Research scientists have also demonstrated that HDL has at least three distinct subclasses based on particle size. Different subclasses include nascent HDL, HDL2, and HDL3 with nascent HDL being the smaller and more dense followed by HDL3 and HDL2. One study found gender differences were most pronounced for large HDL, with women having a twofold higher (8 vs. 4 micromole/L) concentration of large HDL particles than men. Additionally, the observed differences in males and females large HDL particle size also decreased with age (Freedman et al., 2004). The authors of a similar study found that the antioxidative activity of large HDL was significantly higher than that of small HDL (Kontush, Chantepie, & Chapman, 2003). Numerous small studies suggest greater predictive power for each of the HDL components including the observation that large HDL particles are more cardioprotective. All subclasses of HDL have been demonstrated to have a role in reverse cholesterol transport, but HDL2 seems to have the most protective effect, with recent evidence suggesting that HDL3 may play a role in LDL oxidation that is just as vital (Yoshikawa, Sakuma, Hibino, Sato, & Fujinami, 1997). Finally HDL seems to have an antioxidant, anti-inflammatory, anti-adhesive, anti-aggregatory, and profibinolytic effect that aids in the control of CAD beyond reverse cholesterol transport mechanisms (Tulenko & Sumner, 2002).

The ATP-III recommended ranges for HDL are low (<40 mg/dL) and high (>60 mg/dL). This is a significant change as previous reports also set recommended levels for HDL, but the low designation was set at less than 35 mg/dL (NIH, 2002). Additionally, the third report has removed specific HDL levels for men and women, and made one recommendation of greater than 50 mg/dL.

Another subclass of lipoprotein is VLDL which can be divided into VLDL1 (large and less dense), VLDL2 (smaller and more dense), and VLDL3 (smallest and most dense). Hypertriglyceridemia is associated with an excess of VLDL1 while hypercholesterolemia is associated with excess VLDL2. VLDL is triglyceride rich and contains C-II, ApoE, and ApoB-100. Lipoprotein lipase reduces the size of VLDL through the release of triglyceride creating a smaller, dense and more cholesterol rich lipoprotein. About two-thirds of VLDL passes down the lipoprotein metabolism cascade terminating as LDL (Tulenka & Sumner, 2002). VLDL1 is a key component is what has been called the atherogenic lipoprotein profile, which when combined with small dense LDL, and low HDL, it is theorized to be a significant lipid risk factor for CAD (Austin et al., 1988). Most triglycerides are consumed from food, but during times of decreased caloric intake, the liver produces triglyceride endogenously (Kwiterovich, 1989). The ATP-III reports that VLDL levels should be less than 31 mg/dL.