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Hyperlipidemia

The document discusses hyperlipidemia and the metabolic syndrome. It defines hyperlipidemia as abnormal lipid levels in the blood and metabolic syndrome as a clustering of conditions including obesity, high blood pressure, and abnormal cholesterol and blood sugar levels. The document outlines the causes, effects, diagnosis, and treatment of hyperlipidemia as well as the diagnostic criteria and resulting conditions of metabolic syndrome.

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Hyperlipidemia
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.
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
Atherosclerosis
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
Dietary sources of Cholesterol Type of Fat Main Source Effect on Cholesterol levels Monounsaturated Olives, olive oil, canola oil, peanut oil, Lowers LDL, Raises cashews, almonds, peanuts and most HDL other nuts; avocados Polyunsaturated Corn, soybean, safflower and cottonseed Lowers LDL, Raises oil; fish HDL Saturated Whole milk, butter, cheese, and ice cream; Raises both LDL and red meat; chocolate; coconuts, coconut HDL milk, coconut oil , egg yolks, chicken skin Trans Most margarines; vegetable shortening; Raises LDL partially hydrogenated vegetable oil; deep- fried chips; many fast foods; most commercial baked goods
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
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)
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.
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
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)
Determining Goal LDL  CHD and CHD Risk Equivalents:  Peripheral Vascular Disease  Cerebral Vascular Accident  Diabetes Mellitus
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
Treatment of Hyperlipidemia  Lifestyle modification  Low-cholesterol diet  Exercise
Medications for Hyperlipidemia Drug Class Agents Effects (% change) Side Effects HMG CoA reductase Lovastatin ↓LDL (18-55),↑ HDL (5-15) Myopathy, increased liver inhibitors Pravastatin enzymes ↓ Triglycerides (7-30) Cholesterol Ezetimibe ↓ LDL( 14-18), ↑ HDL (1-3) Headache, GI distress absorption inhibitor ↓Triglyceride (2) Nicotinic Acid ↓LDL (15-30), ↑ HDL (15-35) Flushing, Hyperglycemia, ↓ Triglyceride (20-50) Hyperuricemia, GI distress, hepatotoxicity Fibric 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
OBESITY 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
Classification of Overweight and 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
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-HT Peripheral signals Peripheral organs Glucose Gastrointestinal CCK, GLP-1, tract − Apo-A-IV Vagal afferents Food Insulin Intake + Ghrelin Adipose − Leptin tissue + Cortisol Adrenal glands
Medical Complications of Obesity Pulmonary disease abnormal function obstructive sleep apnea Stroke hypoventilation syndrome Cataracts CHD Nonalcoholic fatty liver disease Diabetes steatosis Dyslipidemia steatohepatitis Hypertension cirrhosis 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
Weight Loss Strategies  Diet therapy  Increased Physical Activity  Pharmacotherapy  Behavioral Therapy  Surgery  Any combination of the above 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 calories Atleast 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
Surgery  Roux-en-Y gastric bypass.  Lap band procedure Criteria: 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
Metabolic Syndrome Symposium
Other Names Used:  Syndrome X  Cardiometabolic Syndrome  Cardiovascular Dysmetabolic Syndrome  Insulin-Resistance Syndrome  Metabolic Syndrome
Clustering of Components:  Hypertension  Hypertriglyceridemia  Low HDL-cholesterol  Obesity (central)  Impaired Glucose Handling  Microalbuninuria (WHO)
Hypertension:  IDF:  BP >130/85 or on Rx for previously Dxed hypertension  WHO:  BP >140/90  NCEP ATP III:  BP >130/80
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
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)
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
Necessary Criteria to Make Diagnosis:  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
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)