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Objectives: Iron deficiency (ID) and iron deficiency anemia (IDA) are common findings in patients undergoing lipoprotein apheresis (LA). Different intravenous (iv) formulations are used to treat ID in LA patients, however guidelines and data on ID/IDA management in LA patients are lacking. We therefore performed a prospective observational multi-center cohort study of ID/IDA in LA patients, comparing two approved i.v. iron formulations, ferric gluconate (FG) and ferric carboxymaltose (FCM)., Methods: Inclusion criteria were a) serum ferritin <100 μg/L or b) serum ferritin <300 μg/L and transferrin saturation <20%. Patients received either FG (62.5 mg weekly) or FCM (500 mg once in ID or up to 1000 mg if IDA was present) i.v. until iron deficiency was resolved. Efficacy and safety were determined by repeated laboratory and clinical assessment. Iron parameters pre and post apheresis were measured to better understand the pathogenesis of ID/IDA in LA patients., Results: 80% of LA patients treated at the three participating centers presented with ID/IDA; 129 patients were included in the study. Serum ferritin and transferrin levels were reduced following apheresis (by 18% (p < 0.0001) and by 13% (p < 0.0001) respectively). Both FG and FCM were effective and well tolerated in the treatment of ID/IDA in LA patients. FCM led to a quicker repletion of iron stores (p < 0.05), while improvement of ID/IDA symptoms was not different. Number and severity of adverse events did not differ between FG and FCM, no severe adverse events occurred., Conclusions: Our results suggest that FG and FCM are equally safe, well-tolerated and effective in treating ID/IDA in LA patients. These data form the basis for follow-up randomized controlled trials to establish clinical guidelines., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

LDL-apheresis (LDLa) efficacy in the treatment of symptomatic HyperLp(a)lipoproteinemia -HyperLp(a)- has been studied in a multicentre trial. After 3.1+/-2.7 years of weekly and biweekly treatment, the data from 19 patients (males:12; females:7; aged 53.8+/-9.3 years; mean body mass index: 24.6+/-2.3 Kg/m²) were evaluated. Data were collected using the same questionnaire shared by 5 participating centres. A total of 2331 procedures were performed. A mean of 3593.7+/-800.3 ml of plasma or 8115.3+/-2150.1 ml of blood, depending upon the technique used (H.E.L.P., D.A.LI., Dextransulphate, Lipocollect 200), was regularly treated on average every 10.1+/-2.6 days. Baseline mean Lp(a) levels were 172.3+/-153.8 mg/dL. The mean pre-/post-apheresis Lp(a) levels decreased from 124.5+/-107.2 mg/dL (p<0.001 vs baseline) to 34.2+/-40.6 mg/dL (p<0.001 vs pre-). Baseline mean LDL-cholesterol (LDLC) levels were 152.3+/-74.6 mg/dL. The mean pre-/post-apheresis LDLC levels decreased from 130.4+/-61.1 mg/dL (p<0.004 vs baseline) to 41.2+/-25.1 mg/dL (p<0.001 vs pre-). The hypolipidemic drugs given to the patients during LDLa were: ezetimibe+simvastatin, atorvastatin, rosuvastatin, pravastatin, acipimox, and omega-3 fatty acids. 58% of the patients had arterial hypertension. Cigarette smokers were 5.3%. Alcohol intake was present in 21%. 52.6% were physically active. Patients with coronary artery disease (CAD) submitted to coronary catheterization before LDLa were 95%. In 5.5% (#1) CAD recurred despite treatment with LDLa. 79% were submitted to coronary revascularization before LDLa. CAD was: monovasal in 8 patients (42.1%), bivasal in 5 (26.4%), trivasal in 4 (21%), plurivasal in 2 (10.5%). In 94.5% of the sample the lesions were stable (< 0% deviation) over 3.1+/-2.7 years. 37% had both CAD and extra-coronary artery disease. This multicentre study confirmed that long-term treatment with LDLa was at least able to stabilize CAD in the majority of the individuals with symptomatic HyperLp(a)., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Objective: To examine whether the vaccination with low density lipoprotein (LDL) antibodies could have a protective effect on rats developed atherosclerosis through the action of atherogenic diet., Methods: Four groups of rats (ranged 8 and 14) were treated for 8 weeks (13 January 2007 to 9 March 2007) at the animal house, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia, with normal control diet (NC), normal control diet+LDL-Ab (NC +I), atherogenic diet (AT), and atherogenic diet + LDL-Ab (AT+I). Lipid concentrations and other different parameters were measured in serum., Results: The concentrations of total cholesterol in atherogenic rats treated with LDL-Ab (AT+I) (n=9) were significantly decreased from 5.72 +/- 0.21 mmol/l to 1.81 +/- 0.08 mmol/l (p<0.001). Low density lipoprotein-cholesterol concentrations were also significantly decreased in AT+I group (p<0.001), as it dropped by 73% from 3.06 +/- 0.09 mmol/l to 0.84 +/- 0.04 mmol/l. Phospholipids concentrations were also decreased in AT+I group (p<0.01). The concentrations of both HDL-cholesterol and triacylglycerol were not significantly different from their matched groups., Conclusion: Results of the present study showed that treatment of atherogenic rats with LDL-Ab significantly decreased the serum concentrations of TC and LDL-C. Our findings suggest that immunization with LDL-Ab has a protective effect on artherogenic rats.

Noninvasive tools to quantitate transgene expression directly are a prerequisite for clinical gene therapy. We established a method to determine location, magnitude, and duration of low-density lipoprotein (LDL) receptor (LDLR) transgene expression after adenoviral gene transfer into LDLR-deficient Watanabe hypercholesterolemic rabbits by following tissue uptake of intravenously injected (111)In-labeled LDL using a scintillation camera. Liver-specific tracer uptake was calculated by normalizing the counts measured over the liver to counts measured over the heart that represent the circulating blood pool of the tracer (liver/heart (L/H) ratio). Our results indicate that the optimal time point for transgene imaging is 4 h after the tracer injection. Compared with control virus-injected rabbits, animals treated with the LDLR-expressing adenovirus showed seven-fold higher L/H ratios on day 6 after gene transfer, and had still 4.5-fold higher L/H ratios on day 30. This imaging method might be a useful strategy to obtain reliable data on functional transgene expression in clinical gene therapy trials of familial hypercholesterolemia.

Plasma concentrations of cellular adhesion molecules are associated with atherosclerotic diseases and major cardiovascular risk factors. It was shown that LDL-apheresis with dextran sulfate lowers the levels of E-selectin and ICAM-1 in patients with familial hypercholesterolemia. The effects of different LDL-apheresis methods have not been studied yet. Cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, fibrinogen, and the adhesion molecules E-selectin, VCAM-1, and ICAM-1 were measured in 20 patients with coronary heart disease and severe hyperlipoproteinemia immediately before and after regular LDL-apheresis. Treatment was performed by different apheresis methods (direct absorption, DA, n = 6; dextran sulfate adsorption, DS, n = 7; heparin precipitation, HP, n = 7). Rebound data of adhesion molecule levels were obtained from 2 patients of each group. Lipids were reduced similarly in all groups. The concentrations of all adhesion molecules were lowered during apheresis. The reduction of E-selectin (-31 +/- 7 vs. -6 +/- 5 and -6 +/- 5%, respectively, P < 0.001) was most prominent in the patients treated by heparin precipitation. Depending on the method of LDL-apheresis, the concentrations of VCAM-1 and E-selectin in the outlets of the LDL-apheresis columns were significantly lower compared to the concentration in the inlets. Plasma concentrations of adhesion molecules increased to their pre-apheresis values within 2 to 4 days following LDL-apheresis. The reductions of adhesion molecule levels observed during LDL-apheresis are at least partly due to adsorption to the LDL-apheresis column. The extent of absorption depends on the principle of extracorporeal LDL elimination., (Copyright 2002 Wiley-Liss, Inc.)

A 50-year old male patient with familial hypercholesterolemia and hyperlipoproteinemia (a), who underwent low density lipoprotein-apheresis treatment developed heparin-induced thrombocytopenia type II (HIT II). Because heparin is contraindicated in patients with HIT, an alternative LDL-apheresis system and modified anticoagulation regimen was necessary. Treatment was changed to a new system called DALI (direct adsorption of lipids). After confirmation of the diagnosis HIT II, DALI LDL-apheresis was carried out with recombinant-hirudin (lepirudin) and citrate in order to prevent hypercoagulability. Efficient LDL-apheresis therapy with minimum therapeutic blood levels of lepirudin (1.4 mg/dl) was achieved with an initial intravenous bolus of 0.114 mg/kg of lepirudin followed by continuous lepirudin infusion of 0.350 mg/h. Thrombin-antithrombin III complex production was well controlled and other hemostatic markers showed no abnormalities. LDL-cholesterol and lipoprotein(a) concentrations were effectively reduced. R-hirudin offers a novel anticoagulation strategy and is, at present, the only alternative for patients with HIT II requiring LDL-apheresis on a regular basis.

Epidemiologic studies and in vitro experiments indicate that low density lipoprotein (LDL) subtypes differ concerning their atherogenic potential. Small, dense LDL are more atherogenic than large, buoyant LDL. LDL apheresis is a potent therapeutic modality to lower elevated LDL-cholesterol. It is unknown whether such therapy induces a shift in the LDL subtype distribution. In this study we evaluated the influence of LDL apheresis on the LDL subtype distribution in patients with CHD and familial hypercholesterolemia (FH, n = 22), combined hyperlipidemia (CHLP, n = 6), or Lp[a]-hyperlipoproteinemia (Lp[a]-HLP, n = 4) regularly treated by LDL apheresis (immunoadsorption (n = 14), HELP apheresis (n = 8), dextran sulfate adsorption (n = 7), cascade filtration (n = 3)). On the basis of 6 LDL subfractions (d 1.020;-1.057 g/mL) isolated by density gradient ultracentrifugation the LDL-density profile was determined in each patient before and after apheresis. There was a relative increase of LDL-subfractions 1, 2, and 3 (P < 0.01, P < 0. 05, and P < 0.01, respectively) and a concomitant decrease of LDL subfractions 5 and 6 (P < 0.05) after apheresis. Subgroup analysis indicates that the degree of the small, dense LDL reduction was much more prominent in patients with CHLP compared to patients with FH or Lp[a]-HLP, whereas the type of apheresis technique had no effect. The extent of small, dense LDL reduction correlated with the preapheresis concentrations of small, dense LDL and triglycerides but not with the extent of triglyceride reduction.We conclude that LDL apheresis not only decreases LDL mass, but also improves LDL-density profile, particularly in patients with CHLP.

Hyperlipidemia and elevated lipoprotein (a) [Lp(a)] levels have been linked to the development and progression of premature atherosclerosis. Two male caucasian patients (36 and 42 years old) with heterozygous familial hypercholesterolemia and extremely elevated Lp(a) concentrations, resistant to diet regimen and lipid lowering drugs, were treated with LDL-apheresis for 55 months (liposorber system, Kaneka, Japan) and 15 months (immunoadsorption system, special Lp(a) columns, Lipopak, Pocard, Russia). Lp(a) dropped on average by 50%, total cholesterol by 27%, LDL-cholesterol by 42%, triglycerides by 43% and the fibrinogen concentration by 16%. Prior to treatment, both patients had suffered three myocardial infarctions. Four and six coronary angiographies with two and four percutaneous transluminal angioplasties (PTCA) were necessary. Since the treatment with LDL-apheresis neither myocardial infarctions nor cardiac complaints have been observed, and both patients have reported better performance. Available data suggest that LDL-apheresis may be effective in the treatment of patients with extremely high Lp(a) concentration.

A total of 230 patients with neurocirculatory dystonia (NCD) were investigated. Different mental disorders associated with the atherogenic nature of dyslipoproteinemia were revealed in the majority of patients using the clinical scale and MMPI test. Psychotropic agents used for a period of 2-4 mos improved the mental status of these patients, increased exercise tolerance, and decreased blood levels of free fatty acids (FFA). A course of exercise training (graded walking) for 4-6 mos. helped to enhance exercise tolerance, to lower the blood levels of cholesterol, triglycerides, FFA, the total fraction of low- and very low-density lipoproteins, to reduce manifestations of hypochondriasis, depression, and neurasthenia . The results obtained can be used for developing programs of NCD patients' rehabilitation.

An affine hemosorbent, a product of covalent heparin immobilization on a solid matrix, has been proposed for the extraction of atherogenic lipoproteins. The sorbent has high capacity with respect to atherogenic lipoproteins and is selective with other blood constituents. Experimental hemosorption in animals demonstrated rapid sorbent regeneration and satisfactory hemo- and biocompatibility, therefore the new sorbent can be recommended for clinical application.

The authors introduce a new approach in a clinical and experimental research termed immunosorption. They have developed highly specific and selective agarose-conjugated immunosorbent with monospecific goat antibodies against human LDL. The sorbent is used in clinical practice for removal of atherogenic lipoproteins from the patients plasma--LDL apheresis procedure. The advantages of affinity chromatography based on LDL-apheresis over plasma-pheresis and haemosorption are discussed. Nonspecific adsorptive, hydrophobic and electrostatic interactions that take place during haemosorption do not provide the required selectivity, while immunosorption procedure enables minimization of nonspecific adsorption of plasma compounds during LDL-apheresis. Several examples illustrate clinical applications of immunosorption method.