Ignite Creation Date:
2024-05-06 @ 7:45 AM
Last Modification Date:
2024-10-26 @ 11:52 AM
Study NCT ID:
NCT02593487
Status:
UNKNOWN
Last Update Posted:
2015-11-03
First Post:
2015-10-29
Brief Title:
Effect of Rosuvastatin Therapy on HDL2 Level
Sponsor:
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Organization:
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Study Overview
Official Title:
Effect of Rosuvastatin Therapy on HDL2 Level and Antiatherosclerotic Reverse Cholesterol Transport Process in Chinses CAD Patients With Hyperlipidemia
Status:
UNKNOWN
Status Verified Date:
2015-10
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In many large trials reducing low density lipoprotein LDL levels with rosuvastatin decreased the incidence of major cardiovascular eventsbut little attention to the effects of rosuvastatin on HDL levelespecially 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 HDL2aHDL2b increased
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 HDL2aHDL2b increased
Detailed Description:
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 mgdl In fact a 1 mgdl 0026 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 ie pre β-further distinguished into preβ1- preβ2-preβ3-HDL and a-HDLseparated 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-HDLpreβ2-HDLpreβ3-HDLHDL3HDL213
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 proteinCETP 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 TCtotal 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 ACSacute coronary syndrome patients From articles on Chinese patients with elevate TC or LDL-CHDL-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 CADCAD comorbid with diabeteselevated 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 mgd treatment for 8 weeks could result in a favorable modification of HDL subfraction phenotype Treated with atorvastatin 20mgd 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 maturationfor the step of transformation of HDL3 to HDL2and 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
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 mgdl In fact a 1 mgdl 0026 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 ie pre β-further distinguished into preβ1- preβ2-preβ3-HDL and a-HDLseparated 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-HDLpreβ2-HDLpreβ3-HDLHDL3HDL213
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 proteinCETP 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 TCtotal 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 ACSacute coronary syndrome patients From articles on Chinese patients with elevate TC or LDL-CHDL-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 CADCAD comorbid with diabeteselevated 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 mgd treatment for 8 weeks could result in a favorable modification of HDL subfraction phenotype Treated with atorvastatin 20mgd 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 maturationfor the step of transformation of HDL3 to HDL2and 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None