Hyperlipidemia
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  • In 1997, the International Obesity Task Force,10 convened by the World Health Organization (WHO), recommended a standard classification of adult overweight and obesity
  • Presently, there is no precise clinical definition of obesity based on the degree of excess body fat that places an individual at increased health risk. General consensus exists for an indirect measure of body fatness, called the weight-for-height index or body mass index (BMI). The BMI is an easily obtained and reliable measurement for overweight and obesity and is defined as a person's weight (in kilograms) divided by the square of the person's height (in meters) Other Measurements Waist Circumference >35 inches in women or 40 inches in men indicates hazardous fat distribution Waist/Hip Ratios >0.8 indicates hazardous fat distribution
  • Leptin signals the brain about the quantity of stored fat. Modulates food intake.
  • Waist circumference measurements greater than 40 inches (102 cm) in men and 35 inches (89 cm) in women also indicate an increased risk of obesity-related comorbidities.
  • Waist-hip measurement not likely to be done by busy clinicians. 40 in. = 101.6 cm 35 cm = 88.9 cm

Transcript

  • 1. Hyperlipidemia
  • 2. 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.
  • 3. 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
  • 4. Atherosclerosis
  • 5. Causes of Hyperlipidemia Diet  Obstructive liver Hypothyroidism disease Nephrotic syndrome  Acute heaptitis Anorexia nervosa  Systemic lupus erythematousus Obstructive liver disease  AIDS (protease inhibitors) Obesity Diabetes mellitus Pregnancy
  • 6. Dietary sources of CholesterolType of Fat Main Source Effect on Cholesterol levelsMonounsaturated Olives, olive oil, canola oil, peanut oil, Lowers LDL, Raises cashews, almonds, peanuts and most HDL other nuts; avocadosPolyunsaturated Corn, soybean, safflower and cottonseed Lowers LDL, Raises oil; fish HDLSaturated Whole milk, butter, cheese, and ice cream; Raises both LDL and red meat; chocolate; coconuts, coconut HDL milk, coconut oil , egg yolks, chicken skinTrans Most margarines; vegetable shortening; Raises LDL partially hydrogenated vegetable oil; deep- fried chips; many fast foods; most commercial baked goods
  • 7. Hereditary Causes of Hyperlipidemia Familial Hypercholesterolemia  Codominant genetic disorder, coccurs in heterozygous form  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  Autosomal dominant  Increased secretions of VLDLs Dysbetalipoproteinemia  Affects 1 in 10,000  Results in apo E2, a binding-defective form of apoE (which usually plays important role in catabolism of chylomicron and VLDL)  Increased risk for atherosclerosis, peripheral vascular disease  Tuberous xanthomas, striae palmaris
  • 8. 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)
  • 9. 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  United States Preventative Services Task Force  Women aged 45 years and older, and men ages 35 years and older undergo screening with a total and HDL cholesterol every 5 years.  If total cholesterol > 200 or HDL <40, then a fasting panel should be obtained  Cholesterol screening should begin at 20 years in patients with a history of multiple cardiovascular risk factors, diabetes, or family history of either elevated cholesteral levels or premature cardiovascular disease.
  • 10. Goals for Lipids LDL  HDL  < 100 →Optimal  < 40 → Low  100-129 → Near optimal  ≥ 60 → High  130-159 → Borderline  Serum Triglycerides  160-189→ High  < 150 → normal  ≥ 190 → Very High  150-199 → Borderline Total Cholesterol  200-499 → High  < 200 → Desirable  ≥ 500 → Very High  200-239 → Borderline  ≥240 → High
  • 11. Determining Cholesterol Goal(LDL!) Look at JNC 7 Risk Factors  Cigarette smoking  Hypertension (BP ≥140/90 or on anti- hypertensives)  Low HDL cholesterol (< 40 mg/dL)  Family History of premature coronary heart disease (CHD) (CHD in first-degree male relative <55 or CHD in first-degree female relative < 65)  Age (men ≥ 45, women ≥ 55)
  • 12. Determining Goal LDL CHD and CHD Risk Equivalents:  Peripheral Vascular Disease  Cerebral Vascular Accident  Diabetes Mellitus
  • 13. LDL Goals 0-1 Risk Factors:  LDL goal is 160  If LDL ≥ 160: Initiate TLC (therapeutic lifestyle changes)  If LDL ≥ 190: Initiate pharmaceutical treatment 2 + Risk Factors  LDL goal is 130  If LDL ≥ 130: Initiate TLC  If LDL ≥ 160: Initiate pharmaceutical treatment CHD or CHD Risk Equivalent  LDL goal is 100 (or 70)  If LDL ≥ 100: Initiate TLC and pharmaceutical treatment
  • 14. Treatment of Hyperlipidemia Lifestyle modification  Low-cholesterol diet  Exercise
  • 15. Medications for Hyperlipidemia Drug Class Agents Effects (% change) Side EffectsHMG CoA reductase Lovastatin ↓LDL (18-55),↑ HDL (5-15) Myopathy, increased liverinhibitors Pravastatin enzymes ↓ Triglycerides (7-30)Cholesterol Ezetimibe ↓ LDL( 14-18), ↑ HDL (1-3) Headache, GI distressabsorption inhibitor ↓Triglyceride (2)Nicotinic Acid ↓LDL (15-30), ↑ HDL (15-35) Flushing, Hyperglycemia, ↓ Triglyceride (20-50) Hyperuricemia, GI distress, hepatotoxicityFibric Acids Gemfibrozil ↓LDL (5-20), ↑HDL (10-20) Dyspepsia, gallstones, Fenofibrate myopathy ↓Triglyceride (20-50)Bile Acid Cholestyramine ↓ LDL GI distress, constipation,sequestrants decreased absorption of ↑ HDL other drugs No change in triglycerides
  • 16. OBESITY 17
  • 17. DefinitionA BMI of 25.0 to 29.9 kg per m2 is defined as overweight; a BMI of 30.0 kg per m2 or more is defined as obesity. 18
  • 18. Classification of Overweightand Obesity BMI Classification <18.5 Underweight  18.5-24.9 Normal weight  25-29.9 Overweight  30-34.9 Obesity Class I  35-39.9 Obesity Class II  40-49.9 Obesity Class III  50 and above Super Obesity 19
  • 19. Why is it so hard to lose weight? Brain External factors Emotions Food characteristics Central Signals Lifestyle behaviors Stimulate Inibit Environmental cues NPY Orexin-A α-MSH CART AGRP dynorphin CRH/UCN NE galanin GLP-I 5-HTPeripheral signals Peripheral organs Glucose Gastrointestinal CCK, GLP-1, tract− Apo-A-IV Vagal afferents Food Insulin Intake+ Ghrelin Adipose− Leptin tissue+ Cortisol Adrenal glands
  • 20. Medical Complications of ObesityPulmonary diseaseabnormal functionobstructive sleep apnea Strokehypoventilation syndrome Cataracts CHDNonalcoholic fatty liver disease Diabetessteatosis Dyslipidemiasteatohepatitis Hypertensioncirrhosis Severe pancreatitis Gall bladder disease Cancer Gynecologic abnormalities breast, uterus, cervix abnormal menses colon, esophagus, pancreas kidney, prostate infertility Osteoarthritis PCOS Phlebitis venous stasis Gout 21
  • 21. Weight Loss Strategies Diet therapy Increased Physical Activity Pharmacotherapy Behavioral Therapy Surgery Any combination of the above 22
  • 22. Principles Of Dieting Women should consume atleast 1200 kcal/day, men 1500 kcal/day. Select a diet that has: >75g/day proteins (15% of total calories) > 55% total calories from carbs▪ Fat should contribute 30% or less of total caloriesAtleast 3 meals/day.High fiber (20-30g/day), fruits and vegetables.Supplement the diet with multivitamis and minerals.Avoid sugar containing beverages and fat spreads. 23
  • 23. Surgery Roux-en-Y gastric bypass. Lap band procedureCriteria: a) BMI > 40 or >35 with 2 comorbidities. b) Failure of non surgical methods c) Presence of 2 or more medical conditions that would benefit with weight loss. 24
  • 24. Metabolic SyndromeSymposium
  • 25. Other Names Used: Syndrome X Cardiometabolic Syndrome Cardiovascular Dysmetabolic Syndrome Insulin-Resistance Syndrome Metabolic Syndrome
  • 26. Clustering of Components: Hypertension Hypertriglyceridemia Low HDL-cholesterol Obesity (central) Impaired Glucose Handling Microalbuninuria (WHO)
  • 27. Hypertension: IDF:  BP >130/85 or on Rx for previously Dxed hypertension WHO:  BP >140/90 NCEP ATP III:  BP >130/80
  • 28. Obesity: IDF:  Central obesity - waist circumference >94 cm for Europid men, >80 Europid women with ethnicity specific values for other groups WHO:  Waist-hip ratio >0.9 - men or >0.85 - women ATP III:  Waist circumference >40 in. - men, 35 in. - women
  • 29. Glucose Abnormalities: IDF:  FPG >100 mg/dL (5.6 mmol.L) or previously diagnosed type 2 diabetes WHO:  Presence of diabetes, IGT, IFG, insulin resistance ATP III:  FBS >110 mg%, <126 mg% (ADA: FBS >100)
  • 30. Dyslipidemia: IDF:  Triglycerides - >150mg/dL (1.7 mmol/L)  HDL - <40 mg/dL (men), <50 mg/dL (women) WHO:  Triglycerides - >150 mg/dL (1.7 mmol/L)  HDL - <35 mg/dL (men), >39 mg/dL) women ATP III:  Same as IDF
  • 31. Necessary Criteria to MakeDiagnosis: IDF:  Require central obesity plus two of the other abnormalities WHO:  Also requires microalbuminuria - Albumen/ creatinine ratio >30 mg/gm creatinine ATP III:  Require three or more of the five criteria
  • 32. Resulting Clinical Conditions: Type 2 diabetes Essential hypertension Polycystic ovary syndrome (PCOS) Nonalcoholic fatty liver disease Sleep apnea Cardiovascular Disease (MI, PVD, Stroke) Cancer (Breast, Prostate, Colorectal, Liver)