scholarly journals Lipoprotein Signatures of Cholesteryl Ester Transfer Protein and HMG-CoA Reductase Inhibition

2018 ◽  
Author(s):  
Johannes Kettunen ◽  
Michael V. Holmes ◽  
Elias Allara ◽  
Olga Anufrieva ◽  
Pauli Ohukainen ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Triglyceride Composition ◽  
Cholesterol Concentration ◽  
Resonance Spectroscopy ◽  
Low Density ◽  
Triglyceride Content ◽  
Cetp Inhibition

AbstractBackgroundCETP inhibition reduces vascular event rates but confusion surrounds its low-density lipoprotein (LDL)-cholesterol effects. We sought to clarify associations of genetic inhibition of CETP on detailed lipoproteins.Methods and ResultsWe used variants associated withCETP(rs247617) andHMGCR(rs12916) expression in 62,400 Europeans with detailed lipoprotein profiling from nuclear magnetic resonance spectroscopy. Genetic associations were scaled to 10% lower risk of coronary heart disease (CHD). Associations of lipoprotein measures with risk of incident CHD in three population-based cohorts (770 cases) were examined.CETPandHMGCRhad near-identical associations with LDL-cholesterol concentration estimated by Friedewald-equation.HMGCRhad a relatively consistent effect on cholesterol concentrations across all apolipoprotein B-containing lipoproteins.CETPhad stronger effects on remnant and very-low-density lipoprotein cholesterol but no effect on cholesterol concentrations in LDL defined by particle size (diameter 18–26 nm) (-0.02SD 95%CI: -0.10, 0.05 forCETPversus -0.24SD, 95%CI -0.30, -0.18 forHMGCR).CETPhad profound effects on lipid compositions of lipoproteins, with strong reductions in the triglyceride content of all highdensity lipoprotein (HDL) particles. These alterations in triglyceride composition within HDL subclasses were observationally associated with risk of CHD, independently of total cholesterol and triglycerides (strongest HR per 1-SD higher triglyceride composition in very-large HDL 1.35; 95%CI: 1.18, 1.54).ConclusionCETP inhibition does not affect size-specific LDL cholesterol but may lower CHD risk by lowering cholesterol in other apolipoprotein-B containing lipoproteins and lowering triglyceride content of HDL particles. Conventional composite lipid assays may mask heterogeneous effects of lipid-altering therapies.

Platelet Aggregation and Plasma Lipoproteins in Alcoholics During Alcohol Withdrawal

1986 ◽  
Vol 55 (02) ◽  
pp. 173-177 ◽  
Author(s):  
K Desai ◽  
J S Owen ◽  
D T Wilson ◽  
R A Hutton
Keyword(s):  
Platelet Aggregation ◽  
Alcohol Withdrawal ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Plasma Lipoprotein ◽  
Cholesterol Concentration ◽  
Arachidonic Acid Content ◽  
Low Density

SummaryPlatelet aggregation, platelet lipid composition and plasma lipoprotein concentrations were measured each week in a group of seventeen alcoholics, without overt liver disease, for one month, following acute, total alcohol withdrawal. The platelets were initially hypoaggregable but, within 1-2 weeks of cessation of drinking, they became hyperaggregable and then gradually returned towards normal values. Hyperaggregability could not be explained by increases in either the cholesterol or the arachidonic acid content of the platelets. Plasma very-low-density lipoprotein cholesterol levels remained high throughout the study, but the initially raised levels of high-density lipoprotein (HDL) cholesterol fell by 26%. Low-density lipoprotein (LDL) cholesterol concentration rose by 10% after two weeks of withdrawal but then returned to about the starting level. The resulting changes in the plasma LDL-cholesterol: HDL-cholesterol ratio, which had increased by more than 50% after two weeks of abstinence, essentially paralleled the time course of enhanced platelet reactivity in all but four of the alcoholics. These findings suggest that alterations in plasma lipoprotein concentrations during acute alcohol withdrawal may be a contributory factor to the haemostatic disorders present in such patients.

Heterozygous hypobetalipoproteinemia with fasting chylomicronemia

1991 ◽  
Vol 37 (2) ◽  
pp. 296-300
Author(s):  
G Huet ◽  
M C Dieu ◽  
A Martin ◽  
G Grard ◽  
J M Bard ◽  
...  
Keyword(s):  
Isoelectric Focusing ◽  
Apolipoprotein B ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Low Density ◽  
Fasting Serum ◽  
Apolipoprotein C ◽  
Oral Fat Load

Abstract We describe a disorder in which low-density lipoprotein (LDL)-cholesterol and apolipoprotein B are in low concentration (0.47 mmol/L and 0.28 g/L, respectively) and chylomicrons are still present in plasma after an 18-h fast. The d less than 1.006 fraction was isolated by flotation ultracentrifugation and the apolipoproteins were analyzed by electrophoresis, immunoblotting with anti-apolipoprotein B-100 antiserum, and isoelectric focusing. In the d less than 1.006 fraction of the fasting serum, we found an apolipoprotein B form with the same apparent molecular mass as apolipoprotein B-48 and similar in amount to apolipoprotein B-100 (respective percentages, 46% and 54%). The monosialylated form of the apolipoprotein C-III was severely decreased. After an oral fat load, the repartition of the two species of apolipoprotein B did not change greatly (respective percentages, 60% and 40%), and the concentration of serum triglyceride increased only from 1.20 to 1.65 mmol/L.

Effect of simvastatin on plasma lipid and lipoprotein concentrations and low-density lipoprotein metabolism in the nephrotic syndrome

1992 ◽  
Vol 82 (6) ◽  
pp. 701-708 ◽  
Author(s):  
G. L. Warwick ◽  
C. J. Packard ◽  
L. Murray ◽  
D. Grierson ◽  
J. P. Stewart ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Apolipoprotein B ◽  
Cholesterol Synthesis ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Cholesterol Concentration ◽  
Low Density ◽  
Coa Reductase

1. The effect of inhibiting the rate-limiting enzyme (3-hydroxy-3-methylglutaryl-CoA reductase, EC 1.1.1.88) in cholesterol synthesis on plasma lipid and lipoprotein concentrations was investigated in 16 patients with primary glomerular disease, heavy proteinuria, well-preserved renal function and hypercholesterolaemia. 2. Detailed studies of low-density lipoprotein metabolism were performed on eight patients before and after 12 weeks of simvastatin therapy. Radioiodinated tracers were used to quantify the fractional catabolic rate of low-density lipoprotein by apolipoprotein B/E receptors and alternative pathways. 3. Simvastatin produced consistent reductions in total plasma cholesterol concentration (median 36.9%), plasma low-density lipoprotein-cholesterol concentration (43.6%) and apolipoprotein B pool size (29.9%). 4. In contrast, the changes in kinetic parameters of low-density lipoprotein metabolism showed no clear pattern. Although an increase in the receptor-mediated catabolism of low-density lipoprotein was demonstrated in five patients, no change or a slight decrease was seen in three patients. Production rates were not significantly altered, although there was a slight decrease in the median value (from 12.4 to 9.7 mg day−1 kg−1). Plasma lathosterol concentration was reduced in all eight patients (range 34–71%), indirectly confirming significant inhibition of cholesterol synthesis. 5. These results suggest that, as in patients with primary moderate hyperlipidaemia, the significant cholesterol-lowering effect of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in the nephrotic syndrome is accompanied by variable changes in lipoprotein metabolism. The reasons for this heterogeneous response are unclear. This reflects our limited understanding of the metabolic basis of nephrotic hyperlipidaemia and the relationship between hepatic sterol synthesis and plasma lipoprotein kinetics.

Effect of Phenobarbitone on Plasma Apolipoprotein B and Plasma High-Density-Lipoprotein Cholesterol in Normal Subjects

1979 ◽  
Vol 56 (5) ◽  
pp. 501-504 ◽  
Author(s):  
P. N. Durrington
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Normal Subjects ◽  
Cholesterol Concentration ◽  
Low Density ◽  
Plasma High Density ◽  
Normal Men ◽  
Plasma Apolipoprotein

1. Further observations from an earlier study in which phenobarbitone in a dose of 180 mg daily was administered to ten normal men and women for 3 weeks are reported. There was a significant increase in plasma high-denity-lipoprotein (HDL) cholesterol concentration and in the concentration of both total plasma and low-density-lipoprotein (LDL) apolipoprotein B. 2. There was no change in the ratios of the cholesterol: apolipoprotein B and triglyceride: apolipoprotein B in LDL. 3. There was no significant change in plasma very-low-density-lipoprotein (VLDL) apolipoprotein B concentration and the proportion of lipid and apolipoprotein B in VLDL remained unchanged. 4. There was no change in the ratio of HDL:LDL cholesterol concentrations.

scholarly journals Correlation of Small Dense LDL Cholesterol and Apolipoprotein B with LDL Cholesterol and its Clinical Significance in Overweight, Type 2 Diabetes Mellitus and Coronary Artery Disease

2016 ◽  
Vol 14 (2) ◽  
pp. 36-40 ◽  
Author(s):  
Arabinda Mohan Bhattarai ◽  
HS Batra ◽  
Suchit Bandyopadhyay ◽  
Pratibha Misra ◽  
Manushri Sharma ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Apolipoprotein B ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Apo B ◽  
Artery Disease

Introduction: Atherosclerotic Coronary Artery Disease (CAD) is fundamentally related to disorders of lipid metabolism. Health problems like obesity, glucose intolerance and metabolic syndrome increase atherosclerotic CAD risk.  A fraction of Low density lipoprotein cholesterol (LDL) is called small dense low density lipoprotein cholesterol (sdLDL). These particles are more atherogenic because they are taken up more easily by arterial wall, readily oxidized and not easily cleared from plasma. Every LDL particle contain an Apo B molecule.Methods: In this cross sectional study we recruited 100 known cases each of CAD, type 2 diabetes, overweight and 100 age and sex matched healthy controls. We took a detailed case summary along with anthropometric measurements. We measured sdLDL by heparin magnesium precipitation method followed by direct estimation of the LDL in the supernatant.Result: Linear regressive analysis showed positive correlation between sdLDL and Apolipoprotein B (Apo B) with LDL cholesterol (r=0.61, p=0.004), (r=0.754, p=0.0034) respectively. Multiple Comparisons after Kruskalwallis test of sdLDL and Apo B levels of  type 2 diabetes, CAD and overweight with controls were significant (p<0.001).Conclusion: Our findings suggest that the estimation of sdLDL and Apo B provide a complimentary benefit in assessment of cases with CAD, type 2 diabetes and overweight.

scholarly journals Trends in Apolipoprotein B, Non-High-Density Lipoprotein Cholesterol, Low-Density Lipoprotein Cholesterol, and Hemoglobin A1C Among US Adults with Diagnosed Diabetes, 2005-2018

2020 ◽  
Author(s):  
X Wang ◽  
Di Zhu ◽  
Yang Du ◽  
Yangbo Sun ◽  
Linda Snetselaar
Keyword(s):  
High Density Lipoprotein ◽  
Apolipoprotein B ◽  
Hemoglobin A1c ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Low Density ◽  
Apo B ◽  
Cholesterol Goal

Abstract Background: The control of blood glucose and athero­genic cholesterol particle concentrations is fundamental for patients with diabetes. The objective of this study was to examine trends in levels of apolipoprotein B (apo B), non-high-density lipoprotein (non-HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and hemoglobin A1c (A1C) and changes in the proportion of patients who achieved their glycemic and lipid goals between 2005 and 2018.Methods: We conducted a serial cross-sectional analysis of the US nationally representative data from the National Health and Nutrition Examination Surveys form 2005 through 2018. Results: In total, 5536 adults aged 20 years or older with diabetes were included (weighted mean age, 60.2 years; female, 50.1%). Among all adults with diabetes, the age-adjusted mean apo B levels did not decrease significantly from 2005 to 2016 (P =0.077). The age-adjusted mean non-HDL cholesterol levels reduced significantly (P =0.004) from 2005 to 2018. In 2017-2018, 55.3% of patients achieved the A1C goal of <7% and 43.8% achieved the non-HDL cholesterol goal of <130 mg/dl. In 2015-2016, 47.3% achieved the apo B goal of <90 mg/dL, 57.2% achieved the LDL cholesterol goal of <100 mg/dl, while 30.6% achieved all four glycemic and lipid goals. The success rates for achieving the goals of apo B, non-HDL cholesterol, and LDL cholesterol were higher in older compared with younger subjects, while white patients exhibited better glycemic control than Mexican Americans and non-Hispanic black patients.Conclusion: Among adults with diabetes, there was a significant reduction in non-HDL cholesterol level while there was no change in levels of apo B, LDL cholesterol or A1C over the past decade. Nevertheless, large percentages of adults with diabetes continue to have higher levels of apo B, non-HDL cholesterol, LDL cholesterol, and A1C.

Lack of Correlation between the Maximum Low-Density Lipoprotein (Ldl) Receptor Activity of Blood Lymphocytes and Plasma LDL Concentration in Normal Men

1983 ◽  
Vol 65 (1) ◽  
pp. 95-98 ◽  
Author(s):  
C. Cortese ◽  
P. R. Turner ◽  
C. B. Marenah ◽  
U. Sule ◽  
S. Price ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Receptor Activity ◽  
Cholesterol Concentration ◽  
Low Density ◽  
Blood Lymphocytes ◽  
Wide Range

1. Measurements were made of the maximal low-density lipoprotein (LDL) receptor activities of blood lymphocytes from 81 healthy men with a wide range of plasma LDL cholesterol concentrations (1.45-7.55 mmol/l). 2. Receptor activity was quantified by measuring the degradation of 125I-labelled LDL (10 μg of protein/ml) to trichloroacetic acid-soluble material during a 6 h incubation, after derepression of the lymphocytes for 72 h in lipoprotein-deficient medium. 3. No significant correlation existed between LDL receptor activity in vitro and plasma LDL cholesterol concentration in vivo (r = −0.08).

Sign in / Sign up

Export Citation Format

Share Document