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

Abstract

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.

Metabolic phenotypes of obesity influence triglyceride and inflammation homoeostasis

“…In obesity, adipose tissue dysfunction will eventually lead to abnormalities in lipid metabolism, such as hypertriglyceridaemia (due to decreased TG hydrolysis and increased hepatic very-low-density lipoprotein production), small dense LDL particles, remnant lipoproteins and low HDL-C levels, all associated with a higher risk for the development of cardiovascular diseases [17][18][19][20]. Adipocyte hypertrophy leads to many changes in adipocyte function and production of antiand pro-inflammatory cytokines.…”

Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty‐person/ten‐country panel

“…Nevertheless, it appears that LDL particle number is more important than LDL composition. Thus, in the vast majority of patients with hypertriglyceridaemia, SD-LDL are the dominant subclass, but only a portion of these patients have an elevated apo B [25,66]. The evidence from multiple cross-sectional and prospective studies demonstrates clearly that the risk of vascular disease in patients with hypertriglyceridaemia relates to the level of apo B [15,[67][68][69][70][71][72].…”

Statins for Treatment of Dyslipidemia in Chronic Kidney Disease

“…LDL-C is a heterogeneous group of lipoproteins; for a given serum LDL concentration, there may be a small number of large particles, or a large number of small, dense, cholesterol-poor particles. The size and shape of the latter particles allow them to more easily pass through the endothelial barrier and bind with stronger affinity to the subendothelial matrix (5), perhaps explaining why predominance of this small dense LDL is associated with increased CV risk (6,7). Since each LDL particle contains one ApoB lipoprotein, ApoB levels may be useful for refining risk estimation within a given stratum of LDL-C level.…”