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Lipids 101 Cardiology Board Review Med-Peds Style! Americans requiring treatment for Hyperlipidemia CHD and CHD Risk Equivalents 10-year risk >20% Therapeutic Lifestyle Changes (TLC) 24.1 Drug 20.7 29 35 2+ Risk Factors 10-year risk 10–20% 10.9 8.3 2+ Risk Factors 10-year risk <10% 14.6 2.8 30.2 0–1 Risk Factor 15.6 Total 7.5 4.7 65.3M 36.5M Inherited Dyslipidemias Disease Phe noty pe Abnorma l Lipid Def ect Familial Hyperchole st er ole mia II a Familial l ipopr ot ein l ipase def iciency I, V Familial Hypertri gl yc er idemia Comb ined Hyp er lipidemia I, V VLDL Unknown I ib VLDL, LDL Unknown Familial dysb eta lipopr ot eine mia III VLDL Def ect ive or abs ent apo- E Leciti hin- chole st er ol acet yl tran sf era se def iciency Tan gier disease N/A HDL Rapid ap o- A- 1 catab olism N/A HDL Rapid HDL c atab olism LDL Def ect in LDL r ecept or or ap o- B100 may be he ter ozygous o r homozygous chylo micr ons Lipoprot ein L ipase def iciency Clinic al p re se ntat ion Tendinous xa nt homas, Xant hel asm a, Planar xa nt homas Cor ne al ar cus Risk of CHD +++ Eru pt ive xant homa s, Lipemia r eti nalis, Abdominal Pa in, Hepa t o- splen omegaly Oft en as ympt oma t ic 0 Oft en as ympt oma t ic e xcept CHD, Yell ow- ora nge palmar cr ease s Tub er oer upti ve xa nt homas, Hyperur icemia, Glu cose int oleran ce, Cor neal opacit ie s Renal insuff iciency, H emolyt ic anemia +++ Cor ne al opa cit ie s, polyne ur opat hy, ora nge t onsils 0 + +++ + Metabolic Syndrome • Abdominal obesity (>40” in men; >35” in women 3 Orange • Atherogenic dyslipidemia – Elevated triglycerides (>150mg/dl) – High LDL – Low HDL (<40 in men; <50 in women) Criteria = Diagnosis! • Raised blood pressure (>130/85) • Insulin resistance ( glucose intolerance) – Fasting glucose >110mg/dl • Prothrombotic state • Proinflammatory state Risk Assessment • Measure fasting LDL in all patients beginning at age 20yo. • For patients with multiple (2+) risk factors – Recheck LDL every 5 years • For patients with 0–1 risk factor – 5 year risk assessment not required – Most patients have 10-year risk <10% Major Risk Factors (Exclusive of LDL) That Modify LDL Goals • Cigarette smoking • Hypertension (BP 140/90 mmHg or on antihypertensive medication) • Low HDL cholesterol (<40 mg/dL)† • Family history of premature CHD – CHD in male first degree relative <55 years – CHD in female first degree relative <65 years • Age (men 45 years; women 55 years) CHD Risk Equivalents • Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease) • Diabetes (10-year risk for CHD =20%) • Multiple risk factors that confer a 10-year risk for CHD >20% Lifestyle Risk Factors • Obesity (BMI 30) • Physical inactivity • Atherogenic diet Causes of Secondary Dyslipidemia • • • • • Diabetes Hypothyroidism Obstructive liver disease Chronic renal failure Drugs that raise LDL cholesterol and lower HDL cholesterol (progestins, anabolic steroids, and corticosteroids) Primary Prevention With LDL-Lowering Therapy Public Health Approach • Reduced intakes of saturated fat and cholesterol • Increased physical activity • Weight control Secondary Prevention With LDL-Lowering Therapy • Benefits: reduction in total mortality, coronary mortality, major coronary events, coronary procedures, and stroke • LDL cholesterol goal: <100 mg/dL • Includes CHD risk equivalents • Consider initiation of therapy during hospitalization (if LDL 100 mg/dL) LDL Goals and Cutpoints for Therapeutic Lifestyle Changes (TLC) and Drug Therapy Risk Category CHD or CHD Risk Equivalents (10-year risk 20%) 2+ Risk Factors (10-year risk 20%) 0–1 Risk Factor LDL Goal (mg/dL) <100 <130 LDL to Initiate Therapeutic Lifestyle Changes (TLC) (mg/dL) LDL to Consider Drug Therapy (mg/dL) 100 130 (100–129: drug optional) 130 10-year risk 10– 20%: 130 10-year risk <10%: 160 <160 160 190 (160–189: LDLlowering drug optional) July 14, 2004: NCEP updated stratified cholesterol guidelines Very high risk individuals: patients with CAD AND DM, uncontrolled HTN, or metabolic risk factors including obesity, high triglycerides, and low HDL. Smokers with CAD. Goal of therapy--LDL < 70 mg/dl High-risk individuals: CAD or DM or multiple risks factors -- Goal of therapy-LDL < 100 mg/dl July 14, 2004: NCEP updated stratified cholesterol guidelines Moderately high risk: Multiple risk factors for CAD with a 10% to 20% chance of having an MI or cardiac death within a decade. If the LDL level is between 100-129 mg/dl then a statin drug may be started. Goal of therapy--LDL < 100 mg/dl Lower or moderate risk: Dietary changes and exercise unless LDL levels are very high LDL-Lowering Therapy…How low do we go? Baseline LDL: <100 mg/dL • Further LDL lowering not required except in CHD and CHD risk equivalent then use LDL <70 • Therapeutic Lifestyle Changes (TLC) • Consider treatment of other lipid risk factors – Elevated triglycerides – Low HDL cholesterol HMG CoA Reductase Inhibitors (Statins) • Reduce LDL-C 18–55% & TG 7–30% • Raise HDL-C 5–15% • Major side effects – Myopathy – Increased liver enzymes • Contraindications – Absolute: liver disease – Relative: use with certain drugs Bile Acid Sequestrants Cholestyramine, Colestipol, Colesevelam • Major Actions – Reduce LDL-C 15–30% – Raise HDL-C 3–5% – May increase TG • Side effects – GI distress/constipation – Decreased absorption of other drugs • Contraindications – Dysbetalipoproteinemia – Raised TG (especially >400 mg/dL) Nicotinic Acid • Major actions – Lowers LDL-C 5–25% – Lowers TG 20–50% – Raises HDL-C 15–35% • Side effects: flushing, hyperglycemia, hyperuricemia, upper GI distress, hepatotoxicity • Contraindications: liver disease, severe gout, peptic ulcer Fibric Acids Gemfibrozil, Fenofibrate, Clofibrate • Major actions – Lower LDL-C 5–20% (with normal TG) – May raise LDL-C (with high TG) – Lower TG 20–50% – Raise HDL-C 10–20% • Side effects: dyspepsia, gallstones, myopathy • Contraindications: Severe renal or hepatic disease DRUG TREATMENT PLAN Start statin or bile acid sequestrant or nicotinic acid AFTER 3 MONTHS OF TLC 6 wks If LDL goal not achieved, Consider higher dose of statin or add a bile acid sequestrant or nicotinic acid 6 wks If LDL goal not achieved, intensify drug therapy or refer to a lipid specialist If LDL goal achieved, treat other lipid risk factors Q 4-6 mo M O N I T O R Classification of Serum Triglycerides • • • • Normal Borderline high High Very high <150 mg/dL 150–199 mg/dL 200–499 mg/dL 500 mg/dL 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 LDL lowering Causes of Low HDL Cholesterol (<40 mg/dL) • • • • • • • Elevated triglycerides Overweight and obesity Physical inactivity Type 2 diabetes Cigarette smoking Very high carbohydrate diet (>60%) beta-blockers, anabolic steroids, progestational agents Management of Low HDL Cholesterol • LDL cholesterol is primary target of therapy • Weight reduction and increased physical activity (if the metabolic syndrome is present) • Non-HDL cholesterol is secondary target of therapy (if triglycerides 200 mg/dL) • Consider nicotinic acid or fibrates (for patients with CHD or CHD risk equivalents) Previous In-service Topics Hyperlipidemia due to secondary causes Statin associated myositis Target LDL in DM and HTN Which statin is least likely to be metabolized by P450 and least likely to interact with anti-retrovirals. Causes of hypertriglyceridemia Food for Thought… "The average American may be fine with an LDL of 120, but when we're born we have an LDL of 25 or 30. If we put statins in the drinking water, would it help public health? Yes, but public health endeavors would help more. Our obesity epidemic needs to be conquered not with medicine but with effective change for the whole population. If you're looking at cost-effectiveness, it’s time to teach young people to eat right and exercise. We can do that -- or we can start throwing 10 medicines at them when they are 40 or 50 years old." -Lawerence S. Sperling, MD Director of Emory Heart Center Risk Reduction Program