[Atherogenicity of low-density lipoproteins (LDL). A problem of quantity or quality?]

The relationship between elevated plasmatic LDL and increased risk of coronary artery disease is definitively established. However the qualitative aspect of the particles also appear to play a significant role: a structural heterogeneity within the LDL particles themselves has been recognized for a number of years. Multiple subclasses have been characterized in several populations of normal and hyperlipidaemic subjects. Some of these subclasses are linked with an atherogenic potential, this is the case for the smaller and the more dense of the particles, defined as the phenotype B. Epidemiological studies have consistently shown an association of this phenotype with an increased risk of coronary artery disease, and various reports have linked it with clinical and angiographic indices of the disease. However, these studies do not allow for causality, and after adjustment for the plasma TG level LDL subclasses distribution is not an independent predictor of coronaropathy anymore. The underlying mechanisms leading to the association are not yet established, but it is possible that small dense LDL are per se atherogenic. Considerable evidence is now available to support some of the hypothesis: denser LDL have a lower affinity for the LDL BE receptor, are more succeptible to oxidative damage, and may have modified interaction with various components of the arterial wall. Moreover several authors have shown that a number of lipid lowering drugs, like fibrates, could normalize to a significant extent the plasma profile of LDL as a result of preferential reduction in the elevated levels of the denser more atherogenic subspecies.