Lipids 101 Cardiology Board Review Med-Peds Style!

Therapeutic Lifestyle Changes (TLC) Drug CHD and CHD Risk Equivalents year risk >20% 2+ Risk Factors year risk 10–20% 2+ Risk Factors year risk <10% 0–1 Risk Factor Total65.3M 36.5M Americans requiring treatment for Hyperlipidemia

Inherited Dyslipidemias

Metabolic Syndrome Abdominal obesity (>40” in men; >35” in women Atherogenic dyslipidemia –Elevated triglycerides (>150mg/dl) –High LDL –Low HDL (<40 in men; <50 in women) Raised blood pressure (>130/85) Insulin resistance (  glucose intolerance) –Fasting glucose >110mg/dl Prothrombotic state Proinflammatory state 3 Orange Criteria = Diagnosis!

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 LDL Goal (mg/dL) LDL to Initiate Therapeutic Lifestyle Changes (TLC) (mg/dL) LDL to Consider Drug Therapy (mg/dL) CHD or CHD Risk Equivalents (10-year risk  20%) <100  100  130 (100–129: drug optional) 2+ Risk Factors (10-year risk  20%) <130  year risk 10– 20%:  year risk <10%:  160 0–1 Risk Factor<160  160  190 (160–189: LDL- lowering 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 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 If LDL goal not achieved, Consider higher dose of statin or add a bile acid sequestrant or nicotinic acid If LDL goal not achieved, intensify drug therapy or refer to a lipid specialist If LDL goal achieved, treat other lipid risk factors MONITORMONITOR 6 wks Q 4-6 mo Start statin or bile acid sequestrant or nicotinic acid AFTER 3 MONTHS OF TLC

Classification of Serum Triglycerides Normal <150 mg/dL Borderline high150–199 mg/dL High200–499 mg/dL Very high  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