Association Between Small Dense Low-density Lipoproteins and High-density Phospolipid Content in Patients With Coronary Artery Disease With or Without Diabetes

Hanene Aoua, PhD; Ymène Nkaies, PhD; Ali Ben Khalfallah, Prof; Mohsen Sakly, Prof; Ezzedine Aouani, Prof; Nebil Attia, Prof


Lab Med. 2020;51(3):271-278. 

In This Article

Abstract and Introduction


Objective: To evaluate the phospholipid profile in total plasma, non–high-density lipoprotein (HDL), and HDL fractions. We tried to correlate the phospholipid profile to low-density lipoprotein (LDL) size, as reflected by cholesterol content in each LDL subclass.

Methods: We measured small dense LDL-C levels after heparin-magnesium precipitation and measured high-density lipoprotein phospholipid (HDL-P) levels using a colorimetric enzymatic method.

Results: The correlation of the phospholipid profile to small dense LDL-C (sdLDL-C) in patients with coronary problems showed a negative association between small dense low-density lipoprotein (sdLDL) and HDL-P (r = −0.73; P = .02). Moreover, a strong positive correlation was detected between TG and the ratio HDL-P/HDL-C (r = 0.83; P <.001).

Conclusions: HDL phospholipid has an antiatherogenic effect in coronary artery disease with or without diabetes. Further, large LDL modulation seems to be associated with diabetes rather than coronaropathy.


Coronary artery disease (CAD) is one of the most common causes of mortality and morbidity in developed and developing countries.[1] Two main phenotypes, A and B, are defined based on the plasma low-density lipoprotein (LDL) profile.[2] Phenotype A is characterized by the predominance of large buoyant LDL and phenotype B by the predominance of small dense LDL (sdLDL).[3] Predominance of pattern B and a high level of sdLDL particles in plasma is associated with the development of CAD.[4] sdLDL has easier access to the arterial wall and subendothelial space, lower binding affinity for the LDL receptor, longer plasma half-life, greater susceptibility to modification (eg, glycation), and lower resistance to oxidative stress.[5]

In the Tunisian population, a dramatic increase in the incidence of CAD has been observed, yet the prevalence of sd-LDL and phospholipids (P) has not yet been examined.[6] Indeed, in type 2 diabetes mellitus (T2DM), dyslipidemia-induced insulin resistance is characterized by a relative normal range of LDL and a preponderance of sdLDL particles.[7] Previous methods to fractionate LDL particles have included density-gradient ultracentrifugation, nondenaturing polyacrylamide-gel electrophoresis, high-performance gel-filtration chromatography and nuclear magnetic resonance spectroscopy.[8] However, these methods are unsuitable for clinical practice because they require specialized skills and equipment and they are time consuming. In 2003, Hirano et al[9] reported a simple precipitation method for the direct measurement of sdLDL in serum that involves 2 steps: a manual pretreatment step to precipitate the lipoproteins of density less than 1.044 g per mL using heparin-magnesium, followed by an enzymatic colorimetric measurement of LDL-cholesterol (LDL-C) in the supernatant.[9,10]

Because it was shown[11–14] that phospholipid enrichment of high-density lipoprotein (HDL) particles plays a key role in the HDL purification of cellular cholesterol and in the reverse transport of cholesterol, we evaluated the phospholipid profile in total plasma, non-HDL, and HDL fractions in patients who had coronary problems with and without T2DM for the Tunisian population. Also, we tried to correlate the phospholipids profile to the LDL size estimated by cholesterol content in each LDL subclass.