1. Mahesh Moolani, M.D. Diplomat American Board Of Internal Medicine and Lipidology What’s The Big FAT Deal?

3. CHOLESTEROL  A soft waxy substance found among lipids (fats) in the bloodstream and all cells  Needed for digesting fats, making hormones, building cell walls  Carried in particles called lipoproteins that act as transport vehicles delivering cholesterol to various body tissues to be used, stored or excreted  Excess circulating cholesterol can lead to plaque formation- Atherosclerosis

4. HYPERLIPIDEMIA OR DYSLIPIDEMIA (A consequence of abnormal lipoprotein metabolism)  Elevated Total Cholesterol (TC)  Elevated Low-density lipoproteins (LDL)  Elevated triglycerides (TG)  Decreased High-density lipoproteins (HDL)

5. The story of lipids  Chylomicrons transport fats from the intestinal mucosa to the liver  In the liver, the chylomicrons release triglycerides and some cholesterol and become low-density lipoproteins (LDL).  LDL then carries fat and cholesterol to the body’s cells.  High-density lipoproteins (HDL) carry fat and cholesterol back to the liver for excretion.

6. The story of lipids (cont.)  When oxidized LDL cholesterol gets high, atheroma formation in the walls of arteries occurs, which causes atherosclerosis.  HDL cholesterol is able to go and remove cholesterol from the atheroma.  Atherogenic cholesterol → LDL, VLDL, IDL

7. Types of Cholesterol LDL- (“bad” cholesterol) The major cholesterol carrier in the blood. Excess most likely to lead to plaque formation. Goal: LOW HDL- (“good” cholesterol) Transports cholesterol away from arteries and back to the liver to be eliminated. Removes excess cholesterol from plaques, slowing growth. Goal: HIGH

8. TYPES ( CONT.)  Triglycerides- the chemical form in which most fat exists in foods as well as in the body. Present in blood plasma and together with cholesterol, form the plasma lipids. Made in the body from other energy sources like carbohydrates. Calories ingested in a meal and not immediately used by tissues are converted to triglycerides..

9. PRIMARY DYSLIPIDEMIA ETIOLOGY  SINGLE OR MULTIPLE GENE MUTATION –RESULTING IN DISTURBANCE OF LDL, HDL AND TRIGYLCERIDE, PRODUCTION OR CLEARANCE.  Should be suspected in patients with  premature heart disease  family hxof atherosclerotic dx.  Or serum cholesterol level >240mg/dl.  Physical signs of hyperlipidemia.

10. Hereditary Causes of Hyperlipidemia  Familial Hypercholesterolemia  Occurs in 1 in 500 individuals  Mutation in LDL receptor, resulting in elevated levels of LDL at birth and throughout life  High risk for atherosclerosis, tendon xanthomas (75% of patients), tuberous xanthomas and xanthelasmas of eyes.  Familial Combined Hyperlipidemia  Increased secretions of VLDLs  Dysbetalipoproteinemia  Affects 1 in 10,000  Increased risk for atherosclerosis, peripheral vascular disease  Tuberous xanthomas, striae palmaris

11. Causes of SECONDARY Hyperlipidemia  Diet  Hypothyroidism  Nephrotic syndrome  Anorexia nervosa  Obstructive liver disease  Obesity  Diabetes mellitus  Pregnancy  Obstructive liver disease  Acute heaptitis  Systemic lupus erythematousus  AIDS (protease inhibitors)

12. SECONDARY DYSLIPIDEMIA (Most adult cases of dyslipidemia are secondary in nature in western civilizations)  Sedentary lifestyle  Excessive consumption of cholesterol – saturated fats and trans-fatty acids.

13. Specific Dyslipidemias: Very High LDL (> 190mg/dl) Causes and Diagnosis  Genetic disorders Monogenic familial hypercholesterolemia Familial defective apolipoprotein B-100 (Apo B) Polygenic hypercholesterolemia  Family testing to detect affected relatives

17. Dietary sources of Cholesterol Type of FatMain SourceEffect on Cholesterol levels MonounsaturatedOlives, olive oil, canola oil, peanut oil, cashews, almonds, peanuts and most other nuts; avocados Lowers LDL, Raises HDL PolyunsaturatedCorn, soybean, safflower and cottonseed oil; fish Lowers LDL, Raises HDL SaturatedWhole milk, butter, cheese, and ice cream; red meat; chocolate; coconuts, coconut milk, coconut oil, egg yolks, chicken skin Raises both LDL and HDL TransMost margarines; vegetable shortening; partially hydrogenated vegetable oil; deep- fried chips; many fast foods; most commercial baked goods Raises LDL

18. Why Do We Care? According to the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Cholesterol in Adults (NCEP ATP-III): High LDL levels are a leading cause of coronary heart disease (CHD) and should be the main target of any cholesterol lowering regimen

19. Checking lipids  Nonfasting lipid panel  measures HDL and total cholesterol  Fasting lipid panel  Measures HDL, total cholesterol and triglycerides  LDL cholesterol is calculated:  LDL cholesterol = total cholesterol – (HDL + triglycerides/5)

20. When to check lipid panel  Two different Recommendations  Adult Treatment Panel (ATP III) of the National Cholesterol Education Program (NCEP)  Beginning at age 20: obtain a fasting (9 to 12 hour) serum lipid profile consisting of total cholesterol, LDL, HDL and triglycerides  Repeat testing every 5 years for acceptable values

21. ATP III Lipid and Lipoprotein Classification LDL Cholesterol (mg/dl) HDL Cholesterol (mg/dl) <100 Optimal < 40 Low 100-129 Near/Above Optimal > 60 High (Desirable) 130-159 Borderline High 160-189 High >190 Very High Categories of Risk that Modify LDL Goals CHD and CHD risk equivalents<100 Multiple (2+) risk factors<130 Zero to one risk factor<160

22. Major Risk Factors For CHD That Modify LDL Goals Cigarette smoking Hypertension (BP >140/90 or on BP med) Low HDL cholesterol (<40mg/dl) Family Hx premature CHD - CHD in male 1 st degree relative <55 years old - CHD in female 1 st degree relative <65 years old Age (men >45 yrs. women >55 yrs)  HDL >60 counts as a “negative” risk factor. It’s presence removes one risk factor from the total count

23. Risk Assessment for CHD Diabetes regarded as a CHD equivalent For patients with multiple (2+) risk factors -Perform 10 year risk assessment For patients with 0-1 risk factor -Most have 10 year risk assessment <10%; risk assessment scoring unnecessary

24. Current ATP III Guidelines for Treating LDL Cholesterol Risk Category LDL Goal (mg/dl) LDL level to initiate TLC LDL level to consider Rx therapy CHD or Equivalents <100 <70 Ideal > 100 > 130 (100-129 Rx optional) 2+ Risk Factors <130 > 130 > 130 (10 Year risk 10-20%) > 160 (Risk 160 (Risk <10%) 0-1 Risk Factor <160 > 160 > 190 (160-189 Rx optional)

25. A Model of Steps in Therapeutic Lifestyle Changes (TLC) Visit 1 Begin TLC Emphasize reduction in saturated fat & chol. Encourage moderate Physical activity Consider referral to dietician Visit 2 (6 wks) Eval. LDL response Intensify Tx if not to goal Reinforce dietary recommendations Consider adding plant stanols/sterols Increase fiber intake Consider dietician Visit 3 (6 wks) Eval LDL response Consider adding Rx if not to goal Evaluate for Metabolic syndrome Intensify wt mgmt & physical activity Consider dietician Visit N Monitor adherence to TLC Q4-6 mos

26. Nutrient Recommendations of TLC Diet Nutrient Recommended Intake  Saturated fat< 7% of total calories  Polyunsaturated fatUp to 10% of total calories  Monounsaturated fatUp to 20% of total calories  Total fat25-30% of total calories  Carbohydrates50-60% of total calories  Fiber20-30 grams/day  ProteinApprox. 15% of total calories  Cholesterol<200 mg/day  Total caloriesBalance energy intake and expenditure to maintain desirable body weight/ prevent weight gain

28. Food Pyramid

30. Medications for Hyperlipidemia Drug ClassAgentsEffects (% change)Side Effects HMG CoA reductase inhibitors Lovastatin Pravastatin  LDL (18-55),  HDL (5-15)  Triglycerides (7-30) Myopathy, increased liver enzymes Cholesterol absorption inhibitor Ezetimibe  LDL( 14-18),  HDL (1-3)  Triglyceride (2) Headache, GI distress Nicotinic Acid  LDL (15-30),  HDL (15-35)  Triglyceride (20-50) Flushing, Hyperglycemia, Hyperuricemia, GI distress, hepatotoxicity Fibric AcidsGemfibrozil Fenofibrate  LDL (5-20),  HDL (10-20)  Triglyceride (20-50) Dyspepsia, gallstones, myopathy Bile Acid sequestrants Cholestyramine  LDL  HDL No change in triglycerides GI distress, constipation, decreased absorption of other drugs

31. Specific Dyslipidemias: Low HDL Causes of Low HDL (<40 mg/dl)  Elevated triglycerides  Overweight and obesity  Physical Inactivity  Type 2 diabetes  Cigarette smoking  Very high carb. intakes (>60% energy)  Medications (some beta blockers, anabolic steroids, progestational agents)

32. Specific Dyslipidemias: Elevated Triglycerides Classification of Serum Triglycerides Normal<150 mg/dl Borderline High150-199 mg/dl High200-499mg/dl Very High>500 mg/dl

33. Specific Dyslipidemias: Elevated Triglycerides Causes of Elevated Triglycerides  Obesity and overweight  Physical Inactivity  Cigarette smoking  Excess alcohol intake  High carb. diets  Several diseases (Type 2 DM, chronic renal failure, nephrotic syndrome  Medications (corticosteroids, estrogens, retinoids, higher doses of beta blockers

34. Specific Dyslipidemias: Elevated Triglycerides Management of Very High Triglycerides (>500 mg/dl)  Goal of therapy: Prevent acute pancreatitis  Very low fat diets (< 15% of caloric intake)  Triglyceride-lowering drug usually required (fibrate or nicotinic acid)  Reduce triglycerides before lowering LDL

35. Lipid Lowering Drugs HMG-CoA Reductase Inhibitors (Statins)  Partially block an enzyme necessary for formation of cholesterol  Speed removal of LDL from blood  18%-60% reduction in LDL  Most effective at lowering LDL; esp. HS dosing  Liver enzymes MUST be monitored. Check baseline, 3mos., then semi-annually (D/C if > 3x normal limits)  Side effects: Myalgias (D/C if total CK >10x normal), rhabdomyolysis  Metabolized by CP450 (watch for drug interactions)

36. Lipid Lowering Drugs Bile Acid Sequestrants  Convert cholesterol to bile acids  Bind bile acids and prevent reabsorption in the gut  May increase triglyceride levels  Most common side effects: GI-constipation  Alternative for statins

37. Lipid Lowering Drugs Cholesterol Absorption Inhibitor: Zetia  Monotherapy or in combination with statin  Reduces LDL number : esp. Lp(a) Lipid-Regulating Agent: Omega 3 acid ethyl esters (Lovaza)  Omega 3 Fish oil (salmon, herring, mackerel, swordfish, albacore tuna, sardines, lake trout)  Only FDA approved supplement for tx of dyslipidemias  Decreases hepatic production of TG and VLDL  Increases LDL size to large buoyant particles

38. Lipid Lowering Drugs Nicotinic Acid/Niacin  Reduces production and release of LDL  Effective in reduction of triglycerides (<400mg/dl)  Increases HDL  Very effective in increasing LDL particle size  Monitor liver enzymes and glucose  Most common side effect: FLUSHING (take ASA/ibuprofen 30 min. prior and take with light snack). Decreased with time released formulas (Niaspan)

39. Lipid Lowering Drugs Fibric Acid Derivatives/Fibrates  Very effective in reducing triglycerides (>400)  Increase HDL  Containdications: Gallbladder disease, hepatic disease, renal dysfunction  Increase LDL particle size but not quantity  Caution with statins

41. Case Study 1 35 YO male, a police officer. 5’11’’, weight=258 (BMI=35, obese) Hx: hypertension, anxiety. Has taken testosterone supplements in past, now uses “body building” shakes. Family Hx: Father, paternal grandfather-DM Labs: FBS=79, TSH normal

42. Case Study 1 Visit 1 Visit 2 Visit 3 TC= 167 164 158 TG=539 288 260 HDL= 18 24 28 LDL= ? 95 88 Tricor started Niaspan Levaza (intolerant)

43. Case Study 2 39 YO male (hasn’t been in for 2 years) c/o frequent urination, excessive thirst, blurred vision. Hx: Mod. Obesity, BMI= 33 Family Hx: Mother DM Meds: None Non-fasting Accucheck= 297 (3 hrs PP)

44. Case Study 2 TC705252212195144 Trig6710149146128123 HDL17033363942 LDL?19014013182 A1C11.95.65.6 Meds Tricor and DM tx Zocor 20mg Zocor 40mg Add Zetia

45. Case Study 3 62 YO Female with CHD s/p CABG wanted me to manage lipids. Also has Hypertension. Meds: Plavix, Atenolol, lisinopril, Atorvastatin (stopped by pt.-myalgias) Current labs: TC= 248 Trig= 144 HDL= 41 LDL= 156

46. Case Study 3  Changed atenolol to Coreg  Started Pravachol 20mg  Disease management/diet counseling  Resume walking 3-4 days/week  Repeat labs: TC=190 Increase Pravachol …178 Trig= 130to 40mg …128 HDL= 39 …41 LDL= 112 …98

47. Framingham Risk Prediction Score  47 YO Female  Labs: TC= 178 Trig= 133 LDL= 110 HDL= 35  BP: 162/98  Hx: Smoker, non-diabetic What is 10 Year CHD Risk?

48. Framingham Risk Prediction Score  47 YO Female  Labs: TC= 178 Trig= 133 LDL= 110 HDL= 35  BP: 162/98  Hx: Smoker, non-diabetic What is 10 Year CHD Risk? 10% Compared to average of 5% for her age group

49. Treatment of Dyslipidemias (Medication Comparison Chart) Which Medication(s) slows coronary athersclerosis, lowers LDL, increases HDL but has no effect on triglycerides?

50. Treatment of Dyslipidemias (Medication Comparison Chart) Which Medication(s) slows coronary athersclerosis, lowers LDL, increases HDL but has no effect on triglycerides? Mevacor

51. NCEP ATP III Lipid Goals What is the recommended LDL goal for a healthy normo-tensive, non-smoking 46 year old male whose father died of a massive MI at the age of 52?

52. NCEP ATP III Lipid Goals What is the recommended LDL goal for a healthy normo-tensive, non-smoking 46 year old male whose father died of a massive MI at the age of 52? <130 for 2 risk factors (age >45 and father with premature CAD)

53. Final Question!!!!! 58 Year old Male (smoker) Fam. Hx: Mother with NIDDM, sister died age 70 from MI BP= 156/86 Pulse 78 Labs: TC= 310, TG= 250, HDL=29, LDL=156, FBS=88  What is Framingham 10 year Risk score?  Based on score, what is LDL goal?  Name 2 cholesterol medications (Brand) that would be most appropriate for his treatment.

54. Final Question!!!!! 58 Year old Male (smoker) Fam. Hx: Mother with NIDDM, sister died age 70 from MI BP= 156/86 Pulse 78 Labs: TC= 310, TG= 250, HDL=29, LDL=156, FBS=88  What is Framingham 10 year Risk score? 27%  Based on score, what is LDL goal? <100  Name 2 cholesterol medications (Brand) that would be most appropriate for his treatment. Niaspan, any “statin” except Mevacor, any of the combination meds

55. Thank You  Questions?  Glenda Summerville