Effect of Rosuvastatin Therapy on HDL2 Level
Effect of Rosuvastatin Therapy on HDL2 Level
In many large trials, reducing low density lipoprotein (LDL) levels with rosuvastatin
 decreased the incidence of major cardiovascular events，but little attention to the effects of
 rosuvastatin on HDL level，especially on HDL subtype.

 Epidemiological evidence strongly favors the notion that the risk of cardiovascular disease
 (CVD) is inversely related to the plasma high-density lipoprotein (HDL) cholesterol
 concentration.

 HDL can be subdivided into large-sized (HDL2a, HDL2b) and small-sized subclasses (preb1-HDL,
 HDL3c, HDL3b, HDL3a) and preb2-HDL. Some studies indicate that only large HDL2a and HDL2b
 particles make HDLs possess anti-atherogenic functions.

 The investigators assume that rosuvastatin could play the role of anti-atherosclerosis though
 the levels of HDL2a、HDL2b increased.
Elevated LDL-C and lowered HDL-C are important risk factors for cardiovascular disease.
 Raising HDL-C is an attractive approach for reducing the residual risk of cardiovascular
 events that persist in many patients receiving low-density LDL-C -lowering therapy with
 statins. From previous studies, it is concluded that compared to atorvastatin, rosuvastatin
 could significantly increase HDL-C levels from baseline. However, which benefits the elevated
 HDL-C will bring to these patients who receive statin lowing LDL-C therapy are still unknown.
 Despite strong evidence that HDL-C levels predict atherosclerotic events, attempts at using
 an HDL-based treatment strategy as a therapeutic target have not yet been successful at the
 present time. However, on the basis of an enormous amount of basic scientific and clinical
 investigation, the International Atherosclerosis Society and US National Lipid Association
 still believe that there are a considerable number of reasons supporting the need to continue
 to investigate the therapeutic effect of modulating HDL structure and function.

 It has long been known that a low level of HDL cholesterol is a powerful independent
 predictor of increased cardiovascular risk, even among patients with LDL cholesterol levels
 below 70 mg/dl. In fact, a 1 mg/dl (0.026 mM) increment in HDL-C levels was associated with a
 significant decrease in the risk of coronary heart disease (CAD) of 2% in men and 3% in
 women. HDL-C has been proposed to have several anti-atherosclerotic properties, including the
 ability to mediate reverse cholesterol transport (RCT), antioxidant capacity,
 anti-inflammatory properties, nitric oxide-promoting activity, and an ability to transport
 proteins with their own intrinsic biological activities. RCT describes the metabolism and an
 important antiatherogenic function of HDL, namely, the HDL-mediated efflux of cholesterol
 from cells of the arterial wall and its subsequent delivery to the liver and steroidogenic
 organs, thus preventing atherosclerosis. HDL particles are responsible for RCT, as critical
 acceptors of cholesterol from lipid-laden macrophages and thereby play an important role in
 the maintenance of net cholesterol balance in the arterial wall and in the reduction of
 pro-inflammatory responses by lipid-rich macrophages. The antiatherogenic properties of HDL
 have been primarily ascribed to RCT. Khera et al. recently reported that HDL efflux capacity
 was inversely and significantly correlated with carotid intima-media thickness (CIMT). A
 one-standard deviation increase in HDL efflux capacity predicted a 30% reduction in the odds
 for CAD. Although cholesterol efflux from macrophages represents only a small portion of
 total RCT, the cholesterol efflux from macrophage foam cells is probably the most relevant
 step with respect to preventing or reversing atherosclerosis. HDL can be separated into two
 major parts, i.e., pre β-(further distinguished into preβ1-, preβ2-,preβ3-HDL) and
 a-HDL(separated into 5 distinct subclasses HDL3c 3b 3a 2a 2b). It has been postulated that
 RCT indeed was the metabolic process that nascent preβ-HDL converted to mature a-HDL,
 following the route of preβ1-HDL→preβ2-HDL→preβ3-HDL→HDL3→HDL2[13].

 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.

 It has been demonstrate that atorvastatin 20 mg/d treatment for 8 weeks could result in a
 favorable modification of HDL subfraction phenotype. Treated with atorvastatin 20mg/d
 significantly increased the cholesterol concentration of large HDL particles and decreased
 the cholesterol concentration of small HDL particles although without changes of serum HDL-C
 level in patients with atherosclerosis. However, there are still lack of evidence on the
 effect of rosuvastatin treatment for HDL maturation(for the step of transformation of HDL3 to
 HDL2)and RCT process in CAD and Chinese patients. It has been demonstrated that Low HDL
 cholesterol is frequently associated with low HDL2b and high HDL cholesterol frequently
 associated with high HDL2b. As the investigators discussed above, compared to atorvastatin,
 rosuvastatin could significantly decrease LDL-C level and increase HDL-C level from baseline.
 So besides the basic effect of lowing LDL-C, it has a strong possibility that rosuvastatin
 therapy on CAD patients with hyperlipidemia could reverse the aberrant HDL maturation process
 via elevating lager HDL2 level, and then restore the RCT process to the normal to prevent
 atherosclerosis.
Inclusion Criteria:

 1. Patients with CAD undergoing quantitative coronary angiography ;

 2. Patients with hyperlipidemia: TG(Triglyceride)>1.6mmol/L and/or TC(total
 cholesterol)>4.6mmol/L, and they didn't take antilipemic agents or steroid hormone at
 least three months before this trial.

 3. Patients between the ages of 30 and 75 years, the functions of liver or kidney are not
 severe.

 Exclusion Criteria:

 1. Thyroid dysfunction, Liver or Biliary Tract Diseases, Acute Myocardial Infarction
 during the last half year, Renal Insufficiency or Kidney Failure and Cerebrovascular
 Trauma;

 2. Drug induce Hyperlipidemia, Familial Hypercholesterolemia;

 3. Having a major trauma , operation with intestines and stomach recently or the disease
 affecting drug absorbed;

 4. Having Anaphylactic Reaction, Mental Disorders and Drinking history.

 5. Taking statin, Nicotinic Acids and other drugs which can influence the level of HDL.