Small dense low-density lipoprotein particles: clinically relevant?

Abstract

Purpose of review: Levels of small, dense low-density lipoprotein (LDL) (sdLDL) particles determined by several analytic procedures have been associated with risk of atherosclerotic cardiovascular disease (ASCVD). This review focuses on the clinical significance of sdLDL measurement.

Recent findings: Results of multiple prospective studies have supported earlier evidence that higher levels of sdLDL are significantly associated with greater ASCVD risk, in many cases independent of other lipid and ASCVD risk factors as well as levels of larger LDL particles. A number of properties of sdLDL vs. larger LDL, including reduced LDL receptor affinity and prolonged plasma residence time as well as greater oxidative susceptibility and affinity for arterial proteoglycans, are consistent with their heightened atherogenic potential. Nevertheless, determination of the extent to which sdLDL can preferentially impact ASCVD risk compared with other apoprotein B-containing lipoproteins has been confounded by their metabolic interrelationships and statistical collinearity, as well as differences in analytic procedures and definitions of sdLDL.

Summary: A growing body of data points to sdLDL concentration as a significant determinant of ASCVD risk. Although future studies should be aimed at determining the clinical benefit of reducing sdLDL levels, there is sufficient evidence to warrant consideration of sdLDL measurement in assessing and managing risk of cardiovascular disease.

Video abstract: https://www.dropbox.com/s/lioohr2ead7yx2p/zoom_0.mp4?dl=0.

Figure 1.. Correlations between plasma levels of immunochemically measured apoB and small LDL-III and large LDL-I.

LDL measurements were made by ion mobility in 804 healthy men and women using data derived from a previously published study (52). Similar results were obtained for small LDL defined as LDL-III plus LDL-IV. r: Pearson correlation coefficient. n.s.: not significant at p <0.05.

Figure 2.. Statistical considerations in assessing interrelationships of large and small LDL.

2A: Bimodality of the distribution LDL peak particle diameter determined by ion mobility in 158 overweight but otherwise healthy participants in a previously published study (41). The clear bars represent phenotype A (peak diameter >217.5 Å) and the cross-hatched bars represent phenotype B. 2B: Concentrations of lbLDL (LDL-I) vs. sdLDL (LDL-III). Red circles are individuals with phenotype B and blue circles are those with phenotype B. The line represents a significant inverse relationship (p<0.001) using a linear regression model. 1C: The same data as in Figure 1B with regression lines determined in a model incorporating an interaction for LDL size phenotype (p<0.001). The positive slope for phenotype B is significant (p<0.001), whereas the relationship for phenotype A is not.