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Hyperlipidemia

Hyperlipidemia. Screening for Dyslipidemia. U.S. Preventive Services Task Force (USPSTF) guidelines: Strongly recommends screening men age 35 or older for lipid disorders Recommends screening men age 20-35 if they are at increased risk for coronary heart disease

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Hyperlipidemia

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  1. Hyperlipidemia

  2. Screening for Dyslipidemia • U.S. Preventive Services Task Force (USPSTF) guidelines: • Strongly recommends screening men age 35 or older for lipid disorders • Recommends screening men age 20-35 if they are at increased risk for coronary heart disease • Strongly recommends screening women over age 45 with CHD risk factors • Recommends screening women age 20-45 if they are at increase risk for coronary heart disease • No recommendation on screening men age 20-35 or women older than age 20 who are not at increased risk for CHD • The optimal interval for screening is uncertain

  3. Secondary causes of dyslipidemia • Cigarette smoking • Modestly lowers HDL and may induce insulin resistance • Obesity • Increased Total cholesterol, Triglycerides, LDL, and decreased HDL • Medications • Thiazides and Beta blockers may cause small changes in lipid profile • Atypical antipsychotics may cause weight gain and hypertriglyceridemia • Protease inhibitors are associated with abnormalities in lipid metabolism

  4. ATP III Guidelines • Based upon epidemiologic data that showed a relationship between total cholesterol and coronary risk • Influenced by the absence (primary prevention) or presence (secondary prevention) of preexisting CHD

  5. Risk Assessment • Obtain a fasting lipid profile • Identify the presence of CHD risk equivalents • Identify the presence of other major CHD risk factors • If 2 or more risk factors are present in a patient without CHD risk equivalents, calculate 10-year risk of CHD • Determine the risk category that establishes the LDL goal, when to start lifestyle mods, and when to consider drug therapy

  6. Risk Assessment • CHD Equivalents • Diabetes Mellitus • Symptomatic carotid artery disease • Peripheral arterial disease • Abdominal aortic aneurysm • Multiple risk factors that confer a 10-year CHD risk of >20% • Chronic renal insufficiency (GFR<60)??

  7. Risk Assessment • Other risk factors • Cigarette smoking • Hypertension (BP>140/90 or on anti-hypertensives) • HDL cholesterol <40mg/dl • Family hx of premature CHD (male first degree relatives <55 y/o or female <65y/o) • Age (men >45 y/o or women >55 y/o)

  8. Risk Assessment • Risk does not need to be calculated in people without CHD (or equivalents) who have 0-1 risk factors • If person without CHD (or equivalent) has 2 or more risk factors, use the ATP III modification of the Framingham risk tables to calculate 10-year risk of CHD

  9. The First Intervention • Therapeutic Lifestyle Changes (TLC) • TLC diet • Increase physical activity • Consider referral to Nutritionist/Dietician • Reassess Lipid panel in 6 weeks • Increase plant sterols • Increase dietary fiber • Nutritionist/Dietician if haven’t already • Re-reassess Lipids in 6 weeks

  10. HMG CoA Reductase Inhibitors • Competitive inhibitors of HMG CoA reductase, the rate-limiting step in cholesterol biosynthesis • Majority of cholesterol synthesis appears to occur at night • Recommended that statins be administered in the evening or at bedtime • LDL decrease 18 – 55% • HDL increase 5 – 15% • Triglycerides decrease 7 – 30% • Side effects include hepatic dysfunction, muscle injury

  11. HMG CoA Reductase Inhibitors

  12. HMG CoA Reductase Inhibitors • Hepatic dysfunction • 0.5-3% risk of persistent elevations in aminotransferase levels • Dose dependent, occurs primarily in first three months of treatment • Get LFT’s before and 12 weeks after starting statin and after dose elevations • If ALT is >3 times upper limit of normal (on two different lab draws), recommend changing medication or lowering dose

  13. HMG CoA Reductase Inhibitors • Muscle Injury • Myalgia->Myositis->Rhabdomyolysis • Approx 2-11% risk of myalgias, don’t always see elevation in CPK levels • Muscle sx’s usually begin weeks to months after starting statin • Increased risk with statins metabolized by cytochrome P-450 3A4 (lovastatin, simvastatin, atorvastatin) and concurrent therapy with other drugs (or breakfast juices) that interfere with CYP3A4 • Isoniazid, Clarithromycin, Fluconazole, Ketoconazole, Diltiazem, Erythromycin, Grapefruit juice

  14. HMG CoA Reductase Inhibitors • Muscle Injury (cont.) • Also higher risk in patients with acute or chronic renal failure, obstructive liver disease, and hypothyroidism • Useful to obtain a CPK level prior to starting statin therapy, although serial monitoring of CPK’s are problematic • Better to have your patients tell you if they have any symptoms consistent with muscle toxicity • Pravastatin and Fluvastatin seem to have lower risk, may be reasonable to try one of these for patients who don’t tolerate other statins

  15. HMG CoA Reductase Inhibitors • Pregnancy category X • Long-term safety data are lacking • Also uncertain whether long-term statin therapy leads to better outcomes compared with delaying treatment until patients have a higher CHD risk

  16. Bile Acid Sequestrants • Cholestyramine, Colestipol • LDL decrease 15 – 30% • HDL increase 3 – 5% • Triglycerides may increase • Side effects include nausea, bloating, cramping, constipation, elevated LFTs, and decreased absorption of other drugs • Don’t use if baseline hypertriglyceridemia

  17. Niacin • LDL decrease 5 – 25% (~3 g/d) • HDL increase 15 – 35% (~1 – 1.5 g/d) • Triglycerides decrease 20 – 50% • Side effects include flushing, pruritis, paresthesias, nausea, hepatotoxicity, hyperglycemia, hyperuricemia, increased homocysteine

  18. Fibric Acid Derivatives • Gemfibrozil, Fenofibrate • LDL decrease up 5 – 20% • May increase in pts with high triglycerides • HDL increase 10 – 20% • Triglycerides decrease 20 – 50% • Side effects include myopathy, gallstones, GI upset. Need to adjust for renal disease. • Fenofibrate is the preferred fibrate when patient is also on a statin medication • Gemfibrozil increases risk of statin muscle toxicity

  19. Ezetimibe (Zetia) • Inhibits absorption of cholesterol at the brush border of the small intestine • Added to statins • Additional 25% decrease in LDL • Additional 14% decrease in triglycerides • Slight increase in HDL • No significant side effects or drug interactions

  20. Omega-3 Fatty Acids (Fish Oil) • Generally requires large doses (2–6 gms tid) • LDL may increase variably (modest effect) • HDL increase ~5% (variable) • Triglycerides decrease 50% • Side effects include nausea, bloating, flatulence, diarrhea, fishy taste and odor, weight gain

  21. Plant Sterol-Containing Margarines • “Promise Activ” (Sitosterol, Campesterol) • “Benecol” (Sitostanol, Campestanol) • Plant sterols with structure similar to cholesterol; may inhibit cholesterol absorption • LDL decrease 13 – 20% with 3-5 grams/day • No significant change in HDL or triglycerides • Have not been evaluated for clinical end points

  22. Red Yeast Rice • Fermented rice product • Contain monacolins, naturally occurring substances that have HMG CoA reductase inhibitor activity • Monacolin K is the active ingredient in Lovastatin • 2.4 gram/day of Red Yeast Rice is equivalent to 4.8mg Lovastatin • Many different preparations and no standardization

  23. Starting Drug Therapy • Can start with statin at low-moderate doses that have been used in clinical trials • Pravastatin 40mg • Atorvastatin 10mg • Can also start with a moderately higher dose of a statin • Simvastatin 40mg • Atorvastatin 20mg • No studies have directly compared effects of low-moderate intensity tx with high-intensity tx for primary prevention • Get LFT’s and consider baseline CPK as previously discussed

  24. Managing Statin Side Effects • Muscle pain or elevated CPK • Reasonable to stop statin and re-challenge later with lower dose or different statin • Elevated ALT • <3 times upper limit of normal and asymptomatic • Reasonable to continue statin and monitor serial LFT’s and for development of symptoms • >3 times upper limit of normal and asymptomatic • Reasonable to stop statin, see if ALT resolves, and re-challenge with lower dose or different statin • May also continue statin at lower dose, or change to different statin

  25. What if patient is not at goal LDL? • Reemphasize importance of Therapeutic Lifestyle Changes • Increase dose of statin • Inefficient, doubling of dose only decreases LDL by another 6-7% • Change statin • Atorvastatin is strongest formulary statin • Add low dose bile acid sequestrant • Can give another 10% decrease in LDL • Add Zetia • Add Niacin • Add plant sterol-containing margarine

  26. Metabolic Syndrome • A constellation of lipid and non-lipid risk factors of metabolic origin • Closely linked with insulin resistance, where the normal actions of insulin are impaired • Diagnosis is made when 3 or more risk factors are present

  27. Metabolic Syndrome • Metabolic syndrome risk factors increase CHD risk at any LDL-level • A secondary target of therapy after LDL control • Management has two objectives • Reduce underlying causes (obesity, inactivity) • Treat associated nonlipid and lipid risk factors • First-line therapies for all risk factors associated with the metabolic syndrome are weight reduction and increased physical activity • If LDL is controlled and metabolic syndrome is present, TLC should stress weight reduction and physical activity

  28. Specific Dyslipidemias • Very High LDL (>190 mg/dl) • Usually genetic • Recommend family testing • Often need combined treatment to reach LDL goal (statin plus bile acid sequestrant)

  29. Hypertriglyceridemia • An independent risk factor for CHD • Accumulation of triglyceride-rich lipoproteins (chylomicrons, VLDL, partially degraded VLDL, and IDL) in plasma • Chylomicrons and large VLDL are less atherogenic • Small VLDL is more atherogenic • VLDL cholesterol is easiest way to measure atherogenic remnant lipoproteins

  30. Hypertriglyceridemia • Since triglyceride-rich lipoproteins also transport cholesterol, hypercholesterolemia often accompanies hypertriglyceridemia • Contributing factors to hypertrig

  31. Hypertriglyceridemia

  32. Borderline High Trigs • 150-199 mg/dl • Emphasize TLC, particularly weight loss and exercise

  33. High Trigs • High (200-499 mg/dl) • Non-HDL (LDL + VLDL) becomes a secondary target of therapy • Want non-HDL to be less than 30 mg/dl higher than LDL • Goal VLDL <30 mg/dl • Statins have less VLDL lowering effect • May add Niacin or a fibrate (Fenofibrate is best choice with statin therapy)

  34. Very High Trigs • >500 mg/dl • Goal is to prevent pancreatitis • TLC and Fibrate or Niacin

  35. Isolated Hypertriglyceridemia • With low LDL and/or low HDL • May use drug therapy if TLC doestn’t work and patient has a strong family history of CHD or multiple risk factors • Fibrates are probably the best choice • May add Niacin • Consider Fish Oil

  36. Questions?

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