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Welcome to You All

Welcome to You All. Dyslipidemias Dx. and Rx. Dr.Sarma RVS N, M.D., M.Sc (Canada) Consultant in Medicine and Chest, President IMA – Tiruvallur Branch # 3, Jayanagar, Tiruvallur – 602 001 +91 98940 60593, (411 6) 260593. CD ROM Available. The contents of today’s presentation

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Welcome to You All

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  1. Welcome to You All Dr.Sarma@works

  2. Dyslipidemias Dx. and Rx. Dr.Sarma RVSN, M.D., M.Sc (Canada) Consultant in Medicine and Chest, President IMA – Tiruvallur Branch # 3, Jayanagar, Tiruvallur – 602 001 +91 98940 60593, (4116) 260593 Dr.Sarma@works

  3. CD ROM Available The contents of today’s presentation are available in a CD-ROM format for computer and VCD player use. This CD, in addition, contains our talks on ECG, Asthma, COPD, Hypertension Rx. also Dr.Sarma@works

  4. Adult Treatment Panel III (ATP III) Guidelines -2002Updated October 2004 National Cholesterol Education Program - NCEP Dr.Sarma@works

  5. Guidelines that aren’t implemented never work Dr.Sarma@works

  6. CHD Risk Factors ranking - PROCAM Study Smoking 2.3 0.001 LDL cholesterol (mg%) > 100 but < 160 1.9 0.01 > 160 4.3 0.001 Hypertension (SBP > 140; DBP > 90) 1.8 0.001 HDL cholesterol (mg%) 40 to 55 1.7 0.01 < 40 2.7 0.001 Triglycerides (mg%) 105- 167 1.6 0.01 >167 2.6 0.001 Fasting blood glucose (mg%) 110 - 126 1.4 0.05 > 126 1.9 0.01 Family history of MI 1.4 0.05 Risk factor Relative risk P Value

  7. Emerging Risk Factors • Lipoprotein (a) • Homocysteine • Prothrombotic factors • Pro-inflammatory factors • Metabolic syndrome • Sub-clinical atherosclerosis Dr.Sarma@works

  8. CHD Risk Equivalents • Diabetes Mellitus • Peripheral Vascular Disease • > 20% in Framingham risk score • Carotid atheroma • Reno-vascular Disease All forms of AVD Dr.Sarma@works

  9. AVD – Clinical Manifestations For every thing the common denominator is ED Dr.Sarma@works

  10. Progression of Atherosclerosis Dr.Sarma@works

  11. Lipid Peroxidation LDL, IDL Not normally taken up by the vessel wall ROS – Free radicals and Pro-oxidants Freely enters the vessel wall Oxidized LDL, IDL Macrophages Endothelium Scavenger pathway Foam Cells Cytokines, GF Atherosclerosis Dr.Sarma@works

  12. The Havoc by LDL at the endothelium Vessel Lumen Monocyte LDL AdhesionMolecules Endothelium MCP-1 LDL Intima Modified LDL Cytokines Growth FactorsMetalloproteinases Cell ProliferationMatrix Degradation Macrophage Foam Cell Ross R. N Engl J Med 1999;340:115-126.

  13. Vulnerable Atherosclerotic Plaque Non-Vulnerable Atherosclerotic Plaque Pathogenesis of ACS

  14. Plaque Rupture with Thrombus

  15. TG EC Apoprotein boat Lipid Transport Apo A I and A II for HDLApo B100 for LDL, Lp(a) Apo B100+C+E – VLDL, IDLApo B48+C+A+E – Chy. microns Dr.Sarma@works

  16. HDL A I, A II B 100 TG TG C TG TG C C B 48+E+C CM B 100 + E +C Lipoproteins LDL VLDL Dr.Sarma@works

  17. Cholesterols and Apoproteins • Total Cholesterol < 200 Apoprotein • ‘Bad’ CholesterolsApo B type • LDLc, IDLc < 100 B100 or B100 +E • VLDLc, VLDLr < 30 B100 + E + C • Lp(a), small LDL < 20 B100 + (a) • ‘Good’ Cholesterols Apo A type • HDL 1, HDL 2, HDL 3 > 50 A I and A II HDL 1 and HDL 2 are protective Dr.Sarma@works

  18. Chylomicrons << 1.006 VLDL < 1.006 IDL < 1.019 LDL Small LDL HDL < 1.063 < 1.085 < 1.210 Particle size & Density Atherogenicity increases as density increases Dr.Sarma@works

  19. Atherogenic Particles Apolipoprotein B Measurements Non-HDL-C VLDL VLDLR IDL LDL SDL TG-rich lipoproteins Dr.Sarma@works

  20. Two Types of Lipids Dr.Sarma@works

  21. Lipid Profile Report PP Fasting Dr.Sarma@works

  22. Lipid Calculations 200 • Total Cholesterol HDL Cholesterol LDL Cholesterol (TC –(HDL+VLDL)) VLDL Cholesterol (1/5 of TG) B. Triglycerides 50 120 30 150 Dr.Sarma@works

  23. The Good and Bad • Total Cholesterol < 200 • ‘Good’ Cholesterols • HDL 1, HDL 2, HDL 3 > 50 • ‘Bad’ Cholesterols (Non HDLc) < 150 • LDLc, IDLc < 100 • VLDLc, VLDLr < 30 • Lp(a), small LDL < 20 HDL 1 and HDL 2 are protective Dr.Sarma@works

  24. How it should be reported ? Interpretation HDL – N,LDL – High , TG - HIGH Dr.Sarma@works

  25. Today’s Safer Values • Total Cholesterol < 200 • Triglycerides < 150 • LDL Cholesterol < 100 • HDL Cholesterol > 50 (for women 55) • Bad Cholesterols the lower the better • Good Cholesterols the higher the better • Non HDL Cholesterol < 130 • Lp(a) values < 20 • Homocysteine < 14 μ mols per liter Dr.Sarma@works

  26. Indian Specialty A. Isolated low LDL 32.90% B. Isolated low HDL 21.35% C. Isolated high TG 10.45% ↑TG ↑LDL The Triad ↓HDL IHJ, 2000, 52: 173-177 Am J Med, 1998, vol 105(1A), 48S-56S Dr.Sarma@works

  27. Look at the risks • Low HDL + High LDL + • LP(a) excess > 30 mg% + • LP(a) excess > 30 mg% + LDL high ++ • LP(a) excess > 30 mg% + low HDL +++ • LP(a) excess > 30 mg% + Incr. tHCy ++++ • LP(a) excess + Incr. tHCy + low HDL +++++ • Circulating lipids are one aspects • Tissue lipid content is more important J. Atherosclerosis : Hopkins PN, 1997 – 17, 2792 Dr.Sarma@works

  28. Relative risk of CHD 1.6 6 Dr.Sarma@works

  29. CM MTP ACAT Intestinal Cholesterol Absorption Biliarycholesterol Dietarycholesterol Intestinal epithelial cell Through lymphatic system to the liver Luminalcholesterol Cholesteryl esters Bile acid excretion (esterification) ABCG5ABCG8 Micellarcholesterol Freecholesterol uptake Bays H et al. Expert Opin Pharmacother 2003;4:779-790. Dr.Sarma@works

  30. Cholesterol Absorption Lymph Enterocyte IntestinalLumen Ezetimibe Cholesterol NPC1L1 ACAT CholesterylEster ABCG5/G8 Avasimibe Dr.Sarma@works

  31. Liver Duodenum BiliaryTransportand Storage Jejunum Ileum Colon Fat Absorption Dr.Sarma@works

  32. Triglyceride Absorption Lymph Enterocyte IntestinalLumen 2 Fatty Acid + Monoglyceride DGAT Triglyceride Dr.Sarma@works

  33. Chylomicron Formation Lymph Enterocyte IntestinalLumen CM apoB48 Triglyceride CholesterylEster Dr.Sarma@works

  34. Structure of HDL Particle A-I A-I CE TG A-II A-I, A-II = apolipoprotein A-I, A-II; CE = cholesterol ester; TG = triglycerides Dr.Sarma@works

  35. A-I CE HDL Types A-I CE CE A-II A-II HDL 1 HDL 2 HDL 3 APO A I Protective Alcohol increases Dr.Sarma@works

  36. MF in Vascular Endothelium LIVER EC Free Chol. HDL Reverse Cholesterol Transport UEC L CAT Enzyme Dr.Sarma@works

  37. A-I CE HDL Metabolism and Reverse Cholesterol Transport Bile A-I FC CE CE LCAT FC FC ABC1 Nascent HDL SR-BI Macrophage Liver Mature HDL ABC1 = ATP-binding cassette protein 1; A-I = apolipoprotein A-I; CE = cholesteryl ester; FC = free cholesterol; LCAT = lecithin:cholesterol acyltransferase; SR-BI = scavenger receptor class BI Dr.Sarma@works

  38. Role of CETP in HDL Metabolism Bile Macrophage Nascent HDL Mature HDL A-I A-I FC CE CE LCAT FC CE ABC1 FC SR-BI SRA CETP X Liver LDLR Oxidation CE B VLDL/LDL CETP = cholesteryl ester transfer proteinLDL = low-density lipoprotein LDLR = low-density lipoprotein receptorVLDL = very-low-density lipoprotein Torcitrapib Dr.Sarma@works

  39. Hyperlipidemias Primary 5% Familial & genetic Secondary 95% Dr.Sarma@works

  40. Secondary Hyperlipidemia Dr.Sarma@works

  41. Clinical Action • Presence of secondary causes of Hyperlipidemia • Order for full lipid profile (LP) – HT also • Presence of hyperlipidemia – increased TG or EC • Investigate for all secondary causes • For all above 20 years once in every 5 years • For those above 45 yrs – once in 2 years • For those with already known lipid abnormality follow-up every 3-6 months • Extended Lipid profile includes Homocysteine, LP(a), SD-LDL, ALP, Apo A and Apo B, HS-CRP Dr.Sarma@works

  42. Clinical Photoes Tuberous xanthoma. Flat-topped, yellow, firm tumor Xanthelasma. Multiple, longitudinal, creamy-orange, slightly elevated papules on eyelids . Dr.Sarma@works

  43. Clinical Photoes Tendinous xanthomas. Large sub-cutaneous tumors adherent to the Achilles tendons. Papular eruptive xanthomas. Multiple, discrete, red-to-yellow confluent papules Dr.Sarma@works

  44. Evaluation • History of eruptive xanthomas, Abd. pain • H/o wt. gain, DM, estrogens, Alcohol, Ex. • Fasting Lipid profile (TC, LDL, HDL, TG) • OGTT, TSH, Liver & Renal Function tests • CHD assessment by ECG, TMT, Angio • Risk factor assessment, Family H/o P.CHD Dr.Sarma@works

  45. Treatment Strategy Lipid Profile, Risk Assessment LDL > 100 Look For Sec. Causes Treat the cause, if found Treatment NO CHD CHD + Primary Prevention Sec. Prevention LDL < 130 2 or more RF < 2 RF Low Risk High Risk LDL > 100 LDL <160 Dr.Sarma@works

  46. Treatment Plan - LDLc For Indians all the values must be 20 mg less Dr.Sarma@works

  47. Treatment Options • Diet – Two step approach • Drug therapy • HMG¢co A Reductase Inhibitors • Fibric Acid derivatives • Nicotinic Acid • Ezetimibe • Bile Acid binding Resins (BAR) • Probucol ¢HMG is Hydroxy Methyl Glutaryl Dr.Sarma@works

  48. New Treatments Drug therapy • Colesevelam (BAR) • Phytosterols • Avasimibe – ACAT inhibitor • Torcetrapib – CETP inhibitor • Drugs decreasing Apo B synthesis Dr.Sarma@works

  49. Therapeutic Lifestyle Changes - TLC Nutrient Recommended Intake • Saturated fat < 7% of calories • PUFA fat Up to 10% of calories • MUFA fat Up to 20% of calories • Total fat 25–35% of calories • Carbohydrate 50–60% of calories • Fiber 20–30 grams per day • Protein Approx. 15% of calories • Cholesterol Less than 200 mg/day DIETARY THERAPY Dr.Sarma@works

  50. Our dietary fats • SFA (saturated) – meet and diary products, coconut oil, Kernel, Ghee, Butter, Palm oil, • Trans fatty acids in vanaspati, chocolates confectionaries, baked, deep fat fried food • MUFA (N1) – Olive oil, Gingili oil • PUFA (N6) – Soya, Sun Flower oil, GN oil • PUFA (N3) – Fish oils – Twice a wk ↓ 76% CAD • Legumes, fruits, olive oil – ↓ all cause mortality Dr.Sarma@works

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