调脂治疗的新方法ppt课件

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Slide Source,LipidsOnline,www.lipidsonline.org,Frequency Distribution of Serum Homocysteine in Healthy Men and Women,Frequency %,Serum Homocysteine Concentration (,mol/L), 17.0,Frequency Distribution of Seru,Factors Influencing Serum Homocysteine Levels,Genetic,Cystathionine Synthase Deficiency,5,10 - METHF,1,o,Deficiency,Partial Deficiency - Thermolabile,Nutritional Deficiencies,Folate,B,6,B,12,Factors Influencing Serum Hom,Other Factors,Renal Failure,Hypothyroidism,Drugs,Dilantin,Methotrexate,Niacin,Other FactorsRenal Failure,Plasma Homocysteine and Mortality in CHD Patients,Prospective Evaluation of 587 CHD Patients, Followed for 4.6 Years,Fasting Plasma Homocysteine Measured at Baseline,Strong, Graded Relationship between Homocysteine Levels and All-Cause Mortality,Nygard et al.,N Eng J M,ed. 1997;337:230-236.,Plasma Homocysteine and Mortal,Homocysteine Level (,mol/L),Mortality Ratio,9 - 14.9,15 - 19.9,20,1.9,2.8,4.5,Relation between Plasma Homocysteine Level and Mortality,Nygard et al.,N Eng J M,ed. 1997;337:230-236.,Homocysteine Level (mol/L)Mor,Prospective Case-Cohort Study of CHD Incidence and Homocysteine: ARIC Results,3.3 year follow-up in ARIC population (15,792 subjects), with 232 incident CHD cases compared to 537 reference subjects,tHcy was not associated with CHD incidence after controlling for all CHD risk factors. Folate, B,12,and B,6,levels also not predictive,No genetic determinants (MTHFR, CBS) were associated with CHD,Conclusion: tHcy is not an independent risk factor for CHD,Circulation,1998;98:204,Prospective Case-Cohort Study,Homocysteine, Vitamins and Cardiovascular Disease,Authors suggest that tHcy and CVD relationship can be explained through several possibilities,tHcy is elevated because of the presence of vascular disease,Low levels of folate, B,6,and B,12,could be the primary cause of CHD, and tHcy is a marker.,tHcy is directly causal to atherosclerosis development,tHcy may increase CHD risk other than atherosclerosis thrombosis, inflammation,Circulation,1998;98:196,Homocysteine, Vitamins and Car,Homocysteine, Diet and Cardiovascular Disease: AHA Science Advisory Report,Most, but not all, prospective studies suggest an increased risk of CAD, stroke and peripheral vascular disease with homocysteine levels 15,mol/L.,May be a graded relationship between homocysteine levels 10,mol/L and subsequent total and CHD death.,No clinical trials have been done to evaluate effect of lowering homocysteine.,Do not recommend routine homocysteine screening except in high-risk individuals or cases of premature CHD.,Recommended treatment is folate 1 mg, pyridoxine (B,6,) 2550 mg and B,12,0.5 mg daily.,Circulation,1999;99:178-182,Homocysteine, Diet and Cardiov,Planned Randomized Clinical Trialsof Homocysteine Lowering,VISP (Vitamin Intervention for Stroke Prevention)US,N = 3600 with history of stroke or TIA,TreatmentFolate 2.5 mg/B,6,25 mg vs. folate 0.2 mg/B,6,1 mg,SEARCH (Study of Effectiveness of Additional Reductions in Cholesterol and Homocysteine)UK,N = 12,000 with/without vascular disease,TreatmentFolate 2 mg/B,12,1 mg vs. placebo with/without simvastatin 20 or 80 mg/day,Planned Randomized Clinical Tr,Planned Randomized Clinical Trialsof Homocysteine Lowering,WACS (Womens Antioxidant and Cardiovascular Disease Study)US,N = 8000 women with/without vascular disease,TreatmentFolate 2.5 mg/B,6,50 mg/B,12,1 mg vs. placebo,CHAOS2 UK,N = 4000 with CHD,TreatmentFolate 5 mg vs. placebo,Planned Randomized Clinical Tr,Intracellular Oxidative Defense,Superoxide dismutase neutralizes superoxide anions. It contains zinc and copper.,Glutathione peroxidase catabolizes H,2,O,2,. It contains selenium.,Catalase removes H,2,O,2,from the cell and it contains iron.,Intracellular Oxidative Defens,Extracellular Oxidative Defense,Vitamin E (alphatocopherol) and beta carotene are carried in LDL and HDL, and are natural antioxidants,They protect PUFA oxidation in LDL and cell membranes,Tocopherol radicals, formed in quenching superoxide anions, are regenerated to alphatocopherol by vitamin C,Extracellular Oxidative Defens,Clinical Trials With Antioxidants,PhysiciansHealth Study:(initial report),Beta carotene 50 mg qod333 men with CHD44% reduction in CHD events over 5 years,Physicians Health Study: (final report),No effectBeta carotene on CHD incidence,Finnish Cancer Prevention Study:,29,133 male smokersVitamin E 50 mg. Beta carotene 20 mg. Follow-up 58 years,Results: Vitamin E - No effect on cancer or CHD; increased incidence of hemorrhagic strokeBeta carotene - Increased lung cancer; increased CHD,Clinical Trials With Antioxida,Clinical Trials With Antioxidants,Linxian Cancer Prevention Trial,29,000 males and females,Beta carotene 15 mg + alphatocopherol 30 mg + selenium,Follow-up for 5 years,Reduced cancer mortality but no effect on CHD,Clinical Trials With Antioxida,Nutriceuticals and Cardiovascular Health,Vitamin E,Lipid-soluble antioxidant; prevents lipoprotein oxidation; improves endothelial function (NO production); dose 4001200 units/day,Vitamin C,Water-soluble antioxidant; regenerates vitamin E radicals; improves endothelial function,Coenzyme Q10,Lipid-soluble antioxidant that regenerates vitamin E,Carotenoids,Antioxidants,Beta carotene:,Precursor to vitamin A; clinical trials have not found benefit on CVD,Lycopene:,Found in tomatoes; more potent antioxidant; may reduce CHD events andcancer risk,Nutriceuticals and Cardiovascu,Nutriceuticals and Cardiovascular Health,Flavonoids,Antioxidants,Red wine,(Quercetin),Blueberries,(Vacciniummyrtillus),Antiplatelet effect as well,Licorice root,(Glycyrrhiza glabra),Antiplatelet effect; may cause hypokalemia,L-arginine,Increase endothelial NO synthesis, serving as substrate; oral administration improves endothelial function,Nutriceuticals and Cardiovascu,Indicated Patient Population,The LIPOSORBER,LA-15 System is indicated for the following high risk patient population for whom diet and maximum tolerated combination drug therapy has either been ineffective or not tolerated:,Patients with LDL-C,200 mg/dL with documented CHD, OR ,Patients with LDL-C,300 mg/dL,Indicated Patient PopulationT,The Lipsorber,LA-15 System,P,Membrane,Filter,Plasma Line,Salinometer,Waste Lines,Re-Priming,Solution,Regeneration,Solution,Regeneration,Pump,Plasma Pump,LIPOSORBER LA-15,(LDL Adsorption Columns),Blood Withdrawal Line,SULFLUX FS-05,Plasma Separator,Blood Return Line,Blood Pump,P,P,P,P,Heparin Pump,P,The Lipsorber LA-15 SystemPMe,Advantages of Liposorber,LA-15 System,High selectivity for Apo B containing lipoproteins (LDL, VLDL, Lp(a),Little or no effect on other plasma components such as HDL, albumin or IgG,Automated regenerating system,Disposable system,Advantages of Liposorber LA-1,Theory of LDL-C Lowering by the Liposorber,LA-15 System,Baseline Level on Intensive Diet and Maximum Tolerated Drug Therapy,(Still at High Risk),LIPOSORBER,Treatment,Level on Diet Therapy,Drug Therapy,Diet Therapy,LDL-C Level,Time,Pre-treatment Level,Time Average Level,Post-treatment Level,Theory of LDL-C Lowering by th,Summary of Safety,Low incidence of venous access problems. Only 2.4% of treatments were not completed and only 7.8% of patients discontinued due to venous access problems,Low incidence of adverse events after 4,936 treatments. Hypotension most common adverse reaction with an incidence of 0.8% in 33.8% of patients,After analysis of over 30,000 laboratory evaluations, no clinically significant changes related to LIPOSORBER,therapy,Summary of SafetyLow incidence,Acute Percentage Reductions,Lipid/Lipoprotein,Acute PercentageReduction (%),Total Cholesterol,61 71,LDL-C,73 83,HDL-C,3 14,Lp(a),53 - 76,Triglycerides,47 - 68,Acute Percentage ReductionsLip,Summary of Effectiveness,Selective removal of Apo B containing lipoproteins (Acute LDL-C lowering of 73-83%),Time average LDL lowering 42-56%,Retrospective analysis of cardiovascular events showed at 44% reduction of event rates on LIPOSORBER therapy,Summary of EffectivenessSelect,Long-term Effects of LDL-Apheresis on Cardiac Events,Patients:,64 Patients with Familial Hypercholesterolemia,10 Homozygotes, 54 Heterozygotes,Treatment:,LDL-Apheresis and Medication,Follow-Up:,2.5 Year Observation of Coronary Events Including:,Cardiac Death, Coronary Revascularization, Coronary Angioplasty, Atherectomy, CABG, MI or Cerebrovascular Event,Results:,44% Reduction in Event Rate During 2.5 Year Observation Period When Compared to 5 Year Medication Only Period Prior to LDL-Apheresis Treatment,Gordon et al.,Am J Cardiol,1998; 81:407-411,Long-term Effects of LDL-Apher,Long-term Efficacy of LDL-Apheresis on Coronary Heart Disease in FH,Patients:,Heterozygous FH with CHD,Treatment:,LDL-Apheresis and Medication:(N=43),Medication Only:(N=87),Follow-Up:,6 Years Observation of Coronary Events Including Non-Fatal MI, PTCA, CABG and CHD Death,Mabuchi et al.,Circulation.,1998; 82:1489-1495.,Long-term Efficacy of LDL-Aphe,Kaplan-Meier Curves Showing the Proportion of Patients Without Any Coronary Events:,1,0.9,0.8,0.7,0.6,0.5,0.4,0.3,0.2,0.1,0,1,0,2,3,4,5,6,7,8,9,10,11,Medication,p,= 0.0088,LDL-Apheresis,Years,Proportion of Patients,Without Any Event,Mabuchi et al.,Circulation,1998; 82:1489-1495,Reprinted with permission from Excerpta Medica, Inc.,Kaplan-Meier Curves Showing th,Improvement of Peripheral Artery Endothelial Function by Single LDL-Apheresis,Patients:,Seven Patients with Hypercholesterolemia6 Men, 1 Woman,Treatment:,LDL-Apheresis Using the LIPOSORBER LA-15 System,Evaluation:,Forearm Blood Flow (FBF) Before and After Single LDL-Apheresis While Infusing Acetylcholine (ACH) or Sodium Nitroprusside (SNP),Tamai et al.,Circulation,1997; 95:76-82,Improvement of Peripheral Arte,Improvement of Peripheral Artery Endothelial Function by Single LDL-Apheresis,Responses of Forearm Blood Flow (FBF) to Intra-ArteriallyInfused Acetylcholine (ACh) or Sodium Nitroprusside (SNP),60,50,40,30,20,10,0,0,4,8,ACh (g/min),16,24,FBF (mL/min/100 mL),p,.01,40,30,20,10,0,0,0.2,0.4,NS,0.8,1.2,SNP (g/min),Before Single LDL Apheresis,After Single LDL Apheresis,Tamai et al.,Circulation.,1997; 95:76-82.,Improvement of Peripheral Arte,Improvement of Peripheral Artery Endothelial Function by Single LDL-Apheresis,There Were Significant Correlations Between Ratio of Maximal to Baseline Blood Flow and Levels to Total and Oxidized LDL,Before Single LDL-Apheresis,After Single LDL-Apheresis,10,8,6,4,2,0,40,80,120,Plasma LDL,160,200 (mg/dL),10,8,6,4,2,0,40,80,120,Plasma Oxidized LDL,Ratio of Maximal to Basal,Forearm Blood Flow,Ratio of Maximal to Basal,Forearm Blood Flow,r=-.67,p,.01,160,200 (mg/mL),Tamai et al.,Circulation.,1997; 95:76-82.,Improvement of Peripheral Arte,调脂治疗的新方法ppt课件,20,19,POWERPOINT,SUCCESS,2024/8/24,2019POWERPOINTSUCCESS2023/9/1,20,19,THANK YOU,SUCCESS,2024/8/24,2019THANK YOUSUCCESS2023/9,