Severe hypercholesterolaemia: therapeutic goals and eligibility criteria for LDL apheresis in Europe

Thompson, Gilbert R.; Catapano, Alberico L.; Saheb, Samir; Atassi-Dumont, Marielle; Barbir, Mahmoud; Eriksson, Mats; Paulweber, Bernhard; Sijbrands, Eric J.G.; Stalenhoef, Anton F. H.; Parhofer, Klaus G.

doi:10.1097/mol.0b013e3283402f53

Cited by 101 publications

(91 citation statements)

References 46 publications

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“…The cost-effectiveness of this therapeutic approach requires evaluation, however. Patients considered to have a homozygous FH phenotype should be classified at exceptionally high risk [32], and be referred to a specialist centre for consideration for lipoprotein apheresis [64] or trial of new therapies [8].…”

Section: Diagnosis and Assessment Of Adultsmentioning

confidence: 99%

“…However, all recommended targets are difficult to achieve in the majority of FH patients with currently available treatments [5,8,18], so that the maximal LDL-cholesterol reduction that can be tolerated with therapy is a pragmatic strategy, particularly for higher risk patients with FH. The LDL-cholesterol of homozygotes should accordingly be reduced as much as possible [8,32,64], noting subsequent recommendations on use of apheresis. Therapeutic targets for apoB and non-HDL-cholesterol have not been defined in FH [8], but with co-existent metabolic syndrome or diabetes targets recommended by other expert bodies should be adopted [12-14, 59, 98].…”

Section: Ldl-cholesterol and Related Lipid Targetsmentioning

confidence: 99%

“…Given that patients with homozygous FH have a severe or total deficiency in LDLR function, their response to LDL lowering therapies is usually markedly attenuated [32]. Statins and ezetimibe can lower LDL-cholesterol in homozygous FH by potentially decreasing hepatic secretion of apoB [32,122], but these patients usually require apheresis [32,64]. Homozygous patients with LDLR null mutations (function <2% of normal) are less responsive to pharmacotherapy and have a worse prognosis than those with LDLR defective mutations (function 2-25% of normal) [32].…”

Section: Pharmacologic Therapymentioning

confidence: 99%

“…More data are required on the outcomes of pregnancy in women with FH and on the effect of statins on the foetus in the first trimester [140]; an appropriate registry of patients is recommended [8]. Pregnant women with heterozygous FH and established CHD, or with homozygous FH, should be considered for apheresis [8,9,22,64,142].…”

Section: Potential Medication Toxicitymentioning

confidence: 99%

See 3 more Smart Citations

Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation

Watts

Gidding

Wierzbicki

et al. 2014

International Journal of Cardiology

329

200

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Section: Diagnosis and Assessment Of Adultsmentioning

confidence: 99%

Section: Ldl-cholesterol and Related Lipid Targetsmentioning

confidence: 99%

Section: Pharmacologic Therapymentioning

confidence: 99%

Section: Potential Medication Toxicitymentioning

confidence: 99%

See 2 more Smart Citations

Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation

Watts

Gidding

Wierzbicki

et al. 2014

International Journal of Cardiology

329

200

View full text Add to dashboard Cite

“…Therefore, lipid-lowering drugs and other treatment options have been referenced. For the cases with homozygous familial hypercholesterolemia demonstrating limited or no response to drug therapy, LDL-apheresis is the classical therapy model (24) . Our study has several limitations.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of endothelial function and platelet activation in dyslipidemic children

Uçar¹,

Akçay²,

Kologlu³

et al. 2016

Buch

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Objective: The aim of this study was to determine the parameters of endothelial function and platelet activation in children with familial hypercholesterolemia by measuring plasma homocysteine, asymmetrical dimethyl arginine (ADMA), nitrotyrosine and P-selectin levels. Methods: Thirty-five heterozygous familial hypercholesterolemic patients on statin therapy, 10 homozygous familial hypercholesterolemic patients treated by LDL apheresis and lipid-lowering drugs, and 25 healthy children, all aged between 2 to 16 years were enrolled in this study. Echocardiography was performed and intima-media thickness (IMT), and endotheliumdependent vasodilation parameters were evaluated. LDL apheresis was performed by adsorption method using double-membrane filtration technique. Plasma nitrotyrosine, homocysteine, P-selectin and ADMA levels were determined with an enzyme-linked immunosorbent assay (ELISA) using a commercial kit. Results: Plasma homocysteine (p=0.000), ADMA (p=0.005), nitrotyrosine (p=0.808), p-selectin (p=0.466) levels were lowest in the LDL apheresis group. A positive correlation was detected between homocysteine and intima/media thickness (r=0.334, p=0.043). Showed that LDL apheresis therapy might decrease plasma levels of homocysteine, ADMA, and nitrotyrosine, and might eventually play an important role in the improvement of endothelial dysfunction and platelet activity. Conclusion: Our data showed that at post-LDL apheresis status the homozygous hyperlipidemic children have lower levels of homocysteine, ADMA, and nitrotyrosine, compared with the heterozygous hyperlipidemic children.

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Apolipoprotein B100 is a suppressor of Staphylococcus aureus‐induced innate immune responses in humans and mice

et al. 2012

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Plasma lipoproteins such as LDL (low-density lipoprotein) are important therapeutic targets as they play a crucial role in macrophage biology and metabolic disorders. The impact of lipoprotein profiles on host defense pathways against Gram-positive bacteria is poorly understood. In this report, we discovered that human serum lipoproteins bind to lipoteichoic acid (LTA) from Staphylococcus aureus and thereby alter the immune response to these bacteria. Size-exclusion chromatography and solid-phase-binding analysis of serum revealed the direct interaction of LTA with apolipoproteins (Apo) B100, ApoA1, and ApoA2. Only ApoB100 and the corresponding LDL exerted biological effects as this binding significantly inhibited LTA-induced cytokine releases from human and murine immune cells. Serum from hypercholesterolemic mice or humans significantly diminished cytokine induction in response to S. aureus or its LTA. Sera taken from the patients with familial hypercholesterolemia before and after ApoB100-directed immuno-apheresis confirmed that ApoB100 inhibited LTA-induced inflammation in humans. In addition, mice in which LDL secretion was pharmacologically inhibited, displayed significantly increased serum cytokine levels upon infection with S. aureus in vivo. The present study identifies ApoB100 as an important suppressor of innate immune activation in response to S. aureus and its LTA.

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Severe hypercholesterolaemia: therapeutic goals and eligibility criteria for LDL apheresis in Europe

Cited by 101 publications

References 46 publications

Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation

Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation

Evaluation of endothelial function and platelet activation in dyslipidemic children

Apolipoprotein B100 is a suppressor of Staphylococcus aureus‐induced innate immune responses in humans and mice

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