Focus on High Density LipoproteinsFocus on High Density LipoproteinsDr. Sachin Verma MD, FICM, FCCS, ICFCFellowship in Int...
Lipoprotein Classes and AtherosclerosisLipoprotein Classes and AtherosclerosisChylomicrons,Chylomicrons,VLDL, and theirVLD...
IntroductionIntroduction High-density lipoprotein (HDL) is one ofthe five major groups of lipoproteinsthat enables lipids...
Structure of HDLStructure of HDL HDL is the smallest of theHDL is the smallest of thelipoprotein particles.lipoprotein pa...
HDL StructureHDL StructureHDL contains approximatelyHDL contains approximately 55% protein55% protein 3-15% triglyceride...
HDL StructureHDL StructureHDL contains several types ofHDL contains several types ofapolipoproteins including:apolipoprote...
HDL StructureHDL StructureCholesterolacceptorCholesterylesterdonorReverse CholesterolTransport (RCT)Anti-thromboticHDL-CPr...
HDL StructureHDL Structure
HDL StructureHDL Structure
Alpha HDL BuoyancyAlpha HDL Buoyancy
HDL SynthesisHDL Synthesis Synthesis of new high-densitySynthesis of new high-densitylipoprotein (HDL) particles beginsli...
Reverse Cholesterol Transport: Cellular levelReverse Cholesterol Transport: Cellular level
Role of HDL in lipid redistribuionRole of HDL in lipid redistribuionRole of high-density lipoprotein(HDL) in the redistrib...
Reverse Cholesterol Transport: Cellular levelReverse Cholesterol Transport: Cellular levelSeveral steps in the metabolismo...
Reverse Cholesterol Transport: Cellular levelReverse Cholesterol Transport: Cellular levelHigh-density lipoprotein (HDL)ch...
HDL metabolism and reverse cholesterolHDL metabolism and reverse cholesteroltransporttransport
Role of Hepatic Lipase and Lipoprotein LipaseRole of Hepatic Lipase and Lipoprotein Lipasein HDL Metabolismin HDL Metaboli...
HDL Metabolism in CETP DeficiencyHDL Metabolism in CETP DeficiencyA-ICEFCFCLCATA-IMacrophageBDelayed catabolismCETPABC1HDL...
Targeting HDL MetabolismTargeting HDL MetabolismImprove HDL function- apoAI Milano- apoAI mimetic peptidesIncrease HDL syn...
CETP Inhibition and Lipoprotein MetabolismCETP Inhibition and Lipoprotein Metabolism
Cholesterol efflux and reverse cholesterolCholesterol efflux and reverse cholesteroltransport is modulated by two receptor...
HDL-C Protection Against AtherosclerosisHDL-C Protection Against AtherosclerosisActs by inhibitingActs by inhibiting Oxid...
Inhibitory properties of HDLInhibitory properties of HDL
HDL-C: Anti-atherogenic effectsHDL-C: Anti-atherogenic effectsHDL inhibits expression of adhesionmoleculesHDL inhibitsoxid...
HDL metabolism: 5 key genesHDL metabolism: 5 key genes
HDL: Apo AI-rich particlesHDL: Apo AI-rich particles
Anti-inflammatory effects of HDLAnti-inflammatory effects of HDL
Antioxidant Action of HDL cholesterolAntioxidant Action of HDL cholesterol
Antioxidant Action of HDL cholesterolAntioxidant Action of HDL cholesterol
LDLLDLMiyazaki A et al. Biochim Biophys Acta 1992;1126:73-80.EndotheliumVessel LumenMonocyteModified LDLMacrophageMCP-1Adh...
LDLLDLCockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994.EndotheliumVessel LumenMonocyteModified LDLMacro...
LDLLDLEndotheliumVessel LumenMonocyteModified LDLMacrophageMCP-1AdhesionMoleculesCytokinesHDL Inhibits the Oxidative Modif...
Additional Anti-inflammatory Properties of HDLAdditional Anti-inflammatory Properties of HDL HDL bind and neutralizesHDL ...
Apo A-I protects against atherosclerosisApo A-I protects against atherosclerosis
Recommended range of HDLRecommended range of HDLThe American Heart Association, NIH and NCEP provides a set ofThe American...
Relationship between HDL cholesterol and CHD events.Relationship between HDL cholesterol and CHD events.Data from the Fram...
Major cardiovascular event frequency byMajor cardiovascular event frequency byLDL-C and HDL-C levels in TNT studyLDL-C and...
Causes of Low HDLCauses of Low HDL
Steps to Improve HDL LevelSteps to Improve HDL LevelLife style modificationsLife style modifications– ExerciseExercise– Al...
HDL-C levels are modifiable by the quantity andHDL-C levels are modifiable by the quantity andquality of exercisequality o...
HERITAGE STUDY: Effects of 20 wks of endurance exercise trainingHERITAGE STUDY: Effects of 20 wks of endurance exercise tr...
Smoking cessation increases only HDL-C, but not TC,LDL-C or TGSmoking cessation increases only HDL-C, but not TC,LDL-C or TG
Mechanism of action of nicotinic acidMechanism of action of nicotinic acid
Fenofibrate &gemfibrozil arederivatives of fibricacid that lower TGsand increase HDLlevels. Fenofibrate ismore effective a...
Mechanism of Action of FenofibrateMechanism of Action of Fenofibrate
Statin drugs are structural analogs of HMG-CoAStatin drugs are structural analogs of HMG-CoA
Statin Evidence: Landmark Statin TrialsStatin Evidence: Landmark Statin Trials
Statin Evidence: Expanding BenefitsStatin Evidence: Expanding Benefits
Statin Evidence: BenefitsStatin Evidence: Benefits• The statin trials have demonstrated significant decreases in CVDThe st...
Drug ClassDrug Class LDL-CLDL-C HDL-CHDL-C TriglyceridesTriglyceridesStatins*Statins* 18% to 60%18% to 60% 5% to 15%5% to ...
Statin Efficacy: ACCESSStatin Efficacy: ACCESS
DisclaimerDisclaimerThe data, images, graphs and tables provided in this presentation has been developed by clinicians and...
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Focus on high density lipoproteins

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  • HDL is a class of heterogeneous lipoprotein s containing approximately equal amounts of lipid and protein.1 HDL particles are characterized by high density (>1.063 g/mL) and small size (Stoke’s diameter =5 to 17 nm). The various HDL subclasses vary in quantitative and qualitative content of lipids, apo lipoprotein s, enzymes, and lipid transfer proteins, resulting in differences in shape, density, size, charge, and antigenicity. Most of apo lipoprotein A-I (apo A-I), the predominant HDL protein, migrates in agarose gels with -electrophoretic mobility and is designated –LpA-I. This fraction accounts for almost all of the cholesterol quantified in the clinical laboratory as HDL-C. -HDL can be further fractionated by density into HDL2 and HDL3, by size, or by apo lipoprotein composition. Approximately 5% to 15% of apo A-I in human plasma is associated with particles with pre–ß-electrophoretic mobility. These can be further differentiated into pre–ß1-LpA-I, pre–ß2-LpA-I, and pre–ß3-LpA-I particles. These lipid-poor particles are increased in extravascular compartments where reverse cholesterol transport takes place Source: Baylor College of Medicine, Lipids Online (January 29, 2001). "Heterogeneity of HDL". http://www.lipidsonline.org/slides/slide01.cfm?q=apolipoprotein&dpg=59. Retrieved February 20 2006.
  • HDL is a class of heterogeneous lipoprotein s containing approximately equal amounts of lipid and protein.1 HDL particles are characterized by high density (>1.063 g/mL) and small size (Stoke’s diameter =5 to 17 nm). The various HDL subclasses vary in quantitative and qualitative content of lipids, apo lipoprotein s, enzymes, and lipid transfer proteins, resulting in differences in shape, density, size, charge, and antigenicity. Most of apo lipoprotein A-I (apo A-I), the predominant HDL protein, migrates in agarose gels with -electrophoretic mobility and is designated –LpA-I. This fraction accounts for almost all of the cholesterol quantified in the clinical laboratory as HDL-C. -HDL can be further fractionated by density into HDL2 and HDL3, by size, or by apo lipoprotein composition. Approximately 5% to 15% of apo A-I in human plasma is associated with particles with pre–ß-electrophoretic mobility. These can be further differentiated into pre–ß1-LpA-I, pre–ß2-LpA-I, and pre–ß3-LpA-I particles. These lipid-poor particles are increased in extravascular compartments where reverse cholesterol transport takes place Source: Baylor College of Medicine, Lipids Online (January 29, 2001). "Heterogeneity of HDL". http://www.lipidsonline.org/slides/slide01.cfm?q=apolipoprotein&dpg=59. Retrieved February 20 2006.
  • HDL is a class of heterogeneous lipoprotein s containing approximately equal amounts of lipid and protein.1 HDL particles are characterized by high density (>1.063 g/mL) and small size (Stoke’s diameter =5 to 17 nm). The various HDL subclasses vary in quantitative and qualitative content of lipids, apo lipoprotein s, enzymes, and lipid transfer proteins, resulting in differences in shape, density, size, charge, and antigenicity. Most of apo lipoprotein A-I (apo A-I), the predominant HDL protein, migrates in agarose gels with -electrophoretic mobility and is designated –LpA-I. This fraction accounts for almost all of the cholesterol quantified in the clinical laboratory as HDL-C. -HDL can be further fractionated by density into HDL2 and HDL3, by size, or by apo lipoprotein composition. Approximately 5% to 15% of apo A-I in human plasma is associated with particles with pre–ß-electrophoretic mobility. These can be further differentiated into pre–ß1-LpA-I, pre–ß2-LpA-I, and pre–ß3-LpA-I particles. These lipid-poor particles are increased in extravascular compartments where reverse cholesterol transport takes place Source: Baylor College of Medicine, Lipids Online (January 29, 2001). "Heterogeneity of HDL". http://www.lipidsonline.org/slides/slide01.cfm?q=apolipoprotein&dpg=59. Retrieved February 20 2006.
  • HDL is a class of heterogeneous lipoprotein s containing approximately equal amounts of lipid and protein.1 HDL particles are characterized by high density (>1.063 g/mL) and small size (Stoke’s diameter =5 to 17 nm). The various HDL subclasses vary in quantitative and qualitative content of lipids, apo lipoprotein s, enzymes, and lipid transfer proteins, resulting in differences in shape, density, size, charge, and antigenicity. Most of apo lipoprotein A-I (apo A-I), the predominant HDL protein, migrates in agarose gels with -electrophoretic mobility and is designated –LpA-I. This fraction accounts for almost all of the cholesterol quantified in the clinical laboratory as HDL-C. -HDL can be further fractionated by density into HDL2 and HDL3, by size, or by apo lipoprotein composition. Approximately 5% to 15% of apo A-I in human plasma is associated with particles with pre–ß-electrophoretic mobility. These can be further differentiated into pre–ß1-LpA-I, pre–ß2-LpA-I, and pre–ß3-LpA-I particles. These lipid-poor particles are increased in extravascular compartments where reverse cholesterol transport takes place Source: Baylor College of Medicine, Lipids Online (January 29, 2001). "Heterogeneity of HDL". http://www.lipidsonline.org/slides/slide01.cfm?q=apolipoprotein&dpg=59. Retrieved February 20 2006.
  • HDL is a class of heterogeneous lipoprotein s containing approximately equal amounts of lipid and protein.1 HDL particles are characterized by high density (>1.063 g/mL) and small size (Stoke’s diameter =5 to 17 nm). The various HDL subclasses vary in quantitative and qualitative content of lipids, apo lipoprotein s, enzymes, and lipid transfer proteins, resulting in differences in shape, density, size, charge, and antigenicity. Most of apo lipoprotein A-I (apo A-I), the predominant HDL protein, migrates in agarose gels with -electrophoretic mobility and is designated –LpA-I. This fraction accounts for almost all of the cholesterol quantified in the clinical laboratory as HDL-C. -HDL can be further fractionated by density into HDL2 and HDL3, by size, or by apo lipoprotein composition. Approximately 5% to 15% of apo A-I in human plasma is associated with particles with pre–ß-electrophoretic mobility. These can be further differentiated into pre–ß1-LpA-I, pre–ß2-LpA-I, and pre–ß3-LpA-I particles. These lipid-poor particles are increased in extravascular compartments where reverse cholesterol transport takes place Source: Baylor College of Medicine, Lipids Online (January 29, 2001). "Heterogeneity of HDL". http://www.lipidsonline.org/slides/slide01.cfm?q=apolipoprotein&dpg=59. Retrieved February 20 2006.
  • Synthesis of new high-density lipoprotein (HDL) particles begins with the secretion of apolipoprotein A-I (apoA-I) from the liver. Fibrates have been shown to increase the expression of apoA-I in human hepatocytes150, 151. Lipid-free or lipid-poor apoA-I can subsequently serve as an acceptor for ABC transporter A1 (ABCA1)-mediated lipid efflux from hepatocytes or macrophages. Infusion of apoA-I has been shown to attenuate atherosclerosis in animals101 and possibly in humans31. ABCA1-mediated lipid efflux from macrophages can also be enhanced by transcriptional upregulation of this lipid transporter through the nuclear receptors liver X receptor (LXR)/retinoid X receptor (RXR)18 or retinoic acid receptor- (RAR)128. ABCA1-mediated efflux of cholesterol and phospholipids results in the formation of pre- or nascent HDL particles that are further modified by lecithin-cholesterol acyltransferase (LCAT). The resulting HDL2 (larger, less dense particles) and HDL3 (smaller, more dense particles) can serve as acceptors for ABCG1-mediated cholesterol efflux26. Expression of this transporter can also be stimulated by LXR activation152. Infusion of recombinant phospholipid–apoA-I complexes31 and large unilamellar phospholipid vesicles (LUVs)153 have been shown to increase HDL levels, presumably by acting as acceptors for ABCG1-mediated cholesterol efflux. Cholesterol esters from HDL can be transferred to apoB-containing lipoproteins by the action of cholesteryl ester transfer protein (CETP). Inhibition of CETP in humans has recently been shown to increase HDL and lower low-density lipoprotein (LDL) cholesterol84. The catabolism of HDL can also be inhibited by nicotinic acid through a mechanism that is largely unknown. Finally, HDL cholesterol can be taken up by the liver and subsequently secreted into the bile in a process that is mediated by scavenger receptor BI (SR-BI).
  • Several steps in the metabolism of HDL can contribute to the transport of cholesterol from lipid laden macrophages of atherosclerotic arteries, termed foam cells to the liver for secretion into the bile. This pathway has been termed reverse cholesterol transport and is considered as the classical protective function of HDL towards atherosclerosis.
  • Role of high-density lipoprotein (HDL) in the redistribution of lipids from cells with excess cholesterol to cells requiring cholesterol or to the liver for excretion. The reverse cholesterol transport pathway is indicated by arrows (net transfer of cholesterol from cells ➙ HDL ➙ LDL ➙ liver). CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; FC, free cholesterol; HDL-E, HDL with apolipoprotein E; IDL, intermediate-density lipoprotein; LCAT, lecithin:cholesterol acyltransferase; LDL, low-density lipoprotein; LDLR, LDL receptor; PL, phospholipid; SR-BI, class B, type I scavenger receptor; Tg, triglyceride; VLDL, very-low-density lipoprotein.
  • Several steps in the metabolism of HDL can contribute to the transport of cholesterol from lipid laden macrophages of atherosclerotic arteries, termed foam cells to the liver for secretion into the bile. This pathway has been termed reverse cholesterol transport and is considered as the classical protective function of HDL towards atherosclerosis.
  • High-density lipoprotein (HDL) cholesterol promotes and facilitates the process of reverse cholesterol transport (RCT), whereby excess macrophage cholesterol is effluxed to HDL and ultimately returned to the liver for excretion. Efflux to nascent and mature HDL occurs via the transporters ABCA1 and ABCG1, respectively. The HDL cholesterol is returned to the liver via the hepatic receptor SR-BI or by transfer to apolipoprotein (apo) B–containing lipoproteins by the action of cholesteryl ester transfer protein (2).
  • Role of Hepatic Lipase and Lipoprotein Lipase in HDL Metabolism Dietary (exogenous) fat is absorbed into chylomicrons (CMs). In endogenous lipid synthesis, the liver synthesizes triglycerides (TGs) and cholesteryl esters (CEs) and packages them into very-low-density lipoproteins (VLDLs). The enzyme lipoprotein lipase (LPL), bound to the surface of the capillary endothelium (especially in muscle and adipose tissue), hydrolyzes TG in CMs and in VLDLs. Apolipoprotein C-II (apoC-II), found on CMs, is a required cofactor for LPL. The free fatty acids generated from TG hydrolysis are a source of energy or fat storage, and the resulting CM remnant (CMR) is released and is eventually taken up by the liver. VLDL, which contains the major structural protein apoB-100, is hydrolyzed by LPL to form intermediate-density lipoprotein (IDL). Secreted CMs contain apoAs, which are transferred with phospholipids into the high-density lipoprotein (HDL) fraction during lipolysis. Similar HDL particles (HDL 2 ) may be formed as a byproduct of the lipolysis of VLDL. Hepatic lipase, found primarily on the endothelium of the hepatic sinusoids, hydrolyses HDL 2 TG and phospholipids to form small HDL 3 particles, 2 which may be cleared by the kidney.   References: Brunzell JD. Familial lipoprotein lipase deficiency and other causes of the chylomicronemia syndrome. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 7 th ed. New York: McGraw-Hill; 1995:1913–1932. Breslow JL. Familial disorders of high-density lipoprotein metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 7 th ed. New York: McGraw-Hill; 1995:2031–2052. Rader DJ. Lipid disorders. In: Topol EJ, ed. Textbook of Cardiovascular Medicine. Philadelphia: Lippincott-Raven; 1998:59–90.
  • HDL Metabolism in CETP Deficiency Nascent high-density lipoprotein (HDL) picks up cholesterol from cells in the periphery and is then converted into cholesteryl ester (CE)–rich HDL through the action of lecithin:cholesterol acyltransferase (LCAT). In normal lipoprotein metabolism, HDL CE can be transferred to triglyceride-rich lipoproteins through the activity of plasma CE transfer protein (CETP). In subjects with a deficiency of CETP, the conversion of HDL to very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (LDL) is blocked, leading to delayed catabolism of HDL CE, with consequent marked increases in the concentrations of HDL cholesterol and apolipoprotein A-I.   References: Havel RJ, Kane JP. Introduction: structure and metabolism of plasma lipoproteins. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 7 th ed. New York: McGraw-Hill; 1995:1841–1851. Breslow JL. Familial disorders of high-density lipoprotein metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 7 th ed. New York: McGraw-Hill; 1995:2031–2052.
  • HDL carries many lipid and protein species, many of which have very low concentrations but are biologically very active. For example, HDL and their protein and lipid constituents help to inhibit oxidation , inflammation, activation of the endothelium, coagulation or platelet aggregation. All these properties may contribute to the ability of HDL to protect from atherosclerosis, and it is not yet known what is most important.
  • High-density lipoprotein exerts a number of potentially antiatherogenic effects independent of cholesterol efflux and centripetal transport, including inhibiting lipid oxidation, impairing leukocyte adhesion and monocyte activation, promoting nitric oxide (NO) production and flow-induced vasodilation, preventing endothelial cell damage and death, and inhibiting activation of platelets and the coagulation cascade.
  • HDL interacts with a cell membrane protein known as SRB1 which allows the cholesterol ester to be selectively adsorbed into the liver, thereby allowing the HDL particle to return to the blood plasma where it can again absorb cholesterol from other tissues and begin the process of reverse cholesterol transport again. Increased HDL synthesis may result in increased reverse cholesterol transport (RCT) and decrease atherosclerosis.
  • High-density lipoproteins (HDL) have anti-inflammatory effects, which are implicated in its anti-atherogenic properties. Effects on endothelial cells are generally well described. In vitro studies have shown that spherical HDL from human plasma, as well as discoidal reconstituted HDL containing apolipoprotein A-I (apoA-I), inhibit expression of VCAM‑1 and ICAM-1 in endothelial cells and reduce the binding of monocytes to the endothelial surface
  • HDL enhances NO production by eNOS in vascular endothelium. (a) HDL causes membrane-initiated signaling, which stimulates eNOS activity. The eNOS protein is localized in cholesterol-enriched (orange circles) plasma membrane caveolae as a result of the myristoylation and palmitoylation of the protein. Binding of HDL to SR-BI via apoAI causes rapid activation of the nonreceptor tyrosine kinase src, leading to PI3K activation and downstream activation of Akt kinase and MAPK. Akt enhances eNOS activity by phosphorylation, and independent MAPK-mediated processes are additionally required. HDL also causes an increase in intracellular Ca2+ concentration (intracellular Ca2+ store shown in blue; Ca2+ channel shown in pink), which enhances binding of calmodulin (CM) to eNOS. HDL-induced signaling is mediated at least partially by the HDL-associated lysophospholipids SPC, S1P, and LSF acting through the G protein–coupled lysophospholipid receptor S1P3. HDL-associated estradiol (E2) may also activate signaling by binding to plasma membrane–associated estrogen receptors (ERs), which are also G protein coupled. It remains to be determined if signaling events are also directly mediated by SR-BI Reference Yuhanna, IS, et al. High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat. Med. 2001. 7: 853-857. Nofer, J-R, et al. HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3. J. Clin. Invest. 2004. 113: 569-581. Gong, M, et al. HDL-associated estradiol stimulates endothelial NO synthase and vasodilation in an SR-BI-dependent manner. J. Clin. Invest. 2003.
  • HDL regulates eNOS abundance and subcellular distribution. In addition to modulating the acute response, the activation of the PI3K–Akt kinase pathway and MAPK by HDL upregulates eNOS expression (open arrows). HDL also regulates the lipid environment in caveolae (dashed arrows). Oxidized LDL (OxLDL) can serve as a cholesterol acceptor (orange circles), thereby disrupting caveolae and eNOS function. However, in the presence of OxLDL, HDL maintains the total cholesterol content of caveolae by the provision of cholesterol ester (blue circles), resulting in preservation of the eNOS signaling module Reference Ramet, ME, et al. High-density lipoprotein increases the abundance of eNOS protein in human vascular endothelial cells by increasing its half-life. J. Am. Coll. Cardiol. 2003. 41: 2288-2297. Blair, A, Shaul, PW, Yuhanna, IS, Conrad, PA, Smart, EJ. Oxidized low density lipoprotein displaces endothelial nitric-oxide synthase (eNOS) from plasmalemmal caveolae and impairs eNOS activation. J. Biol. Chem. 1999. 274: 32512-32519. Uittenbogaard, A, Shaul, PW, Yuhanna, IS, Blair, A, Smart, EJ. High density lipoprotein prevents oxidized low density lipoprotein-induced inhibition of endothelial nitric-oxide synthase localization and activation in caveolae. J. Biol. Chem. 2000. 275: 11278-11283.
  • HDL prevent formation of foam cells Perhaps the best-known function of HDL is the promotion of cholesterol efflux from cells. Efflux of cholesterol from foam cells leads to a reduction in foam cell formation; although the macrophages may accumulate, they are not converted into foam cells. As a result, the inflammatory process is arrested to a certain extent. Therefore, HDL is anti-inflammatory and also protects against the development of atherosclerosis. Reference: Miyazaki A, Rahim AT, Ohta T, Morino Y, Horiuchi S. High density lipoprotein mediates selective reduction in cholesteryl esters from macrophage foam cells. Biochim Biophys Acta 1992;1126:73-80.
  • Inhibition of adhesion molecules The cytokine-induced expression of adhesion molecules in endothelial cells has been shown in vitro and more recently in vivo to be inhibited by HDL, in a process that potentially blocks a very early inflammatory stage in the development of atherosclerosis. Reference: Cockerill GW, Rye K-A, Gamble JR, Vadas MA, Barter PJ. High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules. Arterioscler Thromb Vasc Biol 1995;15:1987-1994.
  • HDL inhibit the oxidative modification of LDL HDL has protective effects in addition to promoting cholesterol efflux. One of the best known of these is the ability to inhibit the oxidation of LDL. To the extent that LDL oxidation is an important step in the development of the inflammatory process, this property of HDL is clearly anti-inflammatory. Reference: Mackness MI, Abbott C, Arrol S, Durrington PN. The role of high-density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation. Biochem J 1993;294:829-834.
  • Additional anti-inflammatory properties of HDL In addition to HDL's cholesterol efflux properties, antioxidant properties, and ability to inhibit adhesion molecule expression in endothelial cells, over the last 10 to 15 years HDL has been shown to have many other effects, several of which are potentially anti-inflammatory. HDL can bind and neutralize the proinflammatory lipopolysaccharides, and may also neutralize the effects of the acute phase reactant SAA, which when it is released into the blood is transported predominantly bound to HDL. References: Baumberger C, Ulevitch RJ, Dayer JM. Modulation of endotoxic activity of lipopolysaccharide by high-density lipoprotein. Pathobiology 1991;59:378-383. Benditt EP, Eriksen N. Amyloid protein SAA is associated with high density lipoprotein from human serum. Proc Natl Acad Sci U S A 1977;74:4025-4028.
  • http://www.med.umich.edu/mdrtc/cores/ChemCore/lipids.htm Lipid Measurement Fact Sheet
  • HDL-C Is a Modifier of Risk at All Levels of LDL-C: the Framingham Study. Though 34% of patients with premature heart disease have LDL-C levels greater than 160 mg/dL, over half of patients (57%) with premature heart disease have low HDL-C levels. 1 The Framingham heart study demonstrated that there was a statistically significant increase in the number of cardiovascular (CV) events in patients with low HDL-C (<34 mg/dL), especially in women ( P <.01). 2,3 As HDL-C decreases, it contributes significantly to CHD risk at all levels of LDL-C. 4 As shown in the patient scenarios on the left side of slide, if all patients have near optimal levels of LDL-C (100 mg/dL), the lower the HDL-C level, the higher the risk of CHD. Also note that in a patient with an LDL-C of 220 mg/dL and an HDL-C level of 45 mg/dL, the risk of CHD is equivalent (1.2) compared with a patient with optimal LDL-C and low HDL-C (1.2). Although these findings raise the possibility that interventions that increase HDL-C might lead to a decrease in the risk of developing CHD, other studies have demonstrated that high HDL-C does not preclude the risk of developing CHD if LDL-C remains elevated. References 1. Genest JJ, et al. Am J Cardiol. 1991;67:1185-1189. 2. Kannel WB, et al. Am J Cardiol. 1983;52:9B-12B. 3. Wilson PWF, et al. Circulation. 1998;97:1837-1847. 4. Castelli WP. Can J Cardiol . 1988;4(suppl A):5A-10A.
  • Analyses have also showed that HDL cholesterol is independently associated with risk for cardiovascular events in statin-treated patients independent of LDL cholesterol levels (Fig 4). Furthermore, the increase in HDL cholesterol associated with simvastatin treatment in the 4S study was predictive of benefit independent of the reduction in LDL cholesterol levels.  A similar result was observed in the Lipid Research Clinics Primary Prevention Trial in which cholestyramine was used as the active agent. In this study a reduction in CHD events correlated positively with changes in LDL cholesterol levels and negatively with changes in HDL cholesterol. For every 1% increase in the concentration of HDL cholesterol there was a 0.6% reduction in CHD events that was independent of the changes in LDL cholesterol levels. References 1. Barter P, Gotto AM, LaRosa JC et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events.  N Engl J Med. 2007;357:1301-10. 2. Pedersen TR, Olsson AG, Faergeman O et al . Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation 1998;97:1453-60. 3. The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984;251:351-64.
  • Source: 1. Jocelyne R. Benatar, Ralph A. Stewar, New Zealand Medical Journal , Vol. 120, No. 2261, Sept. 7, 2007 2. Chapman M, Assmann G, Fruchart J, Shepherd J, Sirtori C. Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid - a position paper developed by the European Consensus Panel on HDL-C . Cur Med Res Opin. 2004 Aug;20(8):1253-68.
  • King A.C et al. Circulation.1995;91:2596-2604.
  • Couillard et al . Arteriscler Thromb Vasc Biol.2004;21:1226-1232.
  • Maeda K et al. Prev Med.2003;37:283-290.
  • HDL inhibit endothelial cell sphingosine kinase The sphingomyelin pathway has been shown to be involved in the mechanism by which TNF-α stimulates the expression of adhesion molecules in endothelial cells. TNF-α activates sphingomyelinase, which begins the sphingomyelin pathway through ceramide, sphingosine, sphingosine 1-phosphate, and then to the nuclear transcription factor NK-κB and ultimately to the expression of a variety of adhesion proteins. In a recently reported study, HDL has been shown to inhibit sphingosine kinase, which catalyzes the sphingosine-to–sphingosine 1-phosphate step. This is at least one of the mechanisms by which HDL inhibits adhesion molecule expression. Reference: Xia P, Vadas MA, Rye KA, Barter PJ, Gamble JR. High density lipoproteins (HDL) interrupt the sphingosine kinase signaling pathway: a possible mechanism for protection against atherosclerosis by HDL. J Biol Chem 1999;274:33143-33147.
  • A number of long-term clinical endpoint studies 1 with statins have demonstrated conclusively that lowering serum cholesterol is associated with significant reductions in cardiovascular morbidity and mortality, both in subjects with established CHD (eg, 4S, 2 CARE, 3 LIPID, 4 ) and in individuals at risk for cardiovascular disease (CVD) (eg, WOSCOPS, 5 AFCAPS/TexCAPS, 6 HPS, 5 ASCOT-LLA 7 ). In the large statin trials, there is an approximate linear relation between CHD event rates and the LDL-C levels on treatment with either statin or placebo. The lowest event rate is in the CARE pravastatin group, which achieved a mean LDL-C of less than 95 mg/dL (2.5 mmol/L). 3 This supports the NCEP recommendation for an LDL-C target of less than 100 mg/dL (2.6 mmol/L) in secondary prevention. 8 1 Kastelein JP. Atherosclerosis. 1999;143(suppl 1):S17-S21. 2 4S Group . Lancet . 1994;344:1383-1389. 3 Sacks FM, et al. Circulation. 1998;97:1446-1452. 4 LIPID Group. N Engl J Med . 1998;339:1349-1357. 5 WOSCOPS Group. Circulation . 1998;97:1440-1445. 6 Downs JR, et al. JAMA . 1998;279:1615-1622. 7 Sever PS, et al. Lancet . 2003;361:1149-1158. 8 NCEP Expert Panel. JAMA. 2001;285:2486-2497.
  • In the 1990s, the WOSCOPS, 1 AFCAPS/TexCAPS, 2 4S, 3 CARE, 4 and LIPID 5 studies demonstrated that long-term intervention with statin therapy reduces mortality and recurrent ischemic cardiovascular events both in individuals at risk for CVD and patients with stable CHD. Since this time, several trials have illustrated the benefits of statin therapy in a variety of other patient populations. The MIRACL study 6 was a 16-week, multicenter, randomized, double-blind, placebo-controlled trial that showed that intensive lowering of LDL-C with atorvastatin (80 mg/day), initiated 24-96 hours after an ACS, reduced the composite endpoint of death, nonfatal myocardial infarction (MI), resuscitated cardiac arrest, or recurrent symptomatic MI requiring emergency rehospitalization from 17.4% to 14.8% ( P = .048) within 16 weeks of treatment. HPS 7 demonstrated that, regardless of baseline LDL-C, simvastatin 40 mg/day significantly decreased the relative risk of major vascular events by 24% among patients considered to be at substantial 5-year risk of death from CHD, including patients with established CHD (primary prevention) and patients with diabetes or treated for hypertension (secondary prevention) . Moreover, there was n o lower LDL-C limit at which benefits of statin therapy were not observed. ASCOT-LLA 8 showed atorvastatin 10 mg significantly lowered the primary endpoint of nonfatal MI (including silent MI) and fatal CHD by 36% in a population of hypertensive patients who were only at moderate cardiovascular risk, and who would not conventionally be deemed dyslipidemic. The reductions in major cardiovascular events with atorvastatin emerged earlier than in many other statin trials. 1 WOSCOPS Group. Circulation . 1998;97:1440-1445. 2 Downs JR, et al. JAMA . 1998;279:1615-1622. 3 4S Group. Lancet . 1994;344:1383-1389. 4 Sacks FM, et al. Circulation . 1998;97:1446-1452. 5 LIPID Group. N Engl J Med . 1998;339:1349-1357. 6 Schwartz GG, et al. JAMA . 2001;285:1711-1718. 7 Heart Protection Study Collaborative Group. Lancet . 2002 ;360:7-22 . 8 Sever PS, et al. Lancet . 2003;361:1149-1158.
  • The “ landmark ” statin trials, including CARE, 1 LIPID, 2 4S, 3 AFCAPS/TexCAPS 4 , and WOSCOPS 5 , have shown that effective lipid-lowering therapy significantly decreases morbidity and mortality from cardiovascular disease across a broad range of patients. In addition to the reduction in CHD events shown in patients with stable coronary disease, the MIRACL trial 6 demonstrated that intensive lowering of LDL-C with atorvastatin (80 mg/day), initiated 24-96 hours after an ACS, reduced the composite endpoint of death, nonfatal MI, resuscitated cardiac arrest, or recurrent symptomatic myocardial ischemia requiring emergency rehospitalization, from 17.4% to 14.8% ( P = .048). Recent data from the HPS 7 and ASCOT-LLA 8 suggest that lowering LDL-C has beneficial effects in patients with normal or moderately elevated LDL-C, and reduces the risk of major coronary events. Data from these studies indicate that all patients at high risk of CHD, including hypertensives, 8 should be considered for statin therapy, regardless of baseline LDL-C concentrations. 1 Sacks FM, et al. Circulation. 1998;97:1446-1452. 2 LIPID Group. N Engl J Med . 1998;339:1349-1357. 3 4S Group . Lancet . 1994;344:1383-1389. 4 Downs JR, et al. JAMA . 1998;279:1615-1622. 5 WOSCOPS Group. Circulation. 1998;97:1440-1445. 6 Schwartz GG, et al. JAMA. 2001;285:1711-1718. 7 Heart Protection Study Collaborative Group. Lancet. 2002 ;360:7-22 . 8 Sever PS, et al. Lancet . 2003;361:1149-1158.
  • This table summarizes the ability of all major lipid-lowering drug classes to impact LDL-C, HDL-C, and triglycerides. Statins clearly dominate in terms of effectiveness at reducing TC and LDL-C. 1,2 1 NCEP Expert Panel. JAMA. 2001;285:2486-2497. 2 Jones PH et al, for the STELLAR Study Group. Am J Cardiol 2003;92:152-160.
  • In the ACCESS study, treatment with atorvastatin (10 to 80 mg) yielded the highest proportion of patients reaching NCEP LDL-C goals (76.3% vs 34.2-57.9%; P <.01). 1 Andrews TC, et al. Am J Med . 2001;111:185-191.
  • Focus on high density lipoproteins

    1. 1. Focus on High Density LipoproteinsFocus on High Density LipoproteinsDr. Sachin Verma MD, FICM, FCCS, ICFCFellowship in Intensive Care MedicineInfection Control Fellows CourseConsultant Internal Medicine and Critical CareIvy Hospital Sector 71 MohaliWeb:- http://www.medicinedoctorinchandigarh.comMob:- +91-7508677495
    2. 2. Lipoprotein Classes and AtherosclerosisLipoprotein Classes and AtherosclerosisChylomicrons,Chylomicrons,VLDL, and theirVLDL, and theircatabolic remnantscatabolic remnantsLDLLDL HDLHDLPro-atherogenicPro-atherogenic Anti-atherogenicAnti-atherogenic
    3. 3. IntroductionIntroduction High-density lipoprotein (HDL) is one ofthe five major groups of lipoproteinsthat enables lipids like cholesterol andtriglycerides to be transported within thewater based blood stream. HDL can remove cholesterol fromatheroma within arteries and transport itback to the liver for excretion or re-utilization. Therefore HDL is also calledas good cholesterol.
    4. 4. Structure of HDLStructure of HDL HDL is the smallest of theHDL is the smallest of thelipoprotein particles.lipoprotein particles. HDL particles have a size of 6-HDL particles have a size of 6-12.5 nanometers12.5 nanometers They have high density ~1.12They have high density ~1.12mainly because of highmainly because of highproportion of proteinsproportion of proteins
    5. 5. HDL StructureHDL StructureHDL contains approximatelyHDL contains approximately 55% protein55% protein 3-15% triglycerides3-15% triglycerides 26-46% phospholipids26-46% phospholipids 15-30% cholesteryl esters15-30% cholesteryl esters 2-10% cholesterol.2-10% cholesterol.
    6. 6. HDL StructureHDL StructureHDL contains several types ofHDL contains several types ofapolipoproteins including:apolipoproteins including: apo-AIapo-AI Apo-AIIApo-AII apo-CIapo-CI apo-CIIapo-CII apo-Dapo-D apo-E.apo-E. Their most abundant apolipoproteins areTheir most abundant apolipoproteins areapo A-I and apo A-II.apo A-I and apo A-II.
    7. 7. HDL StructureHDL StructureCholesterolacceptorCholesterylesterdonorReverse CholesterolTransport (RCT)Anti-thromboticHDL-CProtection againstoxidationModulation ofendothelial functionProtection of the vessel wallEndothelial repairAnti-inflammatory
    8. 8. HDL StructureHDL Structure
    9. 9. HDL StructureHDL Structure
    10. 10. Alpha HDL BuoyancyAlpha HDL Buoyancy
    11. 11. HDL SynthesisHDL Synthesis Synthesis of new high-densitySynthesis of new high-densitylipoprotein (HDL) particles beginslipoprotein (HDL) particles beginswith the secretion ofwith the secretion ofapolipoprotein A-I (apo A-I) fromapolipoprotein A-I (apo A-I) fromthe liver.the liver. The resulting HDL2 (larger, lessThe resulting HDL2 (larger, lessdense particles) and HDL3dense particles) and HDL3(smaller, more dense particles) can(smaller, more dense particles) canserve as acceptors for ABCG1-serve as acceptors for ABCG1-mediated cholesterol efflux26.mediated cholesterol efflux26.
    12. 12. Reverse Cholesterol Transport: Cellular levelReverse Cholesterol Transport: Cellular level
    13. 13. Role of HDL in lipid redistribuionRole of HDL in lipid redistribuionRole of high-density lipoprotein(HDL) in the redistribution oflipids from cells with excesscholesterol to cells requiringcholesterol or to the liver forexcretion. The reversecholesterol transport pathway isindicated by arrows (nettransfer of cholesterol from cellsHDL LDL liver).➙ ➙ ➙
    14. 14. Reverse Cholesterol Transport: Cellular levelReverse Cholesterol Transport: Cellular levelSeveral steps in the metabolismof HDL can contribute to thetransport of cholesterol fromlipid laden macrophages ofatherosclerotic arteries, termedfoam cells to the liver forsecretion into the bile. Thispathway has been termedreverse cholesterol transportand is considered as theclassical protective function ofHDL towards atherosclerosis.
    15. 15. Reverse Cholesterol Transport: Cellular levelReverse Cholesterol Transport: Cellular levelHigh-density lipoprotein (HDL)cholesterol promotes and facilitatesthe process of reverse cholesteroltransport (RCT), whereby excessmacrophage cholesterol is effluxed toHDL and ultimately returned to theliver for excretion. Efflux to nascentand mature HDL occurs via thetransporters ABCA1 and ABCG1,respectively. The HDL cholesterol isreturned to the liver via the hepaticreceptor SR-BI or by transfer toapolipoprotein (apo) B–containinglipoproteins by the action ofcholesteryl ester transfer protein (2).
    16. 16. HDL metabolism and reverse cholesterolHDL metabolism and reverse cholesteroltransporttransport
    17. 17. Role of Hepatic Lipase and Lipoprotein LipaseRole of Hepatic Lipase and Lipoprotein Lipasein HDL Metabolismin HDL MetabolismCM = chylomicron; CMR = chylomicron remnant; HDL =high-density lipoprotein; HL = hepatic lipase; IDL =intermediate-density lipoprotein; LPL = lipoprotein lipase;PL = phospholipase; TG = triglycerideBKidneyEndotheliumBTGCMR/IDLC-IICM/VLDLHLLPLA-ICETGHDL2PLA-ICEHDL3PLPhospholipids andapolipoproteins
    18. 18. HDL Metabolism in CETP DeficiencyHDL Metabolism in CETP DeficiencyA-ICEFCFCLCATA-IMacrophageBDelayed catabolismCETPABC1HDLVLDL/LDLNascent HDLCE
    19. 19. Targeting HDL MetabolismTargeting HDL MetabolismImprove HDL function- apoAI Milano- apoAI mimetic peptidesIncrease HDL synth.or infuse rHDL- apoM? ETC216- LPL LUV’s- apoAI Delipidated HDLExtend/reduce circulationTime Block clearance- trimeric apoAI- SR-BIModulate PL- phosphatidyl inositol- sPLA2Improve lipidationmaturation- ABCA1- ABCG1- LCATHDL remodeling- HL, EL, PLTP?- apoCI?- CETPPL,FC,CE,apo’sPL,FC,CE,apo’sRenal clearance
    20. 20. CETP Inhibition and Lipoprotein MetabolismCETP Inhibition and Lipoprotein Metabolism
    21. 21. Cholesterol efflux and reverse cholesterolCholesterol efflux and reverse cholesteroltransport is modulated by two receptorstransport is modulated by two receptors
    22. 22. HDL-C Protection Against AtherosclerosisHDL-C Protection Against AtherosclerosisActs by inhibitingActs by inhibiting OxidationOxidation InflammationInflammation Activation of endotheliumActivation of endothelium CoagulationCoagulation Platelet aggregationPlatelet aggregation
    23. 23. Inhibitory properties of HDLInhibitory properties of HDL
    24. 24. HDL-C: Anti-atherogenic effectsHDL-C: Anti-atherogenic effectsHDL inhibits expression of adhesionmoleculesHDL inhibitsoxidationof LDLHDL promotescholesteroleffluxHDLactivateseNOSLDLLDLEndotheliumVessel LumenMonocyteModified LDLMacrophageMCP-1AdhesionMoleculesCytokinesIntimaFoamCellNONONONORCT
    25. 25. HDL metabolism: 5 key genesHDL metabolism: 5 key genes
    26. 26. HDL: Apo AI-rich particlesHDL: Apo AI-rich particles
    27. 27. Anti-inflammatory effects of HDLAnti-inflammatory effects of HDL
    28. 28. Antioxidant Action of HDL cholesterolAntioxidant Action of HDL cholesterol
    29. 29. Antioxidant Action of HDL cholesterolAntioxidant Action of HDL cholesterol
    30. 30. LDLLDLMiyazaki A et al. Biochim Biophys Acta 1992;1126:73-80.EndotheliumVessel LumenMonocyteModified LDLMacrophageMCP-1AdhesionMoleculesCytokinesHDL Prevents Formation of Foam CellsHDL Prevents Formation of Foam CellsIntimaHDL Promote Cholesterol EffluxFoamCell
    31. 31. LDLLDLCockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994.EndotheliumVessel LumenMonocyteModified LDLMacrophageMCP-1AdhesionMoleculesCytokinesInhibition of Adhesion MoleculesInhibition of Adhesion MoleculesIntimaHDL InhibitOxidationof LDLHDL Inhibit Adhesion Molecule ExpressionFoamCellHDL Promote CholesterolEfflux
    32. 32. LDLLDLEndotheliumVessel LumenMonocyteModified LDLMacrophageMCP-1AdhesionMoleculesCytokinesHDL Inhibits the Oxidative Modification of LDLHDL Inhibits the Oxidative Modification of LDLFoamCellHDL Promote CholesterolEffluxIntimaHDLInhibitOxidationof LDL
    33. 33. Additional Anti-inflammatory Properties of HDLAdditional Anti-inflammatory Properties of HDL HDL bind and neutralizesHDL bind and neutralizesproinflammatoryproinflammatorylipopolysaccharideslipopolysaccharides The acute phase reactantThe acute phase reactantSAA binds to plasmaSAA binds to plasmaHDL, which possiblyHDL, which possiblyneutralizes the effects ofneutralizes the effects ofSAASAA1. Baumberger C et al. Pathobiology 1991;59:378-383. 2. Benditt EP et al. Proc Natl Acad Sci U S A 1977;74:4025-4028
    34. 34. Apo A-I protects against atherosclerosisApo A-I protects against atherosclerosis
    35. 35. Recommended range of HDLRecommended range of HDLThe American Heart Association, NIH and NCEP provides a set ofThe American Heart Association, NIH and NCEP provides a set ofguidelines for fasting HDL levelsguidelines for fasting HDL levelsLevel mg/dLLevel mg/dL Level mmol/LLevel mmol/L InterpretationInterpretation<40 for men, <50 for<40 for men, <50 forwomenwomen<1.03<1.03 Low HDL cholesterol,Low HDL cholesterol,heightened risk for heart diseaseheightened risk for heart disease40–5940–59 1.03–1.551.03–1.55 Medium HDL levelMedium HDL level>60>60 >1.55>1.55 High HDL level, optimalHigh HDL level, optimalcondition considered protectivecondition considered protectiveagainst heart diseaseagainst heart disease
    36. 36. Relationship between HDL cholesterol and CHD events.Relationship between HDL cholesterol and CHD events.Data from the Framingham StudyData from the Framingham StudyRiskofCHDCastelli WP. Can J Cardiol. 1988;4(suppl A):5A-10A.3214Equivalent Risk
    37. 37. Major cardiovascular event frequency byMajor cardiovascular event frequency byLDL-C and HDL-C levels in TNT studyLDL-C and HDL-C levels in TNT study
    38. 38. Causes of Low HDLCauses of Low HDL
    39. 39. Steps to Improve HDL LevelSteps to Improve HDL LevelLife style modificationsLife style modifications– ExerciseExercise– AlcoholAlcohol– Smoking cessationSmoking cessationDrugsDrugs– NiacinNiacin– FibratesFibrates– StatinsStatins– CETP inhibitorsCETP inhibitors– ApoA-1 Milano/ApoA-1mimeticApoA-1 Milano/ApoA-1mimetic
    40. 40. HDL-C levels are modifiable by the quantity andHDL-C levels are modifiable by the quantity andquality of exercisequality of exercise
    41. 41. HERITAGE STUDY: Effects of 20 wks of endurance exercise trainingHERITAGE STUDY: Effects of 20 wks of endurance exercise trainingon lipid profileon lipid profile
    42. 42. Smoking cessation increases only HDL-C, but not TC,LDL-C or TGSmoking cessation increases only HDL-C, but not TC,LDL-C or TG
    43. 43. Mechanism of action of nicotinic acidMechanism of action of nicotinic acid
    44. 44. Fenofibrate &gemfibrozil arederivatives of fibricacid that lower TGsand increase HDLlevels. Fenofibrate ismore effective atlowering LDL &TGs.FibratesFibrates
    45. 45. Mechanism of Action of FenofibrateMechanism of Action of Fenofibrate
    46. 46. Statin drugs are structural analogs of HMG-CoAStatin drugs are structural analogs of HMG-CoA
    47. 47. Statin Evidence: Landmark Statin TrialsStatin Evidence: Landmark Statin Trials
    48. 48. Statin Evidence: Expanding BenefitsStatin Evidence: Expanding Benefits
    49. 49. Statin Evidence: BenefitsStatin Evidence: Benefits• The statin trials have demonstrated significant decreases in CVDThe statin trials have demonstrated significant decreases in CVDmorbidity and mortality.morbidity and mortality.• Reduction in CVD events has been demonstrated in patientsReduction in CVD events has been demonstrated in patientswith stable CHD as well as acute coronary syndrome patients.with stable CHD as well as acute coronary syndrome patients.• Additionally, lowering LDL-C to target levels has beneficialAdditionally, lowering LDL-C to target levels has beneficialeffects in patients with normal or moderately elevated LDL-C.effects in patients with normal or moderately elevated LDL-C.
    50. 50. Drug ClassDrug Class LDL-CLDL-C HDL-CHDL-C TriglyceridesTriglyceridesStatins*Statins* 18% to 60%18% to 60% 5% to 15%5% to 15% 7% to 37%7% to 37%Bile AcidBile Acid 15% to 30%15% to 30% 3% to 5%3% to 5% No change orNo change orSequestrantsSequestrants increaseincreaseNicotinic AcidNicotinic Acid 5% to 25%5% to 25% 15% to 35%15% to 35% 20% to 50%20% to 50%Fibric AcidsFibric Acids 5% to 20%5% to 20% 10% to 20%10% to 20% 20% to 50%20% to 50%Statin Efficacy: Lipid LoweringStatin Efficacy: Lipid LoweringAdapted from NCEP Expert Panel. JAMA. 2001;285:2486-2497.vvvvvvvvvvv
    51. 51. Statin Efficacy: ACCESSStatin Efficacy: ACCESS
    52. 52. DisclaimerDisclaimerThe data, images, graphs and tables provided in this presentation has been developed by clinicians andThe data, images, graphs and tables provided in this presentation has been developed by clinicians andmedical writers. It has also been validated by experts. Although great care has been taken in compilingmedical writers. It has also been validated by experts. Although great care has been taken in compilingchecking the information, the authors, BioQuest and its servants or agents, and sponsors shall not bechecking the information, the authors, BioQuest and its servants or agents, and sponsors shall not beresponsible or in anyway, liable for any errors, omissions on inaccuracies in the publication whether arisingresponsible or in anyway, liable for any errors, omissions on inaccuracies in the publication whether arisingfrom negligence or otherwise however, or for any consequences arising there from. The inclusion or exclusionfrom negligence or otherwise however, or for any consequences arising there from. The inclusion or exclusionof any product does not mean that the publisher advocates or rejects its use either generally or in anyof any product does not mean that the publisher advocates or rejects its use either generally or in anyparticular field or fields.particular field or fields.The data, images and illustrations are provided in their original form. Wherever applicable, the relevantThe data, images and illustrations are provided in their original form. Wherever applicable, the relevantsources and the details of the original copyright owners are provided for the reference of the readers. Shouldsources and the details of the original copyright owners are provided for the reference of the readers. Shouldyou wish to recreate the data, images, graphs and tables, you are advised to contact the respective authors oryou wish to recreate the data, images, graphs and tables, you are advised to contact the respective authors orservice providers wherever necessary. USV or BioQuest will not be liable for any consequences arising fromservice providers wherever necessary. USV or BioQuest will not be liable for any consequences arising fromthe unauthorized usage of this data.the unauthorized usage of this data.
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