrent cardiovascular events. One of the possible mechanisms behind this recurrence might be the persistence of residual inflammation. For the most commonly used lipid-lowering drugs, the statins, their reduction of cardiovascular events goes beyond lowering of low-density lipoprotein cholesterol. Here, we review the effects of these lipid-lowering drugs on inflammation, in terms of statins, ezetimibe, fibrates, niacin, proprotein convertase subtilisin/kexin type 9 inhibitors, bempedoic acid, ethyl eicosapentaenoic acid and antisense oligonucleotides. We focus in particular on C-reactive protein, and discuss how the effects of the statins might be related to reduced rates of cardiovascular events.

scholarly journals Lipoprotein(a)- and low-density lipoprotein–derived cholesterol in nephrotic syndrome: Impact on lipid-lowering therapy?

2004 ◽  
Vol 66 (1) ◽  
pp. 348-354 ◽  
Author(s):  
Florian Kronenberg ◽  
Arno Lingenhel ◽  
Karl Lhotta ◽  
Barbara Rantner ◽  
Martina F. Kronenberg ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Lipoprotein A ◽  
Lowering Therapy

Effects of Lipid Lowering Drugs on Arterial Stiffness: One More Way to Reduce Cardiovascular Risk?

2019 ◽  
Vol 18 (1) ◽  
pp. 38-42 ◽  
Author(s):  
Andromachi Reklou ◽  
Niki Katsiki ◽  
Asterios Karagiannis ◽  
Vasilios Athyros
Keyword(s):  
Arterial Stiffness ◽  
Beneficial Effect ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
High Dose ◽  
Pcsk9 Inhibitors ◽  
Vascular Events ◽  
Lipid Lowering Drugs ◽  
Meta Analyses

Arterial stiffness (AS) is considered an independent predictor of cardiovascular disease (CVD) events. Among lipid lowering drugs, statins have a beneficial effect on AS, independent of their hypolipidaemic effect. Based on 3 meta-analyses and other studies, this effect is compound- and doserelated. Potent statins at high doses are more effective than less powerful statins. Ezetimibe (± statin) also seems to decrease AS in patients with dyslipidaemia. Fibrates have no effect on AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have data that beneficially affect all AS risk factors, suggesting a beneficial effect on artery compliance. However, there is no direct measurement of their effect on AS indices. In patients with dyslipidaemia, prescribing high dose statins (± ezetimibe) will not only decrease low-density lipoprotein cholesterol levels but also improve AS (in addition to other effects). This effect on AS may contribute to the observed reduction in vascular events.

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