Plasma lipoproteins in familial dysbetalipoproteinemia associated with apolipoproteins E2(Arg158-->Cys), E3-Leiden, and E2(Lys146-->Gln), and effects of treatment with simvastatin.
Open accessAbstract
Using a density-gradient ultracentrifugation technique, we analyzed in detail the plasma lipoprotein profiles of 18 patients with familial dysbetalipoproteinemia (FD) who had apolipoprotein (apo) E2(Arg158-->Cys) homozygosity (the E2-158 variant, n = 6), apoE3-Leiden heterozygosity (the E3-Leiden variant, n = 6), or apoE2(Lys146-->Gln) heterozygosity (the E2-146 variant, n = 6), with average plasma cholesterol concentrations of 8.99 +/- 1.34 mmol/L, 9.29 +/- 1.55 mmol/L, and 8.46 +/- 1.10 mmol/L, respectively. No significant differences in sex, age, body mass index, dietary habits, and standard laboratory tests between the three groups were observed. The lipoprotein profiles of all FD patients were characterized by higher concentrations of very-low-density lipoprotein (VLDL) 1, VLDL2, and intermediate-density lipoprotein (IDL) and a higher cholesteryl ester content of VLDL1 and VLDL2 than in 6 normolipidemic control subjects with an average plasma cholesterol concentration of 5.90 +/- 0.53 mmol/L. Major differences between the plasma lipoprotein profiles of patients with the E2-158 variant, the E3-Leiden variant, and the E2-146 variant and the normolipidemic control subjects were in IDL cholesterol concentration (1.70 +/- 0.26, 1.50 +/- 0.26, 1.05 +/- 0.36, and 0.47 +/- 0.14 mmol/L, respectively), LDL cholesterol concentration (1.83 +/- 0.50, 3.09 +/- 0.32, 3.79 +/- 0.76, and 3.77 +/- 0.56 mmol/L, respectively), and the molar ratio of IDL cholesterol to LDL cholesterol (0.98 +/- 0.28, 0.48 +/- 0.04, 0.28 +/- 0.09, and 0.12 +/- 0.03, respectively). After 10 weeks of simvastatin treatment the concentrations of plasma cholesterol, VLDL2 cholesterol, IDL cholesterol, and LDL cholesterol in 3 patients with the E2-158 variant fell significantly, by 46%, 56%, 53%, and 48%, respectively; they also fell in 3 patients with the E3-Leiden variant, by 48%, 54%, 57%, and 52%, respectively, and in 3 patients with the E2-146 variant, by 38%, 55%, 46%, and 35%, respectively. Simvastatin therapy lowered plasma activity of cholesteryl ester transfer protein but had no significant effect on plasma activity of lecithin:cholesterol acyltransferase. It is concluded that patients with FD due to various apoE variants have different lipoprotein profiles, mainly with regard to IDL and LDL levels, although they have a number of similar features of dysbetalipoproteinemia. Simvastatin therapy effectively reduced the plasma concentrations of total cholesterol, VLDL2 cholesterol, IDL cholesterol, and LDL cholesterol in the three groups of patients studied. It is proposed that apoE-dependent defects of the conversion of IDL to LDL may be an important mechanism in the pathophysiology of FD.
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Written from the paper’s full text.
TL;DR
In 18 patients with familial dysbetalipoproteinemia, the E2-158, E3-Leiden, and E2-146 apoE variants showed distinct lipoprotein profiles, especially in IDL and LDL cholesterol, with the IDL/LDL cholesterol ratio separating all groups. Simvastatin 20 mg daily for 10 weeks reduced plasma cholesterol, VLDL2 cholesterol, IDL cholesterol, and LDL cholesterol across variants without significantly changing HDL cholesterol.
Key findings
- All FD groups had higher VLDL1, VLDL2, and IDL cholesterol and higher cholesteryl ester content in VLDL1/VLDL2 than normolipidemic controls. IDL cholesterol was 1.70±0.26 mmol/L for E2-158, 1.50±0.26 for E3-Leiden, 1.05±0.36 for E2-146, and 0.47±0.14 for controls; LDL cholesterol was 1.83±0.50, 3.09±0.32, 3.79±0.76, and 3.77±0.56 mmol/L, respectively.
- The molar ratio of IDL cholesterol to LDL cholesterol distinguished the groups with no overlap: E2-158 0.65–1.44, E3-Leiden 0.44–0.54, E2-146 0.21–0.41, and controls 0.09–0.17.
- In 9 treated patients (3 per variant), 10 weeks of simvastatin 20 mg daily reduced plasma cholesterol, VLDL2 cholesterol, IDL cholesterol, and LDL cholesterol by 46%, 56%, 53%, and 48% in E2-158; 48%, 54%, 57%, and 52% in E3-Leiden; and 38%, 55%, 46%, and 35% in E2-146, respectively. HDL cholesterol did not change significantly.
- CETP activity was higher in E2-158 patients at baseline (145±27 AU) than in controls (77±15 AU); overall FD CETP decreased from 116±37 AU to 85±28 AU with simvastatin. LCAT activity did not differ between patients and controls or before/after treatment.
Methods
- Subjects were 18 patients with FD (6 with E2-158 homozygosity, 6 with E3-Leiden heterozygosity, 6 with E2-146 heterozygosity) and 6 normolipidemic controls from the Leiden University Hospital Lipid Clinic, 1989–1992, studied under standardized dietary conditions. Nine patients (3 per variant) received open-label simvastatin 20 mg daily for 10 weeks.
- Lipoproteins were separated by a two-step density-gradient ultracentrifugation technique: first HDL/LDL/IDL/VLDL, then VLDL1 and VLDL2. Cholesterol, triglyceride, phospholipid, free cholesterol, cholesteryl ester, and protein were measured; LCAT and CETP activities were assayed; apoE phenotype and genotype were determined.
- Results are mean±SD; groups were compared by one-way ANOVA with Scheffé multiple-comparison testing, using log-transformed values for skewed plasma TG, VLDL1 cholesterol, and VLDL2 cholesterol; P<.05 was significant.
Limitations
- The paper does not include a formal limitations section; it notes that two patients were excluded because lipid and lipoprotein levels varied widely over time, presumably due to irregular dietary habits.
- Evident from the text: sample sizes were small (n=6 per FD variant, n=9 treated with simvastatin, n=6 controls), and the simvastatin comparison was not placebo-controlled.
- Evident from the text: inclusion was restricted to patients with plasma cholesterol approximately 9 mmol/L (range 7–12 mmol/L) under optimal dietary conditions, so findings may not generalize to other cholesterol levels or dietary adherence; treatment effects were assessed only over 10 weeks.
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- Findingown data
The molar ratio of IDL cholesterol to LDL cholesterol appeared to be a sensitive parameter in distinguishing between the four groups (three FD variants and normolipidemic subjects).
“As illustrated in Fig 3, the molar ratio of IDL cholesterol to LDL cholesterol appeared to be a sensitive parameter in distinguishing between the groups.”
Quote in the paperSubstantial claim- Rests on an assumption: The normolipidemic control subjects are representative of the general normolipidemic population for lipoprotein profile comparison.
- Findingown data
There was no overlap of the IDL/LDL ratio between the four groups.
“There was no overlap of the IDL/LDL ratio between the four groups.”
Quote in the paperNot a substantial claim- Rests on an assumption: The normolipidemic control subjects are representative of the general normolipidemic population for lipoprotein profile comparison.
- Findingown data
After 10 weeks of simvastatin therapy, the plasma lipoprotein profiles in the 9 treated patients with FD (3 per variant) had changed considerably compared with baseline.
“After 10 weeks of simvastatin therapy, the plasma lipoprotein profiles in the 9 treated patients with FD (3 per variant) had changed considerably compared with baseline (Fig 4).”
Quote in the paperSubstantial claim - Findingown data
IDL cholesterol and LDL cholesterol concentrations in patients with the E3-Leiden variant were between those of patients with the E2-158 variant and those with the E2-146 variant.
“IDL cholesterol and LDL cholesterol concentrations in the patients with the E3-Leiden variant were between those of the patients with the E2-158 variant and those with the E2-146 variant.”
Quote in the paperNot a substantial claim - Findingown data
IDL cholesterol concentrations differed among the groups: E2-158 1.70±0.26, E3-Leiden 1.50±0.26, E2-146 1.05±0.36, and normolipidemic controls 0.47±0.14 mmol/L.
“Major differences between the plasma lipoprotein profiles of patients with the E2-158 variant, the E3-Leiden variant, and the E2-146 variant and the normolipidemic control subjects were in IDL cholesterol concentration (1.70±0.26,1.50±0.26,1.05±0.36,and 0.47±0.14mmol/L, respectively)”
Quote in the paperSubstantial claim- Rests on an assumption: The normolipidemic control subjects are representative of the general normolipidemic population for lipoprotein profile comparison.
- Findingown data
The plasma concentrations of TC, VLDL2 cholesterol, IDL cholesterol, and LDL cholesterol fell considerably in each patient with FD, irrespective of the apoE variant.
“As illustrated in Fig 5, the plasma concentrations of TC, VLDL2 cholesterol, IDL cholesterol, and LDL cholesterol fell considerably in each patient with FD, irrespective of the apoE variant.”
Quote in the paperSubstantial claim - Findingown data
Any pair of means of the IDL/LDL ratio was significantly different from the others at the P<.05 level.
“Any pair of means was significantly different from the others at the P< .05level.”
Quote in the paperNot a substantial claim- Rests on an assumption: The normolipidemic control subjects are representative of the general normolipidemic population for lipoprotein profile comparison.
- Findingown data
LDL cholesterol concentrations differed among the groups: E2-158 1.83±0.50, E3-Leiden 3.09±0.32, E2-146 3.79±0.76, and normolipidemic controls 3.77±0.56 mmol/L.
“LDL cholesterol concentration (1.83±0.50,3.09±0.32,3.79±0.76,and 3.77±0.56mmol/L, respectively)”
Quote in the paperSubstantial claim- Rests on an assumption: The normolipidemic control subjects are representative of the general normolipidemic population for lipoprotein profile comparison.
- Findingown data
No differences between the three groups of patients with FD were found with regard to the relative lipid and lipoprotein changes during simvastatin therapy.
“No differences between the three groups of patients with FD were found with regard to the relative lipid and lipoprotein changes during simvastatin therapy (Fig 6).”
Quote in the paperSubstantial claim - Findingown data
The activity of CETP was lower in all patients during simvastatin therapy.
“The activity of CETP was lower in all patients during simvastatin therapy (Fig 7).”
Quote in the paperNot a substantial claim - Findingown data
Simvastatin therapy did not change the HDL cholesterol concentration significantly in the three groups of patients.
“Simvastatin therapy did not change the HDL cholesterol concentration significantly in the three groups of patients.”
Quote in the paperNot a substantial claim - Findingown data
Overall, the activity of CETP in the plasma of the patients with FD decreased significantly from 116±37 AU at baseline to 85±28 AU after simvastatin therapy.
“Overall, the activity of CETP in the plasma of the patients with FD decreased significantly from 116±37 AU at baseline to 85±28 AU after simvastatin therapy.”
Quote in the paperNot a substantial claim - Study design and conductreasoning
All data presented in this study were obtained under standardized dietary conditions.
“All data presented in this study were obtained under standardized dietary conditions.”
Quote in the paperSubstantial claim - Study design and conductown data
No significant differences in sex, age, body mass index, dietary habits, and standard laboratory tests between the three groups were observed.
“No significant differences in sex, age, body mass index, dietary habits, and standard laboratory tests between the three groups were observed.”
Quote in the paperNot a substantial claim - Study design and conductown data
None of the patients appeared to have renal, thyroid, or liver disease, as assessed by physical examination and routine laboratory tests.
“None of the patients appeared to have renal, thyroid, or liver disease, as assessed by physical examination and routine laboratory tests.”
Quote in the paperSubstantial claim - Premisecitation
More than 90% of patients with FD are homozygous for apoE2(Arg158->Cys).
“More than 90% of patients with FD are homozygous for apoE2(Argl58->Cys).7”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [7]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
The lipoprotein abnormalities in the plasma of individuals with the E2-158 variant were related to an impaired conversion of IDL to LDL.
“We proposed that the lipoprotein abnormalities in the plasma of individuals with the E2-158 variant were related to an impaired conversion of IDL to LDL, a hypothesis supported by in vivo studies.20 ' 22”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [20]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [22]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Study design and conductown data
All other patients had minimal intraindividual variability in lipoprotein levels under optimal dietary conditions, as evaluated by repeated lipid analysis over an interval of at least 2 months.
“All other patients had minimal intraindividual variability in lipoprotein levels under optimal dietary conditions (see below), as evaluated by repeated lipid analysis over an interval of at least 2 months.”
Quote in the paperSubstantial claim - Study design and conductown data
The three groups of patients with FD were comparable with regard to age, sex, and several clinical and biochemical characteristics.
“The three groups of patients with FD were comparable with regard to age, sex, and several clinical and biochemical characteristics.”
- Also stated in: § Results · plain
“Thus, the three groups of patients were comparable with regard to several clinical and biochemical parameters.”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Premisecitation
apoE2(Arg158->Cys), the E2-158 variant, has a binding affinity to the LDL receptor less than 2% that of apoE3 and apoE-12.
“that apoE2(Argl58-»Cys), the E2-158 variant, has a binding affinity to the low-density lipoprotein (LDL) receptor less than 2% that of apoE3 and apoE-l 2 -7”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [2]
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- cites [3]
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- cites [6]
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- cites [7]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- May combine two claims. 17
- Classified as probably not a substantial claim. 8
May combine two claims.
Findingown dataPatients with the E2-146 variant had a normal LDL cholesterol concentration and a moderately higher IDL cholesterol concentration.
“In contrast, the patients with the E2-146 variant had a normal LDL cholesterol concentration and a moderately higher IDL cholesterol concentration.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe plasma lipoprotein profiles of all FD patients were characterized by higher concentrations of VLDL1, VLDL2, and IDL and a higher cholesteryl ester content of VLDL1 and VLDL2 than in normolipidemic control subjects.
“The lipoprotein profiles of all FD patients were characterized by higher concentrations of very-low-density lipoprotein (VLDL) 1, VLDL2, and intermediate-density lipoprotein (IDL) and a higher cholesteryl ester content of VLDL1 and VLDL2 than in 6 normolipidemic control subjects with an average plasma cholesterol concentration of 5.90±0.53mmol/L.”
- Also stated in: § Results · plain
“The lipoprotein composition of all patients with FD was characterized by high cholesterol concentrations of VLDL1, VLDL2, and IDL compared with normolipidemic control subjects.”
Quote in the paperSubstantial claim- Rests on an assumption: The normolipidemic control subjects are representative of the general normolipidemic population for lipoprotein profile comparison.
- Also stated in: § Results · plain
May combine two claims.
Findingown dataPatients with the E2-158 variant had a substantially lower LDL cholesterol concentration and a markedly higher IDL cholesterol concentration than patients with the other two variants.
“The patients with the E2-158 variant had a substantially lower LDL cholesterol concentration and a markedly higher IDL cholesterol concentration than patients with the other two variants.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe CE content tended to be lower and the TG content tended to be higher in all apoB-containing lipoprotein subtractions of the three groups of patients during simvastatin therapy, although only the change in TG content of VLDL2 of the patients with the E2-158 variant reached statistical significance.
“However, the CE content tended to be lower and the TG content tended to be higher in all apoB-containing lipoprotein subtractions of the three groups of patients during simvastatin therapy, although only the change in TG content of VLDL2 of the patients with the E2-158 variant reached statistical significance.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAll patients with the E2-158 variant were homozygous for the APOE*2(Arg158->Cys) allele, whereas all patients with the E3-Leiden variant and the E2-146 variant were heterozygous for the APOE*3-Leiden and APOE*2(Lys146->Gln) allele, respectively.
“Further analysis of the APOE gene by allele-specific restriction endonudease genotyping with the restriction enzyme Hhal, Pvull, or both revealed that all patients with the E2-158 variant were homozygous for the APOE*2(Argl58-»Cys) allele, whereas all patients with the E3-Leiden variant and the E2-146 variant were heterozygous for the APOE*3-Leiden and APOE*2(Lysl46->Gln) allele, respectively, as”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataSimvastatin treatment was associated with decreases in concentrations of plasma cholesterol, VLDL2 cholesterol, IDL cholesterol, and LDL cholesterol in patients with the E2-158 variant of 46%, 56%, 53%, and 48%, respectively; in patients with the E3-Leiden variant the decreases were 48%, 54%, 57%, and 52%, respectively; and in patients with the E2-146 variant they were 38%, 55%, 46%, and 35%,分别是.
“in the patients with the E2-158 variant of 46%, 56%, 53%, and 48%, respectively; in the patients with the E3-Leiden variant the decreases were 48%, 54%, 57%, and 52%, respectively, and in the patients with the E2-146 variant they were 38%, 55%, 46%, and 35%, respectively.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe concentrations of plasma TG and VLDL1 cholesterol tended to decrease in the three groups taking simvastatin, but these changes did not reach statistical significance except for the plasma TG concentration of patients with the E2-146 variant.
“The concentrations of plasma TG and VLDL1 cholesterol tended to decrease in the three groups taking simvastatin, but these changes did not reach statistical significance except for the plasma TG concentration of patients with the E2-146 variant.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataDuring simvastatin treatment, no significant changes in the compositions of VLDL1, IDL, and LDL were observed, and only minor changes in the composition of VLDL2 were found.
“During simvastatin treatment, no significant changes in the compositions of VLDL1, IDL, and LDL were observed, and only minor changes in the composition of VLDL2 were found.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataNo differences in the plasma activity of LCAT were observed between the patients (106±22 AU) and normolipidemic control subjects (101±6 AU) or between the patients before (106±22 AU) and during (93±16 AU) simvastatin therapy.
“No differences in the plasma activity of LCAT were observed between the patients (106 ±22 AU) and normolipidemic control subjects (101 ±6 AU) or between the patients before (106±22 AU) and during (93±16 AU) simvastatin therapy (Fig 7).”
Quote in the paperNot a substantial claim- Rests on an assumption: The normolipidemic control subjects are representative of the general normolipidemic population for lipoprotein profile comparison.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataTreated patients reported good compliance, and none experienced any side effects.
“Treated patients reported good compliance, and none experienced any side effects.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataNo changes in routine laboratory test results, dietary habits, or body weight were observed during simvastatin treatment.
“No changes in routine laboratory test results, dietary habits, or body weight were observed.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenNone took lipid-lowering drugs or any other drugs that might interfere with lipoprotein metabolism for at least 6 weeks before blood samples were taken for the analysis of the lipoprotein profile.
“None took lipid-lowering drugs or any other drugs that might interfere with the lipoprotein metabolism for at least 6 weeks before blood samples were taken for the analysis of the lipoprotein profile (except for 9 patients who received simvastatin therapy; see below).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataThe within-day coefficients of variation were 4.5% for LCAT and 2.7% for CETP.
“The within-day coefficients of variation were 4.5% for LCAT and 2.7% for CETP.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.
Study design and conductnone givenThe measured activities of LCAT and CETP reflect the activity of the enzyme and transfer protein (measured under optimal conditions) and are independent of endogenous plasma lipoproteins.
“The measured activities reflect the activity of the enzyme and transfer protein (measured under optimal conditions) and are independent of endogenous plasma lipoproteins.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationSimvastatin, a HMG-CoA reductase inhibitor, has been reported to reduce plasma concentrations of lipids and lipoproteins in patients with FD associated with the E2-158 variant.
“simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that has been reported to reduce plasma concentrations of lipids and lipoproteins in patients with FD associated with the E2-158 variant, 2326 was effective in improving the plasma lipoprotein profiles in these three groups of patients.”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [23]
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- cites [26]
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May combine two claims.
PremisecitationIn the population the majority of individuals homozygous for the E2-158 variant are normocholesterolemic, suggesting that additional endogenous or exogenous factors influence the expression of the disorder.
“However, in the population the majority of individuals homozygous for the E2-158 variant are normocholesterolemic, suggesting that additional endogenous or exogenous factors influence the expression of the disorder.2 ' 7 -11”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [2]
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- cites [7]
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- cites [8]
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- cites [9]
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- cites [10]
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- cites [11]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll patients had normal fasting blood glucose levels.
“All patients had normal fasting blood glucose levels.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataAll patients had plasma cholesterol concentrations between 7 and 12 mmol/L under optimal dietary conditions, and no differences were observed between the average plasma cholesterol concentrations of the three groups of patients.
“All patients whose laboratory results were analyzed in the present study had plasma cholesterol concentrations between 7 and 12 mmol/L under optimal dietary conditions (Table 1), and no differences were observed between the average plasma cholesterol concentrations of the three groups of patients (Table 2).”
Quote in the paperNot a substantial claimMay combine two claims.
Premiseown dataThe E3-Leiden variant had 25% of normal LDL receptor-binding activity and the E2-146 variant had 40%.
“In vitro LDL receptor-binding studies demonstrated that the E3-Leiden variant had 25% of normal binding activity and the E2-146 variant had 40%, providing further evidence that defective apoE binding might be of primary importance in the pathophysiology of FD.”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [2]
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- cites [3]
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- cites [6]
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- cites [7]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataTwo patients were excluded from the study because their lipid and lipoprotein levels varied widely over time, presumably because of irregular dietary habits.
“Two patients (1 with the E3-Leiden variant and 1 with the E2-146 variant) were excluded from the study because their lipid and lipoprotein levels varied widely over time, presumably because of irregular dietary habits.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll assays were performed in duplicate.
“All assays were performed in duplicate.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataNone of the patients had clinical or biochemical signs of secondary hyperlipoproteinemia, and among the three groups no differences in various routine laboratory tests were observed.
“None of the patients had clinical or biochemical signs of secondary hyperlipoproteinemia, and among the three groups no differences in various routine laboratory tests were observed.”
Quote in the paperSubstantial claim
The paper relies on this without support.
The normolipidemic control subjects are representative of the general normolipidemic population for lipoprotein profile comparison.
“Six nonnolipidemic individuals (3 men and 3 women, aged 58.1+9.6 years [mean±SD]) served as control subjects in this study.”
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Molecular Genetics of Obesity and Cardiovascular Diseases
Chagnon, Y. C. (2006) · Fundamental and clinical cardiology · doi:10.3109/9781420018905.008
- Authors
- Zhao, S. P., Smelt, A. H., Van den Maagdenberg, A. M., Van Tol, A., Vroom, T. F., Gevers Leuven, J. A., Frants, R. R., Havekes, L. M., Van der Laarse, A., & Van 't Hooft, F. M.
- Affiliations
- Leiden University (NL)
- Department of Cardiology, Medical Faculty, University of Leiden, Netherlands.
- ORCID
- Zhao, S P
- Venue
- Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
- Published
- 1994-11
- Volume
- 14
- Issue
- 11
- Pages
- 1705-1716
- ISSN
- 1049-8834 (ISSN-L)
- OpenAlex
- W2140186620
- Semantic Scholar
- 275fc058f194da99387acbb95dd46bca7d511841
- Cited by
- 22
- References
- 0
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2017: 2 · 2016: 1 · 2014: 1
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis and Thrombosis A Journal of Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- TNO Repository (submittedVersion)
- Repository hosted by TU Delft Library (TU Delft) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- familial dysbetalipoproteinemia, apolipoprotein E, VLDL, intermediate density lipoprotein, LDL cholesterol, cholesterol esters, simvastatin
- MeSH terms
- Adult, Aged, Apolipoproteins E, Carrier Proteins, Female, Glycoproteins, Humans, Hyperlipoproteinemia Type III, Phosphatidylcholine-Sterol O-Acyltransferase, Lipoproteins, Lovastatin, Male, Middle Aged, Reference Values, Simvastatin, Apolipoprotein E3, Apolipoprotein E2, Cholesterol Ester Transfer Proteins
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