Unraveling hyperlipidemia type III (dysbetalipoproteinemia), slowly

Schaefer, Juergen R.

doi:10.1038/ejhg.2008.222

Cited by 17 publications

(14 citation statements)

References 6 publications

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“…Greater than 2/3 of the NHANES population was obese or overweight and 1/8 had diabetes mellitus; furthermore, HLP3 participants had higher TG as compared to the general study population across all diagnostic methods. It is likely that genetic, hormonal, and environmental factors such as high fat diet and current obesity and diabetes epidemics are contributing to its increased phenotypic expression in the United States [ 3 , 4 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…These mutaions lead to defective removal of chylomicron remnants and very low-density lipoprotein cholesterol (VLDL-C), promoting premature atherosclerotic cardiovascular disease (ASCVD) [2]. Fewer than 5% of apoE2 homozygotes develop hyperlipidemia [3], and it is thought that additional genetic, hormonal, and environmental factors such as obesity and diabetes are required to precipitate a pathologic hyperlipidemic state [4].…”

Section: Introductionmentioning

confidence: 99%

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Modern prevalence of dysbetalipoproteinemia (Fredrickson-Levy-Lees type III hyperlipoproteinemia)

Pallazola¹,

Sathiyakumar²,

Park³

et al. 2020

aoms

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Introduction: Dysbetalipoproteinaemia (HLP3) is a disorder characterized by excess cholesterol-enriched, triglyceride-rich lipoprotein remnants in genetically predisposed individuals that powerfully promote premature cardiovascular disease if untreated. The current prevalence of HLP3 is largely unknown. Material and methods: We performed cross-sectional analysis of 128,485 U.S. adults from the Very Large Database of Lipids (VLDbL), using four algorithms to diagnose HLP3 employing three Vertical Auto Profile ultracentrifugation (UC) criteria and a previously described apolipoprotein B (apoB) method. We evaluated 4,926 participants from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) with the apoB method. We examined demographic and lipid characteristics stratified by presence of HLP3 and evaluated lipid characteristics in those with HLP3 phenotype discordance and concordance as determined by apoB and originally defined UC criteria 1. Results: In U.S. adults in VLDbL and NHANES, a 1.7-2.0% prevalence is observed for HLP3 with the novel apoB method as compared to 0.2-0.8% prevalence in VLDbL via UC criteria 1-3. Participants who were both apoB and UC criteria HLP3 positive had higher remnant particles as well as more elevated triglyceride/apoB and total cholesterol/apoB ratios (all p < 0.001) than those who were apoB method positive and UC criteria 1 negative. Conclusions: HLP3 may be more prevalent than historically and clinically appreciated. The apoB method increases HLP3 identification via inclusion of milder phenotypes. Further work should evaluate the clinical implications of HLP3 diagnosis at various lipid algorithm cut-points to evaluate the ideal standard in the modern era.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modern prevalence of dysbetalipoproteinemia (Fredrickson-Levy-Lees type III hyperlipoproteinemia)

Pallazola¹,

Sathiyakumar²,

Park³

et al. 2020

aoms

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“…First, the decreased LDLR affinity of apoE2 may cause an upregulation of the LDLR or, second, it may lead to preferential binding of particles containing only apoB (such as LDL), because LDLR binds both apoE and apoB. Third, apoE2 might decrease conversion of VLDL to LDL, thereby reducing LDL-C levels [3,31]. Guidelines consider non-HDL-C and apoB as secondary treatment targets beside LDL-C [16].…”

Section: Discussionmentioning

confidence: 99%

Vascular risk factors, vascular disease, lipids and lipid targets in patients with familial dysbetalipoproteinemia: A European cross-sectional study

et al. 2015

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“…Specialised centres in dyslipidaemia will be able to refine diagnosis and management, including dietary and pharmaceutical therapy. Owing to the uncommon nature of this disease, a registry may be useful 150 . An investigation into additional mutations that are candidates for dysbetalipoproteinaemia 151 indicated that additional mutations are unlikely to be found.…”

Section: Future Developments In Dysbetalipoproteinaemiamentioning

confidence: 99%

Dysbetalipoproteinaemia: A mixed hyperlipidaemia of remnant lipoproteins due to mutations in apolipoprotein E

Marais

Solomon

Blom

2014

Critical Reviews in Clinical Laboratory Sciences

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Atherosclerosis is strongly associated with dyslipoproteinaemia, and especially with increasing concentrations of low-density lipoprotein and decreasing concentrations of high-density lipoproteins. Its association with increasing concentrations of plasma triglyceride is less clear but, within the mixed hyperlipidaemias, dysbetalipoproteinaemia (Fredrickson type III hyperlipidaemia) has been identified as a very atherogenic entity associated with both premature ischaemic heart disease and peripheral arterial disease. Dysbetalipoproteinaemia is characterized by the accumulation of remnants of chylomicrons and of very low-density lipoproteins. The onset occurs after childhood and usually requires an additional metabolic stressor. In women, onset is typically delayed until menopause. Clinical manifestations may vary from no physical signs to severe cutaneous and tendinous xanthomata, atherosclerosis of coronary and peripheral arteries, and pancreatitis when severe hypertriglyceridaemia is present. Rarely, mutations in apolipoprotein E are associated with lipoprotein glomerulopathy, a condition characterized by progressive proteinuria and renal failure with varying degrees of plasma remnant accumulation. Interestingly, predisposing genetic causes paradoxically result in lower than average cholesterol concentration for most affected persons, but severe dyslipidaemia develops in a minority of patients. The disorder stems from dysfunctional apolipoprotein E in which mutations result in impaired binding to low-density lipoprotein (LDL) receptors and/or heparin sulphate proteoglycans. Apolipoprotein E deficiency may cause a similar phenotype. Making a diagnosis of dysbetalipoproteinaemia aids in assessing cardiovascular risk correctly and allows for genetic counseling. However, the diagnostic work-up may present some challenges. Diagnosis of dysbetalipoproteinaemia should be considered in mixed hyperlipidaemias for which the apolipoprotein B concentration is relatively low in relation to the total cholesterol concentration or when there is significant disparity between the calculated LDL and directly measured LDL cholesterol concentrations. Genetic tests are informative in predicting the risk of developing the disease phenotype and are diagnostic only in the context of hyperlipidaemia. Specialised lipoprotein studies in reference laboratory centres can also assist in diagnosis. Fibrates and statins, or even combination treatment, may be required to control the dyslipidaemia.

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Unraveling hyperlipidemia type III (dysbetalipoproteinemia), slowly

Cited by 17 publications

References 6 publications

Modern prevalence of dysbetalipoproteinemia (Fredrickson-Levy-Lees type III hyperlipoproteinemia)

Modern prevalence of dysbetalipoproteinemia (Fredrickson-Levy-Lees type III hyperlipoproteinemia)

Vascular risk factors, vascular disease, lipids and lipid targets in patients with familial dysbetalipoproteinemia: A European cross-sectional study

Dysbetalipoproteinaemia: A mixed hyperlipidaemia of remnant lipoproteins due to mutations in apolipoprotein E

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