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O ALMIGHTY

O ALMIGHTY. Tallee ninnu dalanchi pustakamu chaetan boonitin neevu naa ullambanduna nilchi jrumbhanamugaan uktul su sabdambul sobhillan balkumu naadu vaakkunan sampreetin, Jaganmohinee

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O ALMIGHTY

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  1. www.drsarma.in

  2. O ALMIGHTY Tallee ninnu dalanchi pustakamu chaetan boonitin neevu naa ullambanduna nilchi jrumbhanamugaan uktul su sabdambul sobhillan balkumu naadu vaakkunan sampreetin, Jaganmohinee pullaabjaakshee Saraswatee Bhagavatee poornaendu bimbaanana www.drsarma.in

  3. O! ALMIGHTY O! Almighty, the Goddess of Wisdom! We start this learning process, keeping YOU in our inner hearts, please shower Your kind blessings on all of us and ensure What ever we speak is eloquent What ever we discuss is pertinent What ever we learn is relevant. May we be blessed with the best wisdom ! www.drsarma.in

  4. Dyslipidemias- Practice Approach Dr.Sarma RVSN, M.D., M.Sc (Canada) Consultant in Medicine and Chest, # 3, Jayanagar, Tiruvallur – 602 001 98940 60593, 2766 0593 Visit us at : www.drsarma.in www.drsarma.in

  5. CD ROM Available The contents of my today’s presentations are made available in a CD-ROM format This CD, in addition, contains my talks on Asthma, COPD, Hypertension, ECG, CAD Dyslipidemias, Diabetes, Osteoporosis… www.drsarma.in

  6. Pardons and Grants me heaven Even if I don't know a single letter about Crutz Feld Jacob’s Disease Tsutsugamushi Fever Criggler Nazzar Syndrome South American equine encephalitis and Many and much more rarer topics BUT ……. The Almighty Dr.Sarma@works

  7. Will drag me to hell and will not pardon My ignorance of even the minute details of HT, DM My indifference to apply the current knowledge My negligence in screening for Lipids, DM, HT, LVH My despondency about preventing TOD and ACS My inadequacy in maintaining my patients Normotensive, Euglycemic, Eulipidemic – (This is applicable to all common diseases) The Almighty Dr.Sarma@works

  8. Adult Treatment Panel III (ATP III) Guidelines -2002Updated October 2004 National Cholesterol Education Program - NCEP www.drsarma.in

  9. The Good, Bad, Ugly and Deadly www.drsarma.in

  10. Two Types of Lipids www.drsarma.in

  11. Lipoprotein Lipids or Fats (Hydrophobic) Size < RBC TG, EC Apoproteins A, B, C, E, (a) (Amphiphatic) Phospholipids Free Cholesterol (Hydrophilic) www.drsarma.in

  12. TG EC Apoprotein boat www.drsarma.in Lipoproteins Apo A I and A II for HDLApo B100 for LDL Apo B100+C+E for VLDL, IDLApo B100+Apo(a) for Lp(a)

  13. HDL A I, A II B 100+ (a) B 100 TG C C TG TG TG C C B 100 + E +C www.drsarma.in Good, Bad, Ugly & Deadly LDL GOOD BAD VLDL Lp(a) UGLY DEADLY TG

  14. Apolipoprotein B Measurements Non-HDL-C VLDL VLDLR IDL LDL SDL TG-rich lipoproteins www.drsarma.in All are the terrorists !! Highly atherogenic

  15. 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 www.drsarma.in

  16. Lipid Profile Report PP Fasting www.drsarma.in

  17. Normal Lipid Profile • Total Cholesterol < 200 • TG ‘Ugly’ Lipid < 150 • ‘Bad’ Cholesterols LDL < 100 • HDL ‘Good’ cholesterol > 50 • VLDL is Ugly TG ÷ 5 < 30 • Lp(a) ‘Deadly’ cholesterol < 20 www.drsarma.in

  18. How to interpret Lipid Profile Report? 200 • Total Cholesterol HDL Cholesterol (Soldiers) - Good Non HDL Cholesterol(Culprits) LDL Cholesterol – Bad fellows Lipoprotein(a) – Deadly fellows VLDL Cholesterol (1/5 of TG)- Ugly B. Triglycerides 50 150 100 20 30 150 Normal Lipid Profile www.drsarma.in

  19. Interpret this Lipid Profile Report 240 • Total Cholesterol HDL Cholesterol (Soldiers) - Good Non HDL Cholesterol(Culprits) LDL Cholesterol – Bad fellows Lipoprotein(a) – Deadly fellows VLDL Cholesterol (1/5 of TG)- Ugly B. Triglycerides 50 190 140 20 30 150 Hyper cholesterolimia ↑LDL, HDL, TG, Lp(a) - N www.drsarma.in

  20. Interpret this Lipid Profile Report 200 • Total Cholesterol HDL Cholesterol (Soldiers) - Good Non HDL Cholesterol(Culprits) LDL Cholesterol – Bad fellows Lipoprotein(a) – Deadly fellows VLDL Cholesterol (1/5 of TG)- Ugly B. Triglycerides 50 150 70 20 60 300 Hyper triglyceridemia ↑TG, HDL, LDL, Lp(a) - N www.drsarma.in

  21. Interpret this Lipid Profile Report 160 • Total Cholesterol HDL Cholesterol (Soldiers) - Good Non HDL Cholesterol(Culprits) LDL Cholesterol – Bad fellows Lipoprotein(a) – Deadly fellows VLDL Cholesterol (1/5 of TG)- Ugly B. Triglycerides 25 135 85 20 30 150 Low HDL : ↓HDL, LDL, TG, Lp(a) - N www.drsarma.in

  22. Interpret this Lipid Profile Report 200 • Total Cholesterol HDL Cholesterol (Soldiers) - Good Non HDL Cholesterol(Culprits) LDL Cholesterol – Bad fellows Lipoprotein(a) – Deadly fellows VLDL Cholesterol (1/5 of TG)- Ugly B. Triglycerides 45 155 75 50 30 150 High Lipoprotein(a) : ↑Lp(a), HDL, LDL, TG - N www.drsarma.in

  23. Interpret this Lipid Profile Report 200 • Total Cholesterol HDL Cholesterol (Soldiers) - Good Non HDL Cholesterol(Culprits) LDL Cholesterol – Bad fellows Lipoprotein(a) – Deadly fellows VLDL Cholesterol (1/5 of TG)- Ugly B. Triglycerides 25 175 95 20 60 300 High Lipoprotein(a) : ↓HDL, ↑TG, LDL, Lp(a) - N www.drsarma.in

  24. Interpret this Lipid Profile Report 260 • Total Cholesterol HDL Cholesterol (Soldiers) - Good Non HDL Cholesterol(Culprits) LDL Cholesterol – Bad fellows Lipoprotein(a) – Deadly fellows VLDL Cholesterol (1/5 of TG)- Ugly B. Triglycerides 50 210 120 40 50 250 Combined Dyslipidemia : ↑ TC↑LDL↑TG ↑Lp(a) www.drsarma.in

  25. Dyslipidemic Triad A. Isolated High 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 www.drsarma.in

  26. ↑TG ↑Lp(a) The Indian Triad ↓HDL Indian Dyslipidemic Triad IHJ, 2000, 52: 173-177 Am J Med, 1998, vol 105(1A), 48S-56S www.drsarma.in

  27. Indian Dyslipidemia • Low HDL 39.2% • High TG 32.5% • Lp(a) excess 28.6% • High LDL 10.8% • Normal Lipids 23.5% Am J C 2001;88(suppl) 9N-13N; 22N www.drsarma.in

  28. 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 www.drsarma.in

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

  32. A-I A-I CE CE CE A-II A-II HDL 1 HDL 2 HDL 3 APO A I Atheroprotective Alcohol increases Athero-neutral www.drsarma.in HDL Sub types The soldier-like The soldiers

  33. MF in Vascular Endothelium LIVER EC Free Chol. HDL Reverse Cholesterol Transport UEC L CAT Enzyme www.drsarma.in

  34. 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 www.drsarma.in

  35. 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 www.drsarma.in

  36. Hyperlipidemias Primary 5% Familial & genetic Secondary 95% www.drsarma.in

  37. Secondary Hyperlipidemia www.drsarma.in

  38. 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 www.drsarma.in

  39. Clinical Photoes Tuberous xanthoma. Flat-topped, yellow, firm tumor Xanthelasma. Multiple, longitudinal, creamy-orange, slightly elevated papules on eyelids . www.drsarma.in

  40. Clinical Photoes Tendinous xanthomas. Large sub-cutaneous tumors adherent to the Achilles tendons. Papular eruptive xanthomas. Multiple, discrete, red-to-yellow confluent papules www.drsarma.in

  41. 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 www.drsarma.in

  42. The Weapons in our hand • Dietand Exercise (Life Style) • Drug therapy • HMG¢Co A Reductase Inhibitors • Fibric Acid derivatives • Nicotinic Acid • Ezetimibe • Bile Acid binding Resins (BAR) • Probucol ¢HMG is Hydroxy Methyl Glutaryl www.drsarma.in

  43. New Treatments Drug therapy • Colesevelam (BAR) • Phytosterols • Avasimibe – ACAT inhibitor • Torcetrapib – CETP inhibitor • Drugs decreasing Apo B synthesis • Selective LDL apopheresis www.drsarma.in

  44. 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 www.drsarma.in

  45. 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 www.drsarma.in

  46. Treatment of ↑LDLc High LDLc Therapeutic Lifestyle Change Drug Therapy Therapy of Choice: Statin Add on drug - EZ , Niacin, BAR Dr.Sarma@works

  47. VLDL Cholesterol synthesis Apo B LDL receptor (B–E receptor) synthesis VLDLR LDL receptor–mediated hepatic uptake of LDL and VLDL remnants Apo E Serum LDL-C Intracellular Cholesterol Apo B LDL Serum VLDL remnants Serum IDL Hepatocyte Systemic Circulation Statins – Mechanism of Action HMGCoA • Reduce hepatic cholesterol synthesis (HMG CoA), • lowering intracellular cholesterol, • Upregulation of LDL receptor and • ↑ the uptake of non-HDL from circulation. Dr.Sarma@works

  48. Time course of Statin effects Vulnerableplaquesstabilized LDL-C lowered* Inflammationreduced Endothelialfunctionrestored Ischemicepisodesreduced Cardiac eventsreduced* Days Years * Time course established Dr.Sarma@works

  49. HMG CoA Reductase Inhibitors (Statins) Statin Dose Range Lovastatin 20–80 mg Pravastatin 20–40 mg Fluvastatin 20–80 mg Simvastatin 20–80 mg Atorvastatin 10–80 mg Rosuvastatin 5–20 mg Cerivastatin 0.4–0.8 mg Dr.Sarma@works

  50. 10 mg 20 mg 40 mg 80 mg LDL-C Lowering - Statin Dose Atorvastatin211 mg/dl* Simvastatin219 mg/dl* Daily Dose Mean % Change from Baseline 28% 38% 35% 13% 41% 46% 16% with3 Titrations 51% 54% Adapted from Jones P et al. Am J Cardiol 1998;81:582-587. Dr.Sarma@works

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