Cholesterol Apheresis Research Articles

Management Considerations for Lipid Disorders During Pregnancy

Dyslipidemias including familial hypercholesterolemia and elevated lipoprotein (a) are not uncommon in young women who may desire pregnancy. In all women, abnormal lipid metabolism has been linked to adverse outcomes during pregnancy, including hypertensive disease of pregnancy, gestational diabetes mellitus, and preterm birth. Optimal management of dyslipidemias in pregnant women remains undefined, as statins are contraindicated in this group. Recent literature questions this traditional avoidance of statins, however, as well as explores their potential benefit in pre-eclampsia specifically. In this review, the arsenal of nutrition, bile acid resins, omega-3 fatty acids, and low-density lipoprotein cholesterol apheresis is explored, as are newer therapies like mipomersen and proprotein convertase subtilisin/kexin type 9 inhibitors, for the management of dyslipidemias during pregnancy.

Effects of LDL apheresis on proteinuria in patients with diabetes mellitus, severe proteinuria, and dyslipidemia

Patients with diabetes mellitus and severe proteinuria present with poor renal prognoses, despite improvements in diabetes and kidney disease therapies. In this study, we designed a low-density lipoprotein (LDL)-cholesterol apheresis treatment for patients with diabetic nephropathy (DN)/diabetic kidney disease and severe proteinuria. This was a multicenter prospective LICENSE study to confirm the impact of LDL apheresis on proteinuria that exhibited hyporesponsiveness to treatment. In addition, we sought to determine the efficacy and safety of LDL apheresis by comparing the outcomes to those of historical controls in patients with diabetes, refractory hypercholesterolemia, and severe proteinuria. This was a prospective, multicenter study, including 40 patients with diabetes, severe proteinuria, and dyslipidemia. LDL apheresis was performed 6-12 times over a 12-week period. The primary endpoint was the proportion of patients with a decrease in proteinuria excretion of at least 30% in the 6months after starting therapy. The secondary endpoints included serum creatinine levels and laboratory variables, which were evaluated 4, 6, 12, 18, and 24months after therapy initiation. LDL apheresis was performed on 40 registered patients with diabetes. The proportion of cases in which proteinuria decreased by 30% or more after 6months of LDL apheresis was 25%, which was similar to that of historical controls. The overall survival and end-stage kidney disease-free survival rates were significantly higher in the LICENSE group compared to those in historical controls. Our results suggest that LDL apheresis may be effective and safe for patients with diabetes, proteinuria, and dyslipidemia. Trial registration number: jRCTs042180076.

Abstract 15669: Generation and LDLR Functional Correction of Familial Hypercholesterolemia iPSC With Physiologically Responsive Non-Integrating BAC Vector

Familial Hypercholesterolemia (FH) is a monogenic disorder of low-density lipoprotein receptor (LDLR) dysfunction, resulting in pathological LDL cholesterol levels and accelerated cardiovascular disease. Many FH patients are refractory to pharmacologic therapies and require cholesterol apheresis or liver transplant. Induced pluripotent stem cells (iPSC) are a promising cell-based option for ameliorating such disorders, though clinically relevant approaches for their functional correction remain to be explored. Homozygous FH fibroblasts were used to generate iPSC (FH-iPSC) using non-integrating synthetic modified mRNAs. Pluripotence was confirmed via immunocytochemistry (OCT4, SOX2, SSEA4, TRA 1-60 & TRA 1-81), in vitro spontaneous differentiation, and in vivo teratoma formation. To mitigate LDLR dysfunction, FH-iPSC were non-virally transfected with a physiologically sensitive episomal LDLR BAC-based plasmid, circumventing cytotoxic LDLR over-expression, insertional mutagenesis, and transgene activation. Transfected colonies (FH-iPSC-LDLR) were selected via Hygromycin-B resistance. After six months of continuous culture, the plasmid was rescued by alkaline lysis, isolated, and introduced into CHO-a7 (LDLR-/-) cells. AgeI restriction digest analysis was performed and DiI-LDL uptake qualitatively demonstrated plasmid functionality. FH-iPSC were also differentiated into hepatocyte-like cells (FH-HLC) and tested for definitive endoderm (SOX17, HNF4α, GATA4) and hepatocyte lineage (AFP, Albumin) markers via PCR and immunocytochemistry. FH-HLC stored lipids and cleared Indocyanine Green. Corrected FH-HLC (FH-HLC-LDLR) qualitatively exhibited markedly increased DiI-LDL internalization compared to dysfunctional FH-HLC (Figure 1). These experiments support a proof-of-principle that patient-specific iPSC can be generated and functionally rescued with clinically relevant vectors to produce therapeutic cell lines.

The lipoproteins selections aphereses with LDL Lipopak 400

The lipid lowering is one of the main ways to achieve reduction of the atherosclerosis progress. In the rare patients with homozygous familial hypercholesterolemia low density lipoprotein cholesterol apheresis should be performed as these patients usually have extremely high low density lipoprotein cholesterol concentrations and these patients usually do not, or only insufficiently, respond to statin therapy.

Aggressive Management in A Child With Homozygous Familial Hypercholesterolemia

Homozygous familial hypercholesterolemia is a rare and fatal disease. Twelve year-old girl patient with anginal symptoms and diffuse xanthomas were treated with diet restriction, per oral high dose statins, ezetimibe, low-density lipoprotein cholesterol apheresis and coronary artery bypass grafting. She has been on follow-up visit in stable condition.

Direct Adsorption of Lipoproteins from Whole Blood by Direct Adsorption of Lipoprotein Apheresis: First Experience in Two Hypercholesterolemic Children

Low density lipoprotein (LDL) cholesterol apheresis, combined with lipid lowering drugs, provides a safe and effective means of improving the prognosis of patients with homozygote familial hypercholesterolemia, especially if started before the age of seven. The direct adsorption of lipoprotein (DALI) is the first extracorporeal low density lipoprotein removing system compatible with whole blood. The purpose of the present study was to clarify the efficacy and safety of DALI in children with homozygous familial hypercholesterolemia. Two boys, aged 9 and 15 years, with familial hypercholesterolemia, who were highly resistant to dietary regimes and to drug therapy, were treated with the low density lipoprotein adsorber DALI apheresis once every 2 weeks for 24 weeks. The treated blood volumes for each procedure were 2911 mL (493 +/- SD) and 5982 mL (1129 +/- SD), respectively. In our patients, the acute mean LDL cholesterol reductions were 44.7 +/- 8.9% and 58.8 +/- 4.5%. The corresponding reductions were 42.5 +/- 7.2% and 56 +/- 4.3% for total cholesterol, and 46.5 +/- 17.1% and 55 +/- 7.5% for very low density lipoprotein cholesterol (VLDL-C). There were insignificant losses of high density lipoprotein (12.2 +/- 5.7%, 8.3 +/- 5.5%). Treatment was well tolerated in general, and neither patient suffered from irreversible or long-lasting adverse effects. Our experience with DALI apheresis is encouraging. The present report is the first on the use of DALI in children. Based on this short-term evaluation we think that DALI might be safe and effective in children with homozygote familial hypercholesterolemia, however further evaluation of long-term effects is needed.

A Case of a True Aneurysm of the Brachial Artery in a Patient with a Radio-cephalic Fistula and Cholesterol Apheresis

Aneurysmal dilatation can occur infrequently at the proximal site of an arteriovenous fistula probably because of abnormal wall stresses. However, there might be other intrinsic factors that contribute to aneurysmal formation besides the fistula, because only a very small number of patients with fistulae develop such an aneurysm. We describe herein the histopathological characteristics of a brachial artery aneurysm in a 57-year-old male patient on cholesterol apheresis through a radio-cephalic fistula, and the relationship of the aneurysm with the underlying disease is discussed.

A Case of a True Aneurysm of the Brachial Artery in a Patient with a Radio-cephalic Fistula and Cholesterol Apheresis

Aneurysmal dilatation can occur infrequently at the proximal site of an arteriovenous fistula probably because of abnormal wall stresses. However, there might be other intrinsic factors that contribute to aneurysmal formation besides the fistula, because only a very small number of patients with fistulae develop such an aneurysm. We describe herein the histopathological characteristics of a brachial artery aneurysm in a 57-year-old male patient on cholesterol apheresis through a radio-cephalic fistula, and the relationship of the aneurysm with the underlying disease is discussed.

Effect of low-density lipoprotein cholesterol apheresis on blood viscosity

Few studies have been designed to study the hemodynamic effects of low-density lipoprotein apheresis, especially on whole blood viscosity. Six patients with cardiovascular disease and hypercholesterolemia underwent a single low-density lipoprotein apheresis, resulting in significant reductions in whole blood viscosity at all shear rates.

Shear stress-dependent platelet function after LDL cholesterol apheresis

Background: Platelets play a crucial role in the pathogenesis of acute coronary syndrome (ACS). Thrombus formation with subsequent arterial occlusion is a major determinant in ACS and stroke. Platelets also essentially contribute to the development and progression of atherosclerotic lesions. The aim of the present study was to investigate the effects lipid lowering by LDL apheresis on platelet function in patients with coronary artery disease. Methods: In six patients with angiographically proven coronary artery disease, venous blood samples were obtained before and after LDL cholesterol apheresis. Citrated whole blood (200 μl) was circulated in polystyrene wells at a shear rate of 1875 s −1 for 2 min with a rotating teflon cone. Shear-stress dependent platelet adhesion was measured before and after apheresis. Results: After apheresis, there were significant reductions in LDL (−58%) and HDL (−17%) cholesterol, triglycerides (−43%), fibrinogen (−52%), lipoprotein (a) (−57%) and CRP (−57%) levels. LDL apheresis significantly reduced shear-stress dependent platelet adhesion. Bolus administration of heparin significantly prolonged activated clotting time, but had no significant effect on platelet adhesion or aggregates. Conclusions: In patients with coronary artery disease, shear-stress dependent platelet adhesion is reduced by a single LDL apheresis. In addition to its cholesterol-lowering effect, LDL apheresis reduces circulating levels of fibrinogen and C-reactive protein.

What's new in lipid management?

Statins are the principal agents for managing hyperlipidemia because of their ability to reduce low-density lipoprotein cholesterol (LDL) and triglyceride levels, increase high-density lipoprotein cholesterol (HDL) levels slightly, and decrease clinical events. Nevertheless, not all patients can tolerate the statins or achieve their treatment goals with these drugs. In addition, available statins have only modest effects on HDL, and clinical events still occur despite the best current lipid-lowering agents. Thus, new lipid-lowering agents are required to improve clinical outcomes. These recently or soon to be released agents are stanol esters, which can be incorporated into spreads and other foods and reduce LDL levels up to 15%; colesevelam, a new bile acid sequestrant with a higher potency, fewer adverse effects, and less drug interactions than those of older agents in this class; rosuvastatin, a new statin that reduces LDL levels and increases HDL levels at least more effectively than atorvastatin; and a new class of agents that inhibit cholesterol absorption and are likely to be used in combination with statins. Low-density lipoprotein cholesterol apheresis is another, nonpharmacologic option for patients with severe hyperlipidemia despite maximal medical therapy.