Therapeutic efficiency of lipoprotein(a) reduction by low-density lipoprotein immunoapheresis

doi:10.1016/S0026-0495(98)90278-5

Metabolism

Volume 47, Issue 9, September 1998, Pages 1058-1064

https://doi.org/10.1016/S0026-0495(98)90278-5 Get rights and content

Abstract

This study was performed to investigate the effect of low-density lipoprotein (LDL) immunoapheresis on lipoprotein(a) [Lp(a)] reduction in patients with heterozygous and homozygous familial hyperlipidemia (N = 16) and insufficient response to lipid-lowering agents. By desorption of approximately 5,700 ± 500 mL of plasma, a mean reduction in total cholesterol of 62% (P < .001) and in LDL-cholesterol of 70% (P < .001) was achieved. Lp(a), which was elevated at study entry in seven of these patients (82.1 ± 34.3 mg/dL; range, 48 to 148 mg/dL), was reduced during the initial LDL-apheresis procedure by 74.8% ± 14.1% (P < .001). Long-term apheresis treatment performed at weekly intervals resulted in an mean reduction in Lp(a) pretreatment values to 39.1 ± 28.5 mg/dL (−54%; P < .001). Desorbed Lp(a) was measured at the waste of the columns for 31 apheresis treatments. LP(a) concentration of the column waste was higher in patients with elevated serum Lp(a) pretreatment values as compared with those with Lp(a) serum values within the normal range (elevated Lp(a), 1.420 ± 380 mg; without elevated Lp(a), 235 ± 190 mg; P < .001). The rate of return of Lp(a) following apheresis treatment scheduled at weekly intervals was comparable to that of LDL-cholesterol.

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Cited by (16)

Quality of life in patients treated with lipoprotein apheresis
2016, Journal of Clinical Lipidology
Citation Excerpt :
During the treatment, the patient is immobilized in a semisupine position with the arms kept straight. However, because lipoprotein concentrations commonly increase to former levels rapidly after a first-order kinetic, the treatment must be performed weekly.9,10 At present, LA therapy is the only treatment effective in reducing Lp(a).
Elevated levels of low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] are known risk factors for atherosclerosis and cardiovascular events. Although lipoprotein apheresis (LA) yields optimal outcomes for patients suffering from progressive cardiovascular disease (CVD; coronary, peripheral, and cerebrovascular arterial disease) in the presence of hyperlipoproteinemia (LDL-C > 100 mg/dL or Lp(a) > 60 mg/dL), LA primarily serves as a “last-resort therapy”. Extant findings show that the incidence of new cardiovascular events can be reduced by regular LA. However, it remains unclear whether improvements to the quality of life (QOL) improvement produced by the positive impact on the course of cardiovascular disease outweighs the therapy's time consuming and invasive character. We surveyed 36 patients (32 men and 4 women; age 53 ± 13 years [mean + standard deviation]) undergoing regular LA therapy to assess the effects of apheresis on QOL.
QOL was evaluated in 29 patients on regular lipoprotein apheresis treatment using the Medical Outcomes Study 36-item Short Form Health Survey (SF-36), the Beck Depression Inventory (BDI), and a newly developed questionnaire for assessing QOL in patients undergoing LA.
Patients treated with LA showed lower QOL scores regarding mental aspects and equal scores regarding physical aspects compared to the general population, analogue to the results of patients on hemodialysis (SF-36). Analysis of BDI scores showed apheresis patients did not meet criteria for depression diagnosis, although their depression scores were higher than the general population. Compared to the pre-apheresis period, patients described an improvement of their physical and mental fitness, less angina pectoris and no treatment related pain were reported (apheresis questionnaire).
Apheresis treatment appears to reduce the subjective physical complaints of patients. The partly impaired mental health in patients undergoing apheresis may be attributed to the underlying severe cardiovascular disease. The procedure itself is generally tolerated without major complaints, suggesting the benefits of apheresis exceed any negative effects on patient QOL.
Lipoprotein apheresis: State of the art and novelties
2013, Atherosclerosis Supplements
Citation Excerpt :
Furthermore, nicotinic acid is known to induce often serious side effects even at low dosage, independently of being associated to laropiprant. Several LA methods effectively lower the Lp(a) concentrations [26,53–58]. According to the experience at the Dresden Apheresis center, the Liposorber D method appears to be the most effective with a mean acute reduction rate of more than 80% [58].
Lipoprotein apheresis (LA) is an extracorporeal technique which permits the unselective or specific removal of lipoproteins, namely Low Density Lipoproteins (LDL), as well as other apolipoprotein B100-containing lipoproteins from plasma. LA represents a selective upgrade (with both clinical and metabolic advantages) from conventional forms of extracorporeal therapy such as plasma-exchange (PEX) which was used in the seventies to treat severe hypercholesterolemia. The primary reason for using is the treatment of homo-, double- (or compound) and heterozygous familial hypercholesterolemia (Hoz-, DHtz,- Htz,-FH). This technique has also been shown to be efficacious in the treatment of other severe forms of hyperlipoproteinemia such as: hyperLp(a)lipoproteinemia, the familial combined hyperlipoproteinemia and other varieties associated with an elevated cardiovascular risk (CVR) when used in patients who are poor- or non-responders to pharmacological treatment following specific guidelines for the reduction of cholesterol in plasma. Patients with these severe forms of dyslipidemia and, particularly, those affected by FH are subject to coronary ischemic events and thus require an intensive, efficacious, continuous, and personalized form of therapy. A therapy based solely on current available drugs does not achieve the desired results in the Hoz- and DHtz forms of FH or in approximately 10–20% of the Htz form. For the aforementioned clinical conditions, LA treatment offers a necessary therapeutic approach. LA can also be applied in the prevention of secondary recurrence of coronary ischemic events and of arterial stenosis which appears, rather frequently after vascular surgery (coronary by-pass, percutaneous transluminal angioplasty). Clinical trials have shown that statins provide a major reduction in cardiovascular morbidity and mortality, but often fail to attain desirable LDL-cholesterol target level in Hoz- and DHtz- (Compound) FH high cardiovascular risk patients. Intolerance to statins is also relatively frequent in Htz-FH and non-FH patients. LA has effectively replaced pharmacological cholesterol-lowering therapy for decades. Young high CVR risk patients survived to adulthood thanks only to LA. More recently, promising novel compounds aimed at other molecular targets are being studied for the treatment of severe dyslipidemia: Lomitapide, Mipomersen, PCSK9 inhibitors and HDL-enhancers. It is expected that these potent new agents will be combined with LA in the treatment of the most severe forms of hyperlipidemia.
Differences in the atherogenic risk of patients treated by lipoprotein apheresis according to their lipid pattern
2013, Atherosclerosis Supplements
Citation Excerpt :
Lipoprotein apheresis treatment decreases both LDL-C and Lp(a) levels in conjunction with an insufficiently effective drug therapy [11,12]. Studies have described an acute decrease of Lp(a) (by about 70%) induced by apheresis [3,8,13–16]. Since September 12, 2008, lipoprotein apheresis in patients with isolated increase of Lp(a) ≥ 600 mg/l and progressive cardiovascular complications, such as re-infarction, stent obliteration/occlusion/obstruction has been covered by statutory health insurance in Germany.
In high-risk patients who are already on a maximal lipid-lowering therapy, a lipoprotein apheresis is an important therapeutic option in preventing further progress of vascular complications as it may decrease both LDL-cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) levels.
We looked at the occurrence of cardiovascular events before apheresis and during apheresis in three groups defined by their lipid patterns at the start of an apheresis treatment: Group 1 (LDL-C ≥ 3.4 mmol/l and Lp(a) ≤ 600 mg/l; n = 35), Group 2 (LDL-C ≤ 3.4 mmol/l and Lp(a) ≥ 600 mg/l n = 37) and Group 3 (LDL-C ≥ 3.4 mmol/l and Lp(a) ≥ 600 mg/l; n = 15). Group 2 shows a time period of about 10 years from the first event until the start of apheresis treatment (compared to 2–6 years in the other two groups).
Before the start of apheresis treatment 2.1 events per patient had occurred in Group 1, 3.4 events per patient in Group 2 and 1.8 events per patient in Group 3. Under apheresis therapy just 0.9 events per patient occurred in Group 1, 0.5 in Group 2 and 0.5 in Group 3.
When comparing the two years before the start of apheresis treatment with the first two years under apheresis we saw the following reduction rates of cardiovascular events: Group 1–54%; Group 2–83%; Group 3–83.5%.
Our results show that the reduction of cardiovascular events due to lipoprotein apheresis is especially high in patients with elevated levels of Lp(a) compared to patients with elevated LDL-C only indicating that physicians should be more focused on the risk factor elevated Lp(a).
Lipidfiltration - Safe and effective methodology to perform lipid-apheresis
2004, Transfusion and Apheresis Science
Familial hypercholesterolemia (FH) not adequately responding to diet and drug therapy represents an indication for extracorporeal lipid-apheresis, which has become an highly effective and approved therapy for those patients in several countries. Based on different methodology, five treatment options of lipid-apheresis exist and are in widespread practical use covered by regular reimbursement in Germany. All methods are safe and demonstrate equivalent efficacy of reducing LDL cholesterol with respect to the single apheresis session as well as during long-term treatment. Therefore German reimbursement guidelines leave the choice of the method to the discretion of the apheresis center. Related to properties of the used technology all methods exhibit characteristic patterns of additional plasma protein elimination, which do not impair, but in part may increase the therapeutic benefit of lipid-apheresis. Fibrinogen reduction has to be mentioned as an example. The Lipidfiltration system is based on plasmafiltration previously referred to as membrane differential filtration (MDF), synonymous with double filtration plasmapheresis (DFPP). The new term Lipidfiltration was the result of technological progress in the manufacturing process of the plasmafilter resulting in enhanced sieving characteristics and capacity. The Lipidfiltration system is completed by a specifically designed therapy machine with optimised performance characteristics.
Atorvastatin improves blood rheology in patients with familial hypercholesterolemia (FH) on long-term LDL apheresis treatment
2001, Atherosclerosis
To determine the effect of atorvastatin on blood rheology in patients with familial hypercholesterolemia (FH) on regular LDL apheresis, we prospectively studied the rheological variables fibrinogen, plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit and platelet aggregation in 12 patients (two homozygous, ten heterozygous) before and during treatment with atorvastatin. Baseline values of red cell aggregation and whole blood viscosity were increased in FH patients on regular LDL apheresis compared with healthy controls (P<0.05), whereas fibrinogen, plasma viscosity and hematocrit were similar in the two groups. Treatment with atorvastatin reduced red cell aggregation (P<0.01), whole blood viscosity (P<0.01), plasma viscosity (P<0.01) and platelet aggregation (P<0.05), but caused a slight increase in plasma fibrinogen (by 5%; P<0.01). Our findings suggest that atorvastatin improves blood rheology in patients with FH on regular LDL-apheresis. This improvement in blood flow properties may contribute to the well-known beneficial effects of atorvastatin on cardiovascular risk in patients with severe hyperlipidemia and atherosclerotic vascular disease.
Prospective randomised cross-over comparison of three LDL-apheresis systems in statin pretreated patients with familial hypercholesterolaemia
2000, Atherosclerosis
Various LDL-apheresis systems have gained wider clinical acceptance in recent years to treat patients with severe familial hypercholesterolaemia, in particular in patients with coronary artery disease. For each single device data on efficacy have been provided, but up to now no comparative analysis including the novel direct adsorption of lipoproteins from whole blood has been reported. This prospectively designed cross-over comparison of three commercially available LDL-apheresis systems (immunoadsorption, IMAL; dextran sulphate adsorption, DSA; direct adsorption of lipoproteins, DALI) was performed in eight patients with homozygous (n=3) and heterozygous (n=5) familial hypercholesterolaemia. Removal of atherogenic lipoproteins was highly effective in all systems, for LDL-cholesterol in particular: DSA: −84.3±6.2%; IMAL: −82.1±8.3%; DALI: −76.6±7.2% (P<0.05 as compared DALI versus IMAL and DSA). A reduction in Lp(a) of about 63% was achieved by each device. Loss in HDL-cholesterol was highest with IMAL (−21.3±4.9%, P<0.05) as compared to the other two treatment modalities. DSA decreased HDL-cholesterol by −10.4±6.1% and the DALI system by −12.7±5.0%. Remarkable differences were found for the removal of fibrinogen (DSA: −29.8±14.7%, (P<0.05 versus DALI/IMAL); IMAL: −21.4±10.1% (P<0.05 versus DALI); DALI: −14.8±8.0%). The shortest duration for treatment was achieved by the DALI system (135±20 min, P<0.05 versus IMAL (195±20 min) and DSA (187±29 min)). No side effects were recorded in the total of 96 treatments performed during the study. Long-term observations have yet to prove whether these differences in efficacy may be of clinical relevance.

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Therapeutic efficiency of lipoprotein(a) reduction by low-density lipoprotein immunoapheresis

Abstract

Atherosclerosis

Atherosclerosis

Lancet

Atherosclerosis

Biochem Biophys Res Commun

Atherosclerosis

J Biol Chem

J Biol Chem

Atherosclerosis

Curr Ther Res Clin Exp

Pharmacol Ther

Metabolism

Am J Cardiol

Chem Phys Lipids

Am J Cardiol

Lancet

Lancet

J Lipid Res

Atherosclerosis

Am J Cardiol

The mysteries of lipoprotein (a)

Science

Lipoprotein (a)

Curr Opin Lipidol

Structure and metabolism of lipoprotein (a)

Curr Opin Lipidol

Regulatory mutations in human lipoprotein disorders and atherosclerosis

Curr Opin Lipidol

Genetic architecture of the atherogenic lipoprotein (a)

Ann NY Acad Sci

Lipoprotein (a) and coronary heart disease

Curr Opin Lipidol

Lipoprotein (a): Implications in atherothrombosis

Atherosclerosis

Plasma Lp(a) levels correlate with number, severity, and length-extension of coronary lesions in male patients undergoing coronary arteriography for clinically suspected coronary atherosclerosis

Arterioscler Thromb