OBJECTIVE: In heterozygous Familial Hypercholesterolemia (FH) woman atherosclerotic cardiovascular disease occurs 20-years earlier respect woman without FH while homozygous FH women may suffer from atherosclerotic cardiovascular disease even in childhood. Lipoprotein apheresis, a therapeutic \"last chance saloon\", is a well-tolerated procedure that markedly lowers LDL-cholesterol and Lp(a) levels in patients who do not achieve acceptable levels with maximal lifestyle and drug therapy.
RESULTS: The experience of LA treatment in 3 female homozygous FH patients was described. Moreover, an explore analysis on pre and post-LA hormonal levels was performed in 8 HeFH women showing a significant improvement in the atherogenic lipid profile (total cholesterol -56%, LDL cholesterol -71%, triglycerides -72%, Apo B lipoprotein -69%, Lp(a) -59%;) and a reduction of FSH and LH values (FSH - 28%, LH -31%).
CONCLUSIONS: Women with FH experience specific barriers to care, including underrepresentation in research, significant underestimation of risk, and discontinuation of therapy during pregnancy. Therefore, in this study, we investigated the possible effects of LA treatment on plasma FSH and LH levels.

BACKGROUND: Elevated lipoprotein(a) (Lp(a)) is an established risk factor for cardiovascular disease (CVD). To date, the only approved treatment to lower Lp(a) is lipoprotein apheresis (LA). Previous studies have demonstrated that LA is effective in reducing cardiovascular (CV) risk in patients with elevated low-density lipoprotein cholesterol (LDL-C) and/or Lp(a). Here we report our long-term experience with LA and its effectiveness in reducing CVD events in patients with elevated Lp(a).
METHODS: This retrospective open-label, single-center study included 25 individuals with Lp(a) elevation >60 mg/dL and LDL-C < 2.59 mmol/L who had indication for LA. The primary endpoint of this study was the incidence of any CV event (determined by medical records) after initiation of LA.
RESULTS: Mean LA treatment duration was 7.1 years (min-max: 1-19 years). Median Lp(a) was reduced from 95.0 to 31.1 mg/dL after LA (-67.3 %, p < 0.0001). Mean LDL-C was reduced from 1.85 to 0.76 mmol/L after LA (-58.9 %, p < 0.0001). Prior LA, 81 CV events occurred in total (0.87 events/patient/year). During LA, 49 CV events occurred in total (0.24 events/patient/year; -0.63, p = 0.001). Yearly major adverse cardiac event (MACE) rate was reduced from 0.34 to 0.006 (-0.33, p = 0.0002). Similar results were obtained when considering only individuals with baseline LDL-C below 1.42 mmol/L.
CONCLUSIONS: In this observational study of a heterogeneous CV high-risk cohort with elevated Lp(a), LA reduced Lp(a) levels and was paralleled by a decrease in CV events and MACE. We recommend LA for patients with high Lp(a) who still have CV events despite optimal lipid-lowering medication and lifestyle changes.

BACKGROUND: Extracellular vesicles (EVs) have been identified as playing a role in atherosclerosis.
METHODS: A group of 37 hypercholesterolemic patients with atherosclerotic cardiovascular diseases (ASCVD) and 9 patients requiring hemodialysis (HD) were selected for the study.
RESULTS: EVs were comparably reduced by various LA methods (Thermo: 87.66% ± 3.64, DALI: 87.96% ± 4.81, H.E.L.P.: 83.38% ± 11.98; represented as SEM). However, LDL-C (66%; 55%; 75%) and Lp(a) (72%; 67%; 79%) were less effectively reduced by DALI. There was no significant difference in the reduction of EVs when comparing different techniques, such as hemoperfusion (DALI; n = 13), a precipitation (H.E.L.P.; n = 5), and a double filtration procedure (Thermofiltration; n = 19). Additionally, no effect of hemodialysis on EVs reduction was found.
CONCLUSIONS: The study suggests that EVs can be effectively removed by various LA procedures, and this effect appears to be independent of the specific LA procedure used, as compared to hemodialysis.

暂无摘要。

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is used for decades, lowering serum LDL-C levels by more than 70% directly after the treatment. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

OBJECTIVE: Peripheral artery disease (PAD) severely impairs patient prognosis and quality of life (QOL). Although lipoprotein apheresis (LA) has been applied to patients with PAD and elevated serum atherogenic lipoproteins, we hypothesized that LA can be effective for treating PAD even in patients with controlled serum lipoproteins through pleiotropic anti-atherosclerotic effects beyond lipoprotein removal. This study aimed to evaluate the efficacy of LA in patients with treatment-resistant PAD and controlled serum lipoproteins focusing on QOL.
METHODS: In a single-arm prospective study, 30 patients with refractory PAD who had controlled serum lipoproteins underwent sequential LA sessions using dextran sulfate adsorption columns, aiming to complete 10 sessions. The ankle-brachial pressure index (ABI) and vascular QOL (VascuQOL) score were evaluated as the primary outcomes. Secondary outcomes included reactive hyperemia index (RHI) and biological antioxidant potential (BAP) as an endothelial function test and serum antioxidative-capacity evaluation, respectively.
RESULTS: ABI significantly increased after LA sessions (pre-treatment 0.60±0.09 vs. post-treatment 0.65±0.13, p=0.023). Total VascuQOL score (3.7±1.1 vs 4.6±1.1, p＜0.001) and RHI (1.70±0.74 vs 2.34±1.76, p=0.023) significantly improved after the LA sessions. BAP tended to increase after the LA sessions, and the change reached statistical significance 3 months after treatment.
CONCLUSIONS: ABI and QOL improved after a series of LA sessions in conventional treatment-resistant PAD patients with controlled serum lipoprotein levels. Increased antioxidative capacity and ameliorated endothelial function were observed after the LA treatment.

Cardiovascular disease is the leading cause of mortality worldwide. Despite the availability of effective low-density lipoprotein cholesterol (LDL-C) lowering agents, an increased cardiovascular risk is still observed in individuals with therapeutic LDL-C levels. One of these cardiovascular risk factors is elevated plasma lipoprotein(a) (Lp(a)) concentration, which maintains chronic inflammation through the increased presence of oxidized phospholipids on its surface. In addition, due to its 90 percent homology with the fibrinolytic proenzyme plasminogen, Lp(a) exhibits atherothrombotic effects. These may also contribute to the increased cardiovascular risk in individuals with high Lp(a) levels that previous epidemiological studies have shown to exist independently of LDL-C and other lipid parameters. In this review, the authors overview the novel therapeutic options to achieve effective Lp(a) lowering treatment, which may help to define tailored personalized medicine and reduce the residual cardiovascular risk in high-risk patients. Agents that increase LDL receptor expression, including statins, proprotein convertase subtilisin kexin type 9 inhibitors, and LDL production inhibitors, are also discussed. Other treatment options, e.g., cholesterolester transfer protein inhibitors, nicotinic acid derivatives, thyroid hormone mimetics, lipoprotein apheresis, as well as apolipoprotein(a) reducing antisense oligonucleotides and small interfering RNAs, are also evaluated.

暂无摘要。

OBJECTIVE: In Familial Hypercholesterolemia (FH), female atherosclerotic cardiovascular disease occurs 20 years earlier than in women without FH. The aim of this study is to describe the differences in lipoprotein apheresis (LA), a last therapeutic option, in terms of efficacy, safety and clinical outcomes between the two sexes.
METHODS: Sex related differences were analysed in 31 subjects in on LA treatment with FH and not achieving LDL-cholesterol and/or Lp(a) target values on maximum lipid-lowering therapies. Moreover, sex related differences in time to major cardiovascular event (MACE) was investigated in 68 subjects, with at least one year of follow-up.
RESULTS: Among the 31 patients currently undergoing LA treatment who did not achieve LDL-cholesterol and/or Lp(a) target values, no differences in comorbidity were recorded despite a worse pre-LA treatment lipid profile (LDL-C 77 ± 60 mg/dl in males vs. 128 ± 105 mg/dl in females; p 0.025) and a longer mean inter-apheresis interval (17 ± 4 days in males vs. 19 ± 5 days in females; p 0.012) reported in females compared to males. Additionally, in comparison with men, it was found that the time between the first cardiovascular event and the beginning of LA, as well as the age at the beginning of LA, were significantly higher in females than in males (p 0.027 and 0.007, respectively).
CONCLUSIONS: Sex differences in FH subjects not only affect the diagnosis and treatment but also influence varied responses to the treatment itself.

UNASSIGNED: Previous studies have shown that lipoprotein apheresis can modify the plasma lipidome and pro-inflammatory and pro-thrombotic lipid mediators. This has not been examined for treatment with protein convertase subtilisin/kexin type 9 inhibitors such as evolocumab, which are increasingly used instead of lipoprotein apheresis in treatment-resistant familial hypercholesterolemia. The aim of this study was to compare the effects of evolocumab treatment and lipoprotein apheresis on the fatty acid profile and on formation of lipid mediators in blood samples.
UNASSIGNED: We analyzed blood samples from 37 patients receiving either lipoprotein apheresis or evolocumab treatment as part of a previous study. Patients were stratified according to receiving lipoprotein apheresis (n = 19) and evolocumab treatment (n = 18). Serum fatty acid analysis was performed using gas chromatography flame ionization detection and plasma oxylipin analysis was done using liquid chromatography tandem mass spectrometry.
UNASSIGNED: Changing from lipoprotein apheresis to evolocumab treatment led to lower levels of omega-6 polyunsaturated fatty acid (n-6 PUFA) including arachidonic acid, dihomo-γ-linolenic acid and linoleic acid. Moreover, several n-6 PUFA-derived oxylipins were reduced after evolocumab treatment.
UNASSIGNED: Given that arachidonic acid, either directly or as a precursor, is associated with the development of inflammation and atherosclerosis, evolocumab-mediated reductions of arachidonic acid and its metabolites might have an additional beneficial effect to lower cardiovascular risk.