Pathophysiology and clinical significance of atherogenic lipoprotein phenotype and small dense LDL particles

In spite of strong proofs supporting cholesterol hypothesis, serum cholesterol concentration is not a good discriminative factor in assessing the risk of coronary heart disease. The degree of reduction of coronary risk depends also on the level of serum triglycerides. Namely, within metabolic disturbance of triglyceride rich lipoproteins, a reciprocal lipid transfer takes place in the course of delipidation cascade, yielding the remodelling of all the classes of lipoproteins and establishing the so-called atherogenic lipoprotein phenotype (increase in triglycerides, small dense LDL, and apolipoprotein B, and decrease in HDL cholesterol and apolipoprotein A-I). A major part of the atherogenic potential of this phenotype is related to the increase in the number of small dense LDL particles (phenotype B), and not because of the contribution to the serum cholesterol, but due to their lower affinity to LDL receptors, easier penetration to arterial intima, longer retention in subendothelium accelerated oxidation, prompt takeover by macrophages and establishing of endothelial dysfunction.

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The atherogenic lipoprotein phenotype: small dense LDL and lipoprotein remnants in nephrotic range proteinuria

Atherosclerosis ◽

10.1016/s0021-9150(00)00710-3 ◽

2001 ◽

Vol 157 (1) ◽

pp. 211-220 ◽

Cited By ~ 27

Author(s):

C Deighan

Keyword(s):

Small Dense Ldl ◽

Atherogenic Lipoprotein ◽

Atherogenic Lipoprotein Phenotype ◽

Nephrotic Range Proteinuria ◽

Lipoprotein Phenotype

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High disaccharide intake associates with atherogenic lipoprotein profile

British Journal Of Nutrition ◽

10.1017/s0007114511003783 ◽

2011 ◽

Vol 107 (7) ◽

pp. 1062-1069 ◽

Cited By ~ 12

Author(s):

Emily Sonestedt ◽

Elisabet Wirfält ◽

Peter Wallström ◽

Bo Gullberg ◽

Isabel Drake ◽

...

Keyword(s):

Plasma Concentrations ◽

Principal Component ◽

Hdl Cholesterol ◽

Population Based ◽

Lipoprotein Subfractions ◽

Swedish Population ◽

Atherogenic Lipoprotein ◽

Ldl Particles ◽

Atherogenic Lipoprotein Profile ◽

Atherogenic Lipoprotein Phenotype

Increased plasma concentrations of small LDL particles denote an atherogenic lipoprotein phenotype (ALP) that is correlated with increased circulating TAG and reduced HDL-cholesterol. Principal component analyses of subfraction concentrations have previously been used in the Swedish population-based Malmö Diet and Cancer (MDC) cohort to identify three independent components, one pattern representing the ALP. The aim of the present study was to examine the associations between macronutrient intakes and the principal component representing the ALP. We examined 4301 healthy subjects (46–68 years old, 60 % women) at baseline in the MDC cohort. Dietary data were collected using a modified diet history method. Plasma lipoprotein subfractions were measured using a high-resolution ion mobility method. The principal component corresponding to the ALP was significantly associated with a higher intake of disaccharides, and inversely related to protein and alcohol consumption (P < 0·001 for all). The present findings indicate that the ALP may be improved by a low intake of disaccharides, and moderate intakes of protein and alcohol.

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Inter-relationships between small, dense low-density lipoprotein (LDL), plasma triacylglycerol and LDL apoprotein B in an atherogenic lipoprotein phenotype in free-living subjects

Clinical Science ◽

10.1042/cs0970269 ◽

1999 ◽

Vol 97 (3) ◽

pp. 269-276 ◽

Cited By ~ 12

Author(s):

B. A. GRIFFIN ◽

A. M. MINIHANE ◽

N. FURLONGER ◽

C. CHAPMAN ◽

M. MURPHY ◽

...

Keyword(s):

Particle Number ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Free Living ◽

Small Dense Ldl ◽

Atherogenic Lipoprotein ◽

Apoprotein B ◽

Plasma Triacylglycerol ◽

Atherogenic Lipoprotein Phenotype ◽

Lipoprotein Phenotype

A predominance of small, dense low-density lipoprotein (LDL) is a major component of an atherogenic lipoprotein phenotype, and a common, but modifiable, source of increased risk for coronary heart disease in the free-living population. While much of the atherogenicity of small, dense LDL is known to arise from its structural properties, the extent to which an increase in the number of small, dense LDL particles (hyper-apoprotein B) contributes to this risk of coronary heart disease is currently unknown. This study reports a method for the recruitment of free-living individuals with an atherogenic lipoprotein phenotype for a fish-oil intervention trial, and critically evaluates the relationship between LDL particle number and the predominance of small, dense LDL. In this group, volunteers were selected through local general practices on the basis of a moderately raised plasma triacylglycerol (triglyceride) level (> 1.5 mmol/l) and a low concentration of high-density-lipoprotein cholesterol (< 1.1 mmol/l). The screening of LDL subclasses revealed a predominance of small, dense LDL (LDL subclass pattern B) in 62% of the cohort. As expected, subjects with LDL subclass pattern B were characterized by higher plasma triacylglycerol and lower high-density lipoprotein cholesterol (< 1.1 mmol/l) levels and, less predictably, by lower LDL cholesterol and apoprotein B levels (P < 0.05; LDL subclass A compared with subclass B). While hyper-apoprotein B was detected in only five subjects, the relative percentage of small, dense LDL-III in subjects with subclass B showed an inverse relationship with LDL apoprotein B (r =-0.57; P < 0.001), identifying a subset of individuals with plasma triacylglycerol above 2.5 mmol/l and a low concentration of LDL almost exclusively in a small and dense form. These findings indicate that a predominance of small, dense LDL and hyper-apoprotein B do not always co-exist in free-living groups. Moreover, if coronary risk increases with increasing LDL particle number, these results imply that the risk arising from a predominance of small, dense LDL may actually be reduced in certain cases when plasma triacylglycerol exceeds 2.5 mmol/l.

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