Application of a New Processing Method to Post-LDL-apheresis Data

Our aim was to elaborate a method to optimise treatment intervals for the individual low-density lipoprotein (LDL)-apheresis treated patients. After each treatment, plasma LDL concentrations show a time-related increase with a decreasing speed until a maximum level.We searched to interpret the post-LDL-apheresis experimental data trend as the physical process that produces the observed curve, so that the fitting presupposed theoretical function is a direct consequence of the physic process, because to establish the better time. Applying the proposed fitting method to a succession of 15 samples obtained from the mean of six plasmapheresis executed on five different subjects, small estimate standard error (5 mg/dl) and relative error (1.7%) with a dispersion evidently related to the experimental error were observed. Obviously, applying the same method to a single case, the dispersion is more marked (relative error <5%), with a SE of 10-13 mg/dl, even though the aspect of a casual phenomenon is conserved. Our physical interpretation appears to be a practical model to predict the LDL-rebound kinetic of the single patient.

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6th Hellenic Congress in Athens, of the Hellenic Atherosclerosis Society, on the 04-06 December 2014 Novel Pharmacologic Treatments of Familial Hypercholesterolaemia

The Open Cardiovascular Medicine Journal ◽

10.2174/1874192401509010073 ◽

2015 ◽

Vol 9 (1) ◽

pp. 73-77

Author(s):

Athyros VG

Keyword(s):

Familial Hypercholesterolaemia ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Automatic Device ◽

Loss Of Function ◽

Ldl Apheresis ◽

Cvd Risk ◽

Atherosclerosis Risk In Communities ◽

Lipid Disorder ◽

Pharmacologic Treatments

Familial hypercholesterolaemia (FH) is the most common inherited monogenic lipid disorder. It is caused by mutations of genes related to low density lipoprotein (LDL) receptors, apolipoprotein B or proprotein convertase subtilisin/kexin type 9 (PCSK9). Homozygous FH (HoFH; 1/400,000 births) is treated by LDL apheresis. Recently lomitapide has been used for the treatment of HoFH as a monotherapy or in addition to LDL apheresis. Heterozygous FH (HeFH), 1/250-1/200 births, is associated with an increased cardiovascular disease (CVD) risk. The main treatment for HeFH has been high doses of high intensity statins plus ezetimibe. However, this is not usually enough to attain LDL-C targets, especially in those with overt CVD or equivalents (LDL-C goal of<70 mg/dl). Data from the Atherosclerosis Risk in Communities study showed that loss of function mutations of PCSK9 were associated with a 28% lower LDL-C level and an 88% reduction in the risk of CVD in blacks, while in whites these numbers were 15% and 47%, respectively. This led to the development of technology to block PCSK9 with monoclonal human antibodies (e.g. evolocumab and alirocumab). These antibodies have been shown in phase II and III trials to be safe and to produce reductions in LDL-C levels by around 60% either as monotherapy or on top of optimal therapy with statins and ezetimibe. These antibodies are administered subcutaneously every 2 weeks with an automatic device. Anti-PCSK9 antibodies are expected to be licensed soon (? in 2015) and are considered by many as “the statins of the 21st century”.

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Scavenger receptors: a key player in cardiovascular diseases

BioMolecular Concepts ◽

10.1515/bmc-2012-0003 ◽

2012 ◽

Vol 3 (4) ◽

pp. 371-380 ◽

Cited By ~ 6

Author(s):

Mohammad Z. Ashraf ◽

Anita Sahu

Keyword(s):

Cardiovascular Diseases ◽

Apoptotic Cell ◽

Low Density Lipoprotein ◽

Scavenger Receptor ◽

Density Lipoprotein ◽

Vascular Lesions ◽

Great Promise ◽

Term Therapy ◽

Membrane Glycoproteins ◽

The Individual

AbstractThe scavenger receptor (SR) super family consists of integral membrane glycoproteins that are involved in recognition of polyanionic structures of either endogenous (e.g., oxidized low-density lipoprotein) or exogenous (e.g., bacterial lipopolysaccharides) origin. SRs are structurally diverse and can be classified into seven different classes (A–G) based on the multidomain structure of the individual members. SRs are present on various types of tissues, such as vascular, adipose, and steroidogenic tissues. In addition to modified lipoprotein uptake, these proteins are also known to regulate apoptotic cell clearance, initiate signal transduction, and serve as pattern recognition receptors for pathogens. Different SRs are involved in many physiological and pathological processes; more importantly, the function of SRs is highly implicated in the initiation and progression of atherosclerotic plaque. Targeting the SR gene products that mediate the response to and uptake of modified lipids holds great promise in the prevention of cardiovascular diseases. Inhibition of SR expression using a combined gene therapy and RNA interference strategy also appears to be an option for long-term therapy. The present review focuses on the involvement of SRs in atherosclerosis, thrombosis, and other cardiovascular diseases. Moreover, the role of SRs is not restricted to vascular lesions; it is also implicated in a number of different cellular functions.

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Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults

European Journal of Preventive Cardiology ◽

10.1177/2047487319899621 ◽

2020 ◽

Vol 27 (15) ◽

pp. 1617-1626 ◽

Cited By ~ 1

Author(s):

Roshni Joshi ◽

S Goya Wannamethee ◽

Jorgen Engmann ◽

Tom Gaunt ◽

Deborah A Lawlor ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Odds Ratio ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Increased Risk ◽

The Individual

Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. Methods Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. Results The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. Conclusions Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

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Biological variability of cholesterol, triglyceride, low- and high-density lipoprotein cholesterol, lipoprotein(a), and apolipoproteins A-I and B

Clinical Chemistry ◽

10.1093/clinchem/40.4.574 ◽

1994 ◽

Vol 40 (4) ◽

pp. 574-578 ◽

Cited By ~ 66

Author(s):

S M Marcovina ◽

V P Gaur ◽

J J Albers

Keyword(s):

High Density Lipoprotein ◽

Ldl Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Biological Variability ◽

Apo B ◽

Lipoprotein A ◽

The Individual

Abstract Biological variability is a major contributor to the inaccuracy of cardiovascular risk assessments based on measurement of lipids, lipoproteins, or apolipoproteins. We obtained estimates of biological variation (CVb) for 20 healthy adults and calculated the percentiles of CVb as an expression of the variability of CVb among individuals for cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (apo) A-I, apo B, and lipoprotein(a) [Lp(a)] by four biweekly measurements of these analytes. The CVb for the group was approximately 6-7% for cholesterol, HDL cholesterol, apo A-I, and apo B; approximately 9% for LDL cholesterol; and 28% for triglyceride. However, for each analyte, there was a considerable variation of CVb among individuals. For all analytes except Lp(a), there was no relation between the individual's CVb and the analyte concentration. Lp(a) was inversely related to CVb, and there was a very wide variation in the CVb for Lp(a) among the participants, ranging from 1% to 51%. The number of independent analyses to perform to accurately assess an individual's risk for coronary artery disease should be determined on the basis of the individual CVb for a given analyte rather than the average CVb.

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A Cellular Receptor of Human Rhinovirus Type 2, the Very-Low-Density Lipoprotein Receptor, Binds to Two Neighboring Proteins of the Viral Capsid

Journal of Virology ◽

10.1128/jvi.77.15.8504-8511.2003 ◽

2003 ◽

Vol 77 (15) ◽

pp. 8504-8511 ◽

Cited By ~ 31

Author(s):

Emmanuelle Neumann ◽

Rosita Moser ◽

Luc Snyers ◽

Dieter Blaas ◽

Elizabeth A. Hewat

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Very Low Density Lipoprotein ◽

Low Density ◽

Lipoprotein Receptor ◽

Low Density Lipoprotein Receptor ◽

The North ◽

Density Lipoprotein Receptor ◽

The Individual ◽

Viral Protein 1

ABSTRACT The very-low-density lipoprotein receptor (VLDL-R) is a receptor for the minor-group human rhinoviruses (HRVs). Only two of the eight binding repeats of the VLDL-R bind to HRV2, and their footprints describe an annulus on the dome at each fivefold axis. By studying the complex formed between a selection of soluble fragments of the VLDL-R and HRV2, we demonstrate that it is the second and third repeats that bind. We also show that artificial concatemers of the same repeat can bind to HRV2 with the same footprint as that for the native receptor. In a 16-Å-resolution cryoelectron microscopy map of HRV2 in complex with the VLDL-R, the individual repeats are defined. The third repeat is strongly bound to charged and polar residues of the HI and BC loops of viral protein 1 (VP1), while the second repeat is more weakly bound to the neighboring VP1. The footprint of the strongly bound third repeat extends down the north side of the canyon. Since the receptor molecule can bind to two adjacent copies of VP1, we suggest that the bound receptor “staples” the VP1s together and must be detached before release of the RNA can occur. When the receptor is bound to neighboring sites on HRV2, steric hindrance prevents binding of the second repeat.

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Low-Density Lipoprotein (LDL) Apheresis

Dyslipidemias - Contemporary Endocrinology ◽

10.1007/978-1-60761-424-1_29 ◽

2015 ◽

pp. 483-497 ◽

Cited By ~ 1

Author(s):

P. Barton Duell

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Ldl Apheresis

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Preoperative Low-Density Lipoprotein Apheresis for Preventing Recurrence of Focal Segmental Glomerulosclerosis after Kidney Transplantation

Journal of Transplantation ◽

10.1155/2018/8926786 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Akihito Sannomiya ◽

Toru Murakami ◽

Ichiro Koyama ◽

Kosaku Nitta ◽

Ichiro Nakajima ◽

...

Keyword(s):

Renal Failure ◽

Kidney Transplantation ◽

Focal Segmental Glomerulosclerosis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Ldl Apheresis ◽

Segmental Glomerulosclerosis ◽

Living Related ◽

Observation Period

Background. Focal segmental glomerulosclerosis (FSGS) often develops rapidly and frequently progresses to renal failure, while the recurrence rate after kidney transplantation is 20–50%. We performed low-density lipoprotein (LDL) apheresis before kidney transplantation in FSGS patients to prevent recurrence. Methods. Five adult patients with chronic renal failure due to FSGS undergoing living related donor kidney transplantation were investigated retrospectively. LDL apheresis was done 1-2 times before transplantation. Postoperative renal function and recurrence of FSGS were assessed. Results. The patients were two men and three women aged 24 to 41 years. The observation period ranged from 60 days to 22 months. Preoperative LDL apheresis was performed once in one patient and twice in four patients. Blood LDL cholesterol levels were normal before LDL apheresis and remained normal both after LDL apheresis and after kidney transplantation. Additional LDL apheresis was performed once in one patient with mild proteinuria after transplantation. The renal graft survived in all patients and there was no evidence of recurrent FSGS. Conclusions. Although the observation period was short, FSGS did not recur in all 5 patients receiving preoperative LDL apheresis. These results suggest that LDL apheresis can be effective in preventing recurrence of FSGS after kidney transplantation.

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Changes in Bradykinin and Prostaglandins Plasma Levels during Dextran-sulfate Low-density-lipoprotein Apheresis

The International Journal of Artificial Organs ◽

10.1177/039139889702000310 ◽

1997 ◽

Vol 20 (3) ◽

pp. 178-183 ◽

Cited By ~ 30

Author(s):

S. Kojima ◽

M. Ogi ◽

Y. Yoshitomi ◽

M. Kuramochi ◽

J. Ikeda ◽

...

Keyword(s):

Plasma Levels ◽

Dextran Sulfate ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Guanosine Monophosphate ◽

Prostaglandin E ◽

Plasma Kallikrein ◽

Low Density ◽

Ldl Apheresis

The negative charges of dextran-sulfate (DS) used for low-density-lipoprotein (LDL) apheresis initiate the intrinsic coagulation pathway in which plasma kallikrein acts on the high-molecular-weight kininogen to produce large amounts of bradykinin. This study was undertaken to assess whether bradykinin generated during DS LDL apheresis has any physiologic effects in vivo. The plasma levels of bradykinin, prostaglandins and cyclic guanosine monophosphate (cGMP) were compared, when either of two anticoagulants, heparin or nafamostat mesilate (NM), was used during DS LDL apheresis. Although anticoagulative action by NM depends on the inhibition of thrombin activity, this substance also inhibits the activity of plasma kallikrein. During apheresis using heparin, the plasma levels of prostaglandin E2 (PGE2) increased significantly (5.6 ± 1.2 (mean ± SE, n=4) pg/ml before apheresis and 33.4 ± 13.2 after apheresis, p < 0.05) in association with an increase in bradykinin levels (17.9 ± 2.6 pg/ml before apheresis and 470 ± 135 after apheresis, p < 0.01). Interestingly, these changes were suppressed during apheresis using NM. There were no appreciable changes in cGMP during DS LDL apheresis with either of the anticoagulants. This finding suggests that bradykinin generated during apheresis has some pathophysiological effects via activation of the prostaglandin system. Our results support the view that in patients taking angiotensin-convertingenzyme inhibitors, the anaphylactoid reaction occurring during apheresis may be caused by an excessive rise in the bradykinin levels.

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Use of serum cholesterol/triglyceride ratio to discern for which individuals the Friedewald formula can be used confidently

Clinical Chemistry ◽

10.1093/clinchem/36.9.1673 ◽

1990 ◽

Vol 36 (9) ◽

pp. 1673-1675 ◽

Cited By ~ 13

Author(s):

M González Estrada ◽

C R Rodríguez Ferrer ◽

I R Astarloa ◽

E M Lahera

Keyword(s):

Total Cholesterol ◽

Serum Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Very Low Density Lipoprotein ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Friedewald Formula ◽

The Individual ◽

Low Serum

Abstract The values of low-density lipoprotein cholesterol obtained according to the Friedewald formula (Clin Chem 1972; 18:499-502), or by the De Long transformation (J Am Med Assoc 1986;256:2372-7), were compared with the values obtained when the individual cholesterol/triglyceride ratio of very-low-density lipoprotein was used for estimating the contribution of this lipoprotein to the total cholesterol. We found that these formulas gave the greatest errors for individuals with a low serum cholesterol/triglyceride ratio. We propose criteria for deciding when the numerically calculated value of low-density cholesterol is appropriate, and when it is not.

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