The effect of HDL-C on plaque formation is complex, since HDL particles are highly heterogeneous, and exist as a spectrum of small, intermediate and large particles that differ in lipid and protein content. So the increase in plasma HDL-C does not necessarily reflect an increase in reverse cholesterol transport (RCT). Former studies from cholesteryl ester transfer protein(CETP) modulators and inhibitors such as dalcetrapib have limited efficacy to be still on the way may attributed to their concentration only on raising total HDL-C level and undesirable side effects. Results obtained in some studies, have shown that HDL quality (HDL subpopulations), rather than quantity (total HDL concentration), should be the target of future pharmacological therapies. A number of investigations have reported that, with the increase of plasma LDL-C or the decrease of plasma HDL-C concentrations or elevated TC(total cholesterol), or in some CAD patients with hyperlipidemia, or patients of CAD with diabetes, there was a general shift toward smaller-sized HDL (HDL3), which, in turn, indicates that reverse cholesterol transport might be weakened and HDL maturation might be abnormal. Significantly lower larger-sized HDL-HDL2 in CAD patients with hyperlipidemia compared with control patients, and this inverse relationship between HDL-C, HDL2, and CAD is particularly strong in men with type 2 diabetes mellitus. In type 2 diabetes patients, the difference between HDL2 in the myocardial infarction (MI) and non-MI group persists after adjustment for physical activity, alcohol intake, obesity, duration of diabetes, and glycemic control. Moreover, HDL2 deficiency has also been demonstrated to be a primary alteration in myocardial infarction patients even without other significant risk factors. The tendency that small-sized HDL3b, and HDL3a levels were significantly higher, and the large-sized HDL2a and HDL2b levels were significantly lower were also detected in ACS(acute coronary syndrome) patients. From articles on Chinese patients with elevate TC or LDL-C/HDL-C ratio, there was also a general shift toward smaller-sized HDL particles, which implied that the maturation process of HDL was blocked. Overall, accumulate evidences have demonstrated that in patients with CAD/CAD comorbid with diabetes/elevated TC levels, HDL maturation was hampered in the stage of the transformation of small-sized HDL3 to larger sized HDL2. HDL2 levels have inverse associations with the risk of acute myocardial infarction and thus to be protective factors in ischemic heart disease. It has also demonstrated that patients with high HDL2 level were better protected from atherosclerosis.