Disorders of Lipoprotein Metabolism

Clinical Background

With advancing understanding of the disorders of lipoprotein metabolism and coronary atherosclerosis, it is now recognized that the assessment of LDL and HDL subclass distribution represents an important component of cardiovascular laboratory evaluation.²⁶   LDL-C and HDL-C particles are present in all individuals as heterogeneous populations of particles that can be defined based on differences in density and size.  The various LDL and HDL subclass particles also differ in their physiologic effects on the development of, or protection from, atherosclerosis.  Even with a ‘normal’ cholesterol measurement (by NCEP Guidelines), a predominance of small dense LDL particles increases the risk of coronary artery disease (CAD) three-fold compared to a predominance of large buoyant LDL subclass particles.²⁶
Recognizing this relationship, Krauss and Blanche originally described a clinical classification based on patterns of lipoprotein distribution separated on a gradient gel electrophoresis system as LDL Pattern A, B or I (intermediate or A/B).^27,28  LDL Pattern A describes individuals with a predominance of large buoyant LDL particles.  LDL Pattern B describes individuals with predominantly small dense LDL particles.  LDL Pattern I (intermediate or A/B) includes individuals with LDL particles mostly between the A and B regions or those with multiple LDL peaks.²⁹
As an extension of this clinical classification, the Atherogenic Lipoprotein Profile(ALP) was a term originally coined to describe the clinical characteristics often associated with the small LDL (Pattern B) disorder (small LDL trait), which is often epidemiologically found in association with reduced HDL-C and apoA-I levels, high triglycerides, increased plasma apoB and increased intermediate density lipoproteins.^{27,28, 30}  This combination of lipid abnormalities is frequently associated with postprandial lipemia, an increased susceptibility to lipoprotein oxidative damage, early atherosclerosis and insulin resistance (which may precede the development of type 2 Diabetes Mellitus).  A locus on chromosome #19 has been identified as linked to the small LDL trait.  Four additional gene locations also impact the degree of expression.³¹  Approximately 30-50% of men with CAD express the small LDL trait, as well as almost 50% of their first-generation offspring.³²

Source: http://www.bhlinc.com/cirm.php?chapter=5