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Dr. R.V.S.N.Sarma, M.D., M.Sc (Canada)

Dr. R.V.S.N.Sarma, M.D., M.Sc (Canada). Consultant Physician and Chest Specialist 1, Jayanagar, Tiruvallur, Chennai -602 001. (04116) – 260593, 263665 Mobile : +91-98940 60593 subha-rani@eth.net. Best Wishes to You All. From IMA Tamil Nadu. LIPIDS. An overview of

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Dr. R.V.S.N.Sarma, M.D., M.Sc (Canada)

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  1. Dr. R.V.S.N.Sarma, M.D., M.Sc (Canada) Consultant Physician and Chest Specialist 1, Jayanagar, Tiruvallur, Chennai -602 001 (04116) – 260593, 263665 Mobile : +91-98940 60593 subha-rani@eth.net Dr.Sarma

  2. Best Wishes to You All Dr.Sarma From IMA Tamil Nadu

  3. LIPIDS An overview of Normal and Abnormal Lipids Dr.Sarma

  4. Lipid Abnormalities Diets rich in Saturated Fat, Chol Sedentary Life Style Excess body weight/ Obesity ROS Less perfect Genetic make-up Lipid abnormalities Atherosclerotic vascular disease CHD, CVD, PVD tHcy Dr.Sarma

  5. AVD – Clinical Manifestations For every thing the common denominator is ED Dr.Sarma

  6. Lipids and Lipoproteins • Lipids or Fats in our body are mainly • The non polar, hydrophobic, inner core of • Triglycerides (TG) • Cholesterol Esters (EC) • The polar, surface monolayer, hydrophilic • Phospholipids (PL) and Free Cholesterol (C) • Apoproteins are the outer coat - amphipathic Dr.Sarma

  7. Lipoprotein Lipids or Fats (Hydrophobic) Size < RBC TG, EC Apoproteins A, B, C, E, (a) (Amphipathic) Phospholipids Free Cholesterol (Hydrophilic) Dr.Sarma

  8. TG EC Apoprotein boat Lipid Transport Solubilizes Apo A = HDL Apo B100+C+E = VLDL, IDL Apo B100 = LDL Apo B48+C+A+E = Chylomicrons Dr.Sarma

  9. Composition TG 95 % TG 80 % EC 20% EC 5% Chylomicrons VLDL Dr.Sarma

  10. Composition TG 15 % TG 5 % EC 95% EC 85% LDL HDL Dr.Sarma

  11. Chylomicrons << 1.006 VLDL < 1.006 IDL < 1.019 LDL Small LDL HDL < 1.063 < 1.085 < 1.210 Particle size & Density Atherogenicity is a function of the density Dr.Sarma

  12. Lipoproteins Dr.Sarma

  13. Lipoprotein Metabolism • Exogenous • Transport of dietary fats – TG to Adipose tissue, Muscle and Cholesterol to Liver as Chylomicrons • Endogenous • Transport of TG and CE from Liver to the peripheral tissues like muscle, adipose tissues and vascular endothelium via VLDL,IDL, LDL • Reverse Cholesterol transport –HDL Path • from the vessels and periphery to liver Dr.Sarma

  14. Vascular Endothelial Cell LIVER EC Free Chol. HDL Reverse Cholesterol Transport UEC L CAT Enzyme Dr.Sarma

  15. Enzymes • Lipo Protein Lipase (LPL) • Synthesized in Adipose and Muscle tissues • Essential for TG metabol – FFA and Glycerol • Insulin activates LPL,- CII apo binds to LPL • Hepatic TG Lipase (HTGL) • Removes TG from VLDL, IDL LDL • Clears the Cholesterol remnants into liver • Converts HDL2 to HDL3in the liver Dr.Sarma

  16. Enzymes contd.. • Lecithin Chol Acyl Transferase (LCAT) • Secreted into plasma by the liver • Binds to HDL and transfers linoleate from lecithin to free Chol and converts it into EC- • Cholesterol Ester Transfer Protein (CETP) • Secreted into plasma from liver • Transfers EC from HDL to VLDL • Converts LDL to small Dense LDL Dr.Sarma

  17. 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

  18. Lipid Peroxidation Dr.Sarma

  19. Dr.Sarma

  20. Primary Hyperlipidaemias Dr.Sarma

  21. Secondary Hyperlipidemia Dr.Sarma

  22. Clinical Photos Tuberous xanthoma. Flat-topped, yellow, firm tumor Xanthelasma. Multiple, longitudinal, creamy-orange, slightly elevated papules on eyelids . Dr.Sarma

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

  24. 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

  25. 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 > RF < 2 RF Low Risk High Risk LDL > 100 LDL >160 Dr.Sarma

  26. Treatment Strategy Fasting TG Level TG < 150 Normal ↑Fasting TG Level < 2 RF Diet Modif. TG >150, No CHD 2 or > RF Diet + Fibrate TG > 150, CHD + Diet + Fibrate + Niasyn TG > 500, CHD +/- Diet + Fibrate + Statin Dr.Sarma

  27. 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 – LP • For those above 45 yrs – once in 2 years • For those with already known lipid abnormality follow-up every 3-6 months Dr.Sarma

  28. Lipid Profile Report Dr.Sarma

  29. Lipid Profile Report Dr.Sarma

  30. LDLc Calculation LDLc = TC – (HDLc + TG/5) e.g. if TC = 250, HDLc = 50, TG = 150 LDLc = 250 – (50 + 150/5) = 250 – (50+30) = 250 – (80) LDLc = 170 Dr.Sarma

  31. Adult Treatment Panel III (ATP III) Guidelines -2002 National Cholesterol Education Program - NCEP Dr.Sarma

  32. Categories of Risk Factors • Major, independent risk factors • Life-habit risk factors • Emerging risk factors • CHD risk equivalents Dr.Sarma

  33. Major Risk Factors for CHD - LDLc • Cigarette smoking • Hypertension (BP 140/90 mmHg or on antihypertensive medication) • Diabetes Mellitus • Low HDL cholesterol (< 40 mg/dl)† • Family history of premature CHD • CHD in first degree ♂ relative of < 55 years • CHD in first degree ♀ relative < 65 years • Age (men  45 years; women  55 years) † HDL cholesterol  60 mg/dL counts as a “negative” risk factor;. Dr.Sarma

  34. Risk Factors Ranking in the PROCAM Study Smoking 2.3 0.001 LDL cholesterol (mg/dl) 130-160 1.9 0.01 >160 4.3 0.001 Hypertension 1.8 0.001 HDL cholesterol (mg/dl) 55 - 45 1.7 0.01 < 45 2.7 0.001 Triglycerides (mg/dl) 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 Dr.Sarma

  35. ↑TG ↑LDL ↓HDL Dyslipidemia in Indiansuncomplicated non diabetic hypertensives(3182) vs controls (4131) A. Hypercholesterolemia 32.90% B. Low HDL 21.35% C. Isolated elevated triglycerides 10.45% D. Abnormal TC/HDL ratio 32.00% E. Abnormal TC/HDL ratio with elevated Tg 15.35% D+E 47.35% The Triad IHJ, 2000, 52: 173-177 Am J Med, 1998, vol 105(1A), 48S-56S Dr.Sarma

  36. Life-Habit Risk Factors • Obesity (BMI  30) • Physical inactivity • Atherogenic diet Dr.Sarma

  37. Emerging Risk Factors • Lipoprotein (a) • Homocysteine • Prothrombotic factors • Pro-inflammatory factors • Impaired fasting glucose 110- 126 • Sub-clinical atherosclerosis Dr.Sarma

  38. CHD Risk Equivalents • Diabetes Mellitus • Reno-vascular Disease • Chronic Nephropathy • Peripheral Vascular Disease • Established CVA All forms of AVD Dr.Sarma

  39. New Features of ATP III • Focus on Multiple Risk Factors • Diabetes: CHD risk equivalent • Framingham projections of 10-year CHD risk • Identify patients with multiple risk factors for more intensive treatment • Multiple metabolic risk factors (metabolic / X syndrome, IR) Dr.Sarma

  40. New Features of ATP III cont.. • Modification of Lipid and Lipoprotein Classification • LDL cholesterol < 100 mg/dl—optimal • HDL cholesterol < 40 mg/dl • Categorical risk factor • Raised from < 35 mg/dl • Lower triglyceride classification cut points • More attention to moderate elevations • > 150 mg itself is indication for Rx. Dr.Sarma

  41. New Features of ATP III cont.. • LDL cholesterol is the primary target for therapy • Non HDL Cholesterol is the secondary target for therapy Non HDLc = (TC – HDLc) = (LDLc + VLDLc) Dr.Sarma

  42. New Features of ATP III (continued) New Recommendation for Screening/Detection • Complete lipoprotein profile preferred • Fasting (12 h) TC, LDL, HDL, TG • Secondary option • Non-fasting total cholesterol and HDL • If TC. is 200 mg/dL or HDL < 40, then proceed to do a full Lipid Profile Dr.Sarma

  43. Approach to Therapy • Education on diet and exercise • Increase physical activity • Decrease body weight • Employ drug therapy Dr.Sarma

  44. Treatment Plan - LDLc Dr.Sarma

  45. Triglycerides NCEP 2002 Guidelines by expert panel on TG Dr.Sarma

  46. Treatment Options • Diet – Two step approach • Drug therapy • HMG¢ CoA Reductase Inhibitors • Bile Acid binding Resins • Nicotinic Acid • Fibric Acid derivatives • Probucol ¢HMG is Hydroxy Methyl Glutaryl Dr.Sarma

  47. 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

  48. ATP III Guidelines Drug Therapy Dr.Sarma

  49. HMG CoA Reductase Inhibitors (Statins) • Chol. synthesis is ↓by enzyme inhibition • Reduce LDL-C 18–55% & TG 7–30% • Raise HDL-C 5–15%, No action on Lp(a) • Major side effects – (< 5%) 1. Myopathy 2. Increased liver enzymes • Contraindications 1. Absolute: liver disease 2. Relative: use with certain drugs Dr.Sarma

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

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