LDL ranges in size from the largest and least dense (LDL1), intermediate density and size (LDL2) to the smallest and most dense (LDL3). The ATP-III report states that small LDL particles are formed in large part, although not exclusively, as a response to elevation of triglycerides via the production of very-low density lipoproteins (VLDL) and specifically VLDL1 (Malloy & Kane, 2001; NIH, 2002).

The presence of small, dense LDL particles is associated with more than a three-fold increase in the risk of CAD and is independent of LDL levels (Austin, Breslow, Hennekens, Buring, Willett, & Kraus, 1988). Tulenka & Sumner (2002) further suggest that not all LDL particles are the same and that variations in disease outcomes may by attributable to differences in particle size and number even when LDL levels are the same between patients. The authors of the Physicians Health Study demonstrated that each decrease of eight angstroms in LDL peak particle size was associated with a significant 38% increase in the seven-year risk of myocardial infarction after adjustment for age and smoking status (Lemarche, Lemieux, & Depres, 1999).

The correlation between particle size and CAD may exist because of the physiological properties of smaller particles. Researchers suggests smaller and denser LDL particles are more susceptible to in vitro oxidation and have been shown to be degraded less rapidly (Hsueh & Law, 1998). In addition, smaller particles diffuse more easily into the sub-endothelial space in the periphery. A stronger diffusion gradient would push more particles into the arterial wall, attract more macrophages, and develop more foam cells.

Using gel electrophoresis, previous studies have computed and investigated both LDL peak particle size and the mean LDL particle size (Hsueh & Law, 1998). Mean LDL particle size is determined by computing the relative abundance of each of the LDL subclasses within one individual through a densitometric scan (Hsueh & Law, 1998; Lemarche et al., 1999). The results of these studies have led to the development of two different categories of LDL classification that rely on both peak particle size and LDL subclass distribution (Tulenko & Sumner, 2002). These two designations are Phenotype A and Phenotype B. Phenotype A consists of a predominance of LDL particles of >25.5 nanometers and Phenotype B is defined as the predominance of small LDL particles with diameters However, Cromwell and Otvos (2004) believe it is not clear that small LDL particles are more atherogenic than large ones simply because individuals with small LDL particles also have a higher LDL particle number. The authors further state that LDL particle number measured by nuclear magnetic resonance has consistently been shown to be a strong, independent predictor of CAD. In other words, small dense particles may have been found to be more atherogenic due to a higher number of particles that are typically associated with small dense particles. Also, the combination of the two (high particle number, and small dense particles) may place individuals at more risk than either risk factor alone.