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DYSLIPIDEMIA

DYSLIPIDEMIA. What’s The Big FAT Deal?. CHOLESTEROL. A soft waxy substance found among lipids (fats) in the bloodstream and all cells Needed for digesting fats, making hormones, building cell walls

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DYSLIPIDEMIA

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  1. DYSLIPIDEMIA What’s The BigFATDeal?

  2. 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

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

  4. 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 hx of atherosclerotic dx. • Or serum cholesterol level >240mg/dl. • Physical signs of hyperlipidemia.

  5. 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.

  6. Secondary Dyslipidemia(Medical Conditions Associated with dyslipidemia) • Diabetes • Hypothyroidism • Cholestatic liver disease. • Nephrotic syndrome • cigarette smoking

  7. SECONDARY DYSLIPIDEMIA (Drugs causing mild to moderate degrees of dyslipidemia) • Beta-blockers • Thiazide diuretics • Antiretroviral drugs • Hormonal agents

  8. 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 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. Hormones regulate the release from fat tissue to meet the body’s needs for energy between meals.

  9. 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

  10. 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

  11. 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 1st degree relative <55 years old • CHD in female 1st 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

  12. Risk Assessment for CHD DM 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

  13. Framingham Heart Study 10-year CHD Risk Prediction Score Sheet

  14. Current ATP III Guidelines for Treating LDL Cholesterol

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

  16. Nutrient Recommendations of TLC Diet NutrientRecommended Intake • Saturated fat < 7% of total calories • Polyunsaturated fat Up to 10% of total calories • Monounsaturated fat Up to 20% of total calories • Total fat 25-30% of total calories • Carbohydrates 50-60% of total calories • Fiber 20-30 grams/day • Protein Approx. 15% of total calories • Cholesterol <200 mg/day • Total calories Balance energy intake and expenditure to maintain desirable body weight/ prevent weight gain

  17. 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

  18. 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)

  19. Specific Dyslipidemias: Elevated Triglycerides Classification of Serum Triglycerides Normal <150 mg/dl Borderline High 150-199 mg/dl High 200-499mg/dl Very High >500 mg/dl

  20. 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

  21. 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

  22. Advanced Lipid Analysis:Size DoesMatter

  23. Advanced Lipid Analysis • LDL type “floats” around in the blood • Most LDL around 260 Angstroms • 5% smaller diameter LDL particle leads to a 50% increase in rate of uptake by the arterial wall • LDL particle <258 Angstroms more atherogenic • Large LDL: Pattern A • Small LDL: Pattern B (bad) • Not measured in traditional lipid profiles

  24. Advanced Lipid Analysis: Lp(a) • Fairly large molecule but easily oxidized (more toxic) • Protein “tail” can stimulate blood clotting • Not affected by foods; appears to be genetic • Not affected much by “statins” or fibrates • Niacin, vitamin E combat tendency to be oxidized • Lowering LDL to <80-100 also minimizes toxicity

  25. Advanced Lipid Analysis(Berkeley Heart Labs/ NMR LipoProfile) • Who Needs Advanced lipid analysis? • CHD, DM, or CHD equivalent • Metabolic Syndrome • Multiple Risk Factors • Family Hx premature CHD • Isolated low HDL cholesterol

  26. 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)

  27. 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

  28. Lipid Lowering Drugs Cholesterol Absorption Inhibitor: Zetia • Monotherapy or in combination with statin • Not recommended with fibrates • 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

  29. 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)

  30. 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

  31. Comparison of Lipid Lowering Drugs

  32. Cholesterol Control With Foods and Herbs • Fiber: Decreases LDL; increases HDL • Carrots/Grapefruit: Fiber and pectin (whole fruits most beneficial) • Avocado: monounsaturated fat • Beans: High in fiber, low fat; contain lecithin • Phytosterols: sesame, safflower, spinach, okra, strawberries, squash, tomatoes, celery, ginger. • Shiitake mushrooms: contain lentinan (25% reduction in animal studies) • Garlic, onion oil: lowers chol. 10-33% • Omega 3 fish oils • Red Yeast Rice: a natural substance that inhibits HMG-CoA reductase. Same ingredient in Lovastatin.

  33. What Is On the Horizon? • Glabridin(licorice root/anise plants): Inhibits oxidation of LDL • Study of genetic alterations: cholesterol medications tailored to specific genetic profiles • Microsomal triglyceride transfer protein (MTP): the gene for MTP provides blueprint for production of the protein that helps assemble LDL. Those who carry 2 copies of a variant form of the gene had LDL levels 22% lower than those who had one or no copy of the variant. Some drug companies have already begun looking at MTP inhibitors to help lower LDL • Lecithin-cholesterol acetyltransferase (LCAT): an enzyme bound to HDL acts as a powerful antioxidant (reduce oxidation of chol.) • Thyroid hormones: Molecules similar to thyroid hormones could assist with weight loss and cholesterol reduction. 2 kinds of receptors that receive the hormone and pass its signal to the body.

  34. Cholesterol Meds in the News Vytorin (Zocor + Zetia) • ENHANCE trial • New England Journal of Medicine • 720 FH patients over one year • Endpoint: Carotid artery intima-media thickness (CIMT) per ultrasound • Findings: Vytorin did not reduce CIMT compared to Zocor alone • TAKE HOME: It’s NOT just about the numbers

  35. Cholesterol Meds in the News Crestor • JUPITER trial • Does Crestor reduce major CV events in pts with no existing symptoms, low-normal LDL but higher CRP (c-reactive protein: marker of inflammation)? • Study D/C’d: early findings confirm reduced deaths and CV risks • The ONLYstatin shown to reduce Atherosclerotic plaque

  36. Other Interesting Studies Atherosclerosis: Maternal smoking disturbs lipid profiles in adult offspring • Children ages 5-19 years (N=350) • Total chol. in children whose mothers smoked increased by 4.6mg/dl more each decade than total chol. levels in other children. • Could lead to an increase of 10mg over a 30 year period

  37. Other Interesting Studies The American Journal of Human Genetics : Researchers have identified a novel genetic determinant of dyslipidemia and possibly CVD • Genotyping of 1955 volunteers with HTN • 25 serum and urine biochemical tests • Compared with genome-wide data from 2 other studies of individuals with DM • Found 2 proteins that were associated with a 6% increase in non-fasting serum levels of LDL chol.

  38. Other Interesting Studies American Journal of Medicine: Framingham Offspring Study suggests that at least HALF of U.S. citizens will develop dyslipidemia at some point in their lives • 4701 participants who were ages 30-54 yrs in 1971 • During the following 30 years, 6 in 10 developed borderline-high (> 130) LDL and 4 in 10 developed high (>160) LDL • Study possible suggests that over 70% of Americans may be eligible for statin treatment at some stage of their lives

  39. Other Studies: The GOOD News Nutrition,Metabolism and Cardiovascular Diseases:Drinking moderate amounts of beer appears to improve the lipid profile of healthy adults (esp. women) • 57 healthy Spanish volunteers (29 women) • Abstain for 30 day wash out period, then drink moderate (330ml for women, 660ml for men) amounts of beer for 30 days • HDL increased from 60.7-66.8 mg/dl in women and from 44.2-46.5 mg/dl in men • HDL decreased during the 30 day wash out period

  40. Other Studies: The GOOD News Journal of Nutrition: People with dyslipidemia can improve their lipid profiles by drinking cocoa • 160 volunteers drank 10.0, 19.5 or 26 g/day of cocoa or placebo • After 4 weeks, all groups but placebo had lower LDL levels • Most significant reductions in those with baseline LDL > 125 • LDL decreased from 160 to 152 • HDL increased from 57 to 62 • Decrease in (apo) B and oxidized LDL cholesterol • Polyphenols in cocoa, tea, wine, fruit and vegetables may lead to decrease in atherosclerotic disease

  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)

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