Lipids Board Review Ira Goldberg, MD New York University School of Medicine 1. A 22 year old male college student is referred for severe hypertriglyceridemia ( 1500 mg/dl [ 17.0 mmol/l]). He has a history of pancreatitis. Height is 67 in (170.2 cm), and weight is 185 lb (84.1 kg) (BMI = 29 kg/m 2 ). He reports that much of this weight gain has occurred in the past 3 years, as he weighed 145 lb (65.9 kg) when he graduated from high school. Question 1 (1/1) Which of the following is the most important immediate lifestyle change to recommend? A. Avoid omega 3 saturated fats B. Reduce intake of noncomplex carbohydrates C. Avoid alcohol D. Drink more fruit juice E. Reduce intake of fried foods 1% 1 6 1% 1 2. A 41 year old woman with a 2 year history of infertility is noted to have a triglyceride concentration of 450 mg/dl (5.08 mmol/l). Her physicians are concerned that her induction cycle will lead to more marked hypertriglyceridemia and risk for pancreatitis. Her height is 65 in (165.1 cm), and weight is 168 lb (76.4 kg) (BMI = 28 kg/m 2 ). Question 1 Question 2 (1/1) Which of the following is the best initial therapy choice? A. Lifestyle changes B. Cholestyramine C. Fibric acid D. A statin E. Fish oil Question 2 66% 11% 18% 3. A 20 year old woman from Montreal is referred to you when an episode of pancreatitis occurs after she had been prescribed oral contraceptive pills by the college infirmary. On physical examination, you note that she has eruptive xanthomas and lipemia retinalis. She relates that as a child and teen she sometimes had abdominal pain after eating fatty foods, which she learned to avoid. Question 3 (1/3) 1
Lipemia Retinalis Question 3 (2/3) Question 3 (3/3) Which of the following is the genetic etiology most likely to have caused her hypertriglyceridemia? A. Apolipoprotein CII deficiency B. Adipose triglyceride lipase deficiency C. Apolipoprotein A5 deficiency D. Lipoprotein lipase deficiency E. Hepatic lipase deficiency 78% TG and Lipases: Lipoprotein lipase (LpL) and Hepatic lipase (HL) Hydrocarbon tail LpL O C O Glycerol O O C O O C Hydrocarbon tail Hydrocarbon tail Question 3 Lipolysis Regulation TG-triglyceride, CE-cholesteryl ester ENDOTHELIAL CELL 4. A 30 year old woman without diabetes mellitus has acute pancreatitis and a triglyceride level greater than 5000 mg/dl ( 56.50 mmol/l). She is admitted to the hospital and is treated with supportive care as is recommended for all cases of pancreatitis. Question 4 (1/1) 2
Which of the following is an additional therapy that could be used as a method to reduce liver production of triglycerides in this patient? A. Insulin and glucose B. Atorvastatin C. Heparin D. Androgen E. Metformin Question 4 86% 6% 5. You are referred a 48 year old man with a 12 year history of coronary artery disease and multiple hospitalizations for coronary artery stent placements. The patient s family has a strong history of heart disease: his father and 2 paternal uncles died before age 50 years. The patient takes atorvastatin, 80 mg daily. Total cholesterol = 210 mg/dl (5.44 mmol/l) LDL cholesterol = 150 mg/dl (3.89 mmol/l) HDL cholesterol = 40 mg/dl (1.04 mmol/l) Triglycerides = 100 mg/dl (1.13 mmol/l) Question 5 (1/1) On physical examination, you should look for which of the following findings? A. Lipemia retinalis B. Achilles xanthomas C. Eruptive xanthomas D. Palmar xanthomas E. Arthropathy 57% 1 1 Question 5 6. You are referred a 42 year old man with a family history of familial hypercholesterolemia and a recent myocardial infarction. While on rosuvastatin, 40 mg daily, and adhering to a low fat, low cholesterol diet, his LDL cholesterol concentration is 150 mg/dl (3.89 mmol/l). Because recent clinical trials reported no benefit of niacin and ezetimibe in statin treated patients, his primary care physician discontinued these 2 medications. While taking niacin and ezetimibe, his LDL cholesterol concentration was below 100 mg/dl ( 2.59 mmol/l). You elect to restart niacin and ezetimibe. You explain that the aforementioned trial results do not apply to him because of which of the following? A. His diet is optimal B. He will take a different formulation of niacin than was used in the trials C. His baseline LDL cholesterol level is different from the average baseline level in the trials D. Coronary intervention has changed since the positive trials with niacin took place E. His microbiome differs from that of 30 years ago 9 Question 6 (1/1) Question 6 3
LOW CHOLESTEROL Progression Regression HIGH 7. You are referred a 58 year old woman who has the physical finding shown in the photograph. She has been in good health and has no personal or family history of vascular disease. Moreover, she is unaware of having a dyslipidemia and is sure that her cholesterol was checked when she was younger. After menopause, she gained 20 lb (9.1 kg), and during the past year she has attempted to reduce her weight with a high fat, lowcarbohydrate diet. On this diet, her BMI has decreased from 35 to 27 kg/m 2. Her total cholesterol concentration has increased to greater than 600 mg/dl ( 15.54 mmol/l) with an equal increase in triglycerides. Thyroid function is normal. Question 7 (1/2) To make the definitive diagnosis of this patient s disorder, you should order which of the following tests? A. Apolipoprotein AI radioimmunoassay B. Apolipoprotein E radioimmunoassay C. Assessment of LDL particle size D. Apolipoprotein E genotyping E. Lipoprotein(a) gene analysis 8% 1 1 38% 2 Question 7 (2/2) Question 7 Apolipoproteins Liver ApoB100 MTTP VLDL Lipids Intestine Dietary Lipids ApoB48 MTTP Protein components of lipoprotein Functions include: serving as membrane stabilizers and cofactors for enzyme activation; interacting with receptors to promote lipid metabolism Four major classes: A, B, C, and E IDL VLDL TG/CE VLDL TG/CE Lipoprotein lipase LDL Receptor Chylomicrons TG/RE/CE Chylomicron Remnants RE/CE LDL Liver Heart 4
8. A 48 year old woman with cardiovascular disease and a 10 year history of type 2 diabetes mellitus is referred by her internist for more intensive lipid lowering therapy. While on her current regimen of atorvastatin, 80 mg daily, she has recently required a stent for a new right coronary artery occlusion. On metformin and once daily, long acting insulin, her hemoglobin A 1c level is less than 7% ( 0.070). During the past 3 years, the patient has gained 30 lb (13.6 kg). Question 8 (1/2) Total cholesterol = 160 mg/dl (4.14 mmol/l) Triglycerides = 300 mg/dl (3.39 mmol/l) HDL cholesterol = 35 mg/dl (0.91 mmol/l) LDL cholesterol = 65 mg/dl (1.68 mmol/l) Non HDL cholesterol = 125 mg/dl (3.24 mmol/l) In addition to encouraging exercise and weight loss, you recommend fenofibrate as an approach to reduce her non HDL cholesterol. Question 8 (2/2) Which of the following might be the additional benefit of fenofibrate treatment in this patient with type 2 diabetes? A. Decreased hemoglobin A 1c level B. Decreased proteinuria C. Decreased retinopathy D. Decreased blood pressure E. Increased insulin sensitivity 1 46% 3 Comparison of ACCORD Subgroup Results With Those From Previous Fibrate Studies Trial (Drug) Primary Endpoint: Entire Cohort (P value) HHS (Gemfibrozil) -3 (.02) Lipid Subgroup Criterion Primary Endpoint: Subgroup TG >200 mg/dl LDL-C/HDL-C >5.0-71% (0.005) BIP (Bezafibrate) -7. (.24) TG >200 mg/dl -39. (0.02) FIELD (Fenofibrate) -11% (.16) TG >204 mg/dl HDL-C <42 mg/dl -27% (0.005) ACCORD (Fenofibrate) -8% (.32) TG >204 mg/dl HDL-C <34 mg/dl -31% Question 8 9. A 50 year old man with type 2 diabetes mellitus has a hemoglobin A 1c level of 7.8% (0.078) and is currently treated with rosuvastatin, 40 mg daily. His other risk factor for cardiovascular disease is hypertension. Total cholesterol = 185 mg/dl (4.79 mmol/l) LDL cholesterol = 120 mg/dl (3.11 mmol/l) HDL cholesterol = 45 mg/dl (1.17 mmol/l) Triglycerides = 100 mg/dl (1.13 mmol/l) Question 9 (1/1) Which of the following added cholesterolreducing therapies also might assist with his glucose control? A. Niaspan B. Colesevelam C. Pitavastatin D. Ezetimibe E. Anacetrapib Question 9 8 5
10. A 52 year old woman with familial hypercholesterolemia has been treated with rosuvastatin, 40 mg daily, and ezetimibe, 10 mg daily, for the past 5 years. This combination has reduced her total cholesterol concentration from 385 to 215 mg/dl (9.97 to 5.57 mmol/l) and her LDL cholesterol concentration from 300 to 120 mg/dl (7.77 to 3.11 mmol/l). She now presents with a total cholesterol concentration of 260 mg/dl (6.73 mmol/l) and reports muscle pains. Creatine phosphokinase and blood glucose levels are not elevated. Question 10 (1/1) Which of the following tests would be most useful? A. Dexamethasone suppression B. FSH measurement C. TSH measurement D. Urinary protein measurement E. Prolactin measurement Question 10 88% 7% 11. A 45 year old woman with rheumatoid arthritis is referred for hypercholesterolemia and statin induced myalgia; creatine kinase has never been documented to be elevated. Her physician has tried treating her with simvastatin, atorvastatin, and rosuvastatin. Which of the following is the best next step in this patient s care? A. Treat with a statin plus coenzyme Q10 B. Treat with rosuvastatin once weekly C. Measure lipoprotein(a) D. Treat with fish oil E. Assess for statin antibodies 37% 48% Question 11 (1/1) Question 11 12. A 31 year old man with type 2 diabetes mellitus treated with metformin, pioglitazone, atorvastatin, and fenofibrate is referred for the following lipid panel: HDL cholesterol = 5 mg/dl (0.13 mmol/l) LDL cholesterol = 120 mg/dl (3.11 mmol/l) Triglycerides = 300 mg/dl (3.39 mmol/l) On a previous lipid profile 5 years ago, his HDLcholesterol level was 25 mg/dl (0.65 mmol/l). His BMI is 37 kg/m 2, and his hemoglobin A 1c level is 6.3 (0.063). Question 12 (1/1) This marked reduction in HDL cholesterol is most likely due to which of the following? A. Acquired lecithin cholesterol acyltransferase deficiency B. Fenofibrate therapy C. Statin induced hypoalphalipoproteinemia D. Metformin inhibition of ABCA1 E. Erroneous apolipoprotein B precipitation Question 12 3 2 26% 6% 1 6
Causes of Low HDL Cholesterol Hypertriglyceridemia Obesity Insulin resistance Anabolic steroids Rare genetic disorders: LCAT deficiency, apo A I deficiency, ABCA I deficiency, vanishing HDL syndrome due to inflammation 13. A 30 year old woman with a 20 year history of type 1 diabetes mellitus currently treated with an insulin pump is referred to you for advice regarding hypercholesterolemia. Her BMI is 22 kg/m 2. She exercises regularly and maintains a low saturated fat, low cholesterol diet. Aside from insulin, her only other medication is an oral contraceptive. Hemoglobin A 1c = 6.1% (0.061) Total cholesterol = 280 mg/dl (7.25 mmol/l) HDL cholesterol = 110 mg/dl (2.85 mmol/l) LDL cholesterol = 155 mg/dl (4.01 mmol/l) Triglycerides = 75 mg/dl (0.85 mmol/l) Question 13 (1/1) Which of the following should you recommend? A. Continue to rely on lifestyle interventions B. Add fish oil C. Discontinue the oral contraceptive therapy D. Add atorvastatin E. Add colesevelam Question 13 2 36% 36% Osler 1892 Osler s Observations on Diabetes Page 295. It is a disease of adult life. It is a disease of higher classes. The subjects have been excessively fat. More common in cities than in country districts. Hebrews seem especially prone to it. Page 297. The heart shows no characteristic changes The Principles and Practice of Medicine, 1892 14. A 27 year old man is referred to you because of low blood cholesterol levels. Total cholesterol = 56 mg/dl (1.45 mmol/l) HDL cholesterol = 24 mg/dl (0.62 mmol/l) LDL cholesterol = 24 mg/dl (0.62 mmol/l) Triglycerides = 38 mg/dl (0.43 mmol/l) BMI is 24 kg/m 2. He has no obvious medical conditions. You provide him with advice on lifestyle. Which of the following do you advise him is one possible complication from his condition? A. Coronary artery disease B. Nonalcoholic fatty liver disease C. Renal failure D. Tonsillitis E. Myositis 1 51% 1 1 Question 14 (1/1) Question 14 7
15. You are referred a 30 year old woman with systemic lupus erythematosus and the following lipid profile: Total cholesterol = 300 mg/dl (7.77 mmol/l) HDL cholesterol = 30 mg/dl (0.78 mmol/l) Triglycerides = 1000 mg/dl (11.30 mmol/l) LDL cholesterol cannot be estimated. Her current medications include prednisone, 20 mg daily; hydrochlorothiazide; lisinopril and metoprolol for hypertension; and infliximab. Question 15 (1/1) You are concerned that medications could be contributing to her dyslipidemia. You recommend which of the following adjustments? A. Switch prednisone to dexamethasone B. Switch metoprolol to amlodipine C. Switch infliximab to gold therapy D. Switch hydrochlorothiazide to chlorthalidone E. Discontinue lisinopril Question 15 48% 17% 26% 16. You are consulted about 60 year old man in the medical intensive care unit who has been on a respirator for 3 weeks and is recovering from a communityacquired pneumonia. The patient is cachectic. He is not hypotensive. His electrolytes are normal, and his albumin level is 2.0 g/dl (20 g/l). His glucose concentration is 147 mg/dl (8.16 mmol/l) and he is being treated with insulin. His total cholesterol level is 90 mg/dl (2.33 mmol/l), and the attending physicians are concerned that this could lead to adrenal insufficiency. A cosyntropin stimulation test reveals a baseline cortisol concentration of 4 g/dl (110.4 nmol/l) and stimulation to 17 g/dl (469.0 nmol/l). Question 16 (1/1) Which of the following is the most likely reason for this test result? A. Abetalipoproteinemia B. Acquired hypocholesterolemic cortisol deficiency C. Normal stimulation, but baseline adrenal insufficiency D. Cortisol binding globulin deficiency E. Hypothalamic/pituitary insufficiency Question 16 6% 7% 77% 17. You see a 55 year old man who is anxious about his cardiovascular risk. He exercises regularly; has a blood pressure of 115/65 mm Hg; and avoids high fat, high cholesterol foods. His father was a World War II veteran who smoked 2 packs of cigarettes daily until having a myocardial infarction at age 62 years. Total cholesterol = 190 mg/dl (4.92 mmol/l) LDL cholesterol = 105 mg/dl (2.72 mmol/l) HDL cholesterol = 70 mg/dl (1.81 mmol/l) Triglycerides = 75 mg/dl (0.85 mmol/l) Question 17 (1/1) Which additional test could you order to best assess this man s cardiovascular disease risk? A. Coronary calcium score B. LDL particle size distribution C. Apolipoprotein B by immunoassay D. Antioxidant levels E. Serum palmitate measurement Question 17 8 7% 8
18. A gastroenterologist refers to you a 28 year old woman with primary biliary cirrhosis. During her workup, the gastroenterologist noted that her total cholesterol level was 450 mg/dl (11.66 mmol/l). In this situation, her cholesterol elevation is associated with an increase in which lipidcontaining particle? A. Lipoprotein X B. Lipoprotein(a) C. Small, dense LDL D. Retinal binding protein 4 E. HDL 4 3 16% Question 18 (1/1) Question 18 19. You are asked to see a 35 year old Japanese American woman with the following lipid panel: Total cholesterol = 245 mg/dl (6.35 mmol/l) LDL cholesterol = 110 mg/dl (2.85 mmol/l) HDL cholesterol = 120 mg/dl (3.11 mmol/l) Triglycerides = 75 mg/dl (0.85 mmol/l) Which of the following is the most likely cause of this lipoprotein profile? A. Cholesterol ester transfer protein (CETP) deficiency B. Lecithin cholesterol acyltransferase (LCAT) deficiency C. Hepatic lipase deficiency D. Scavenger receptor B1 (SR B1) deficiency E. ABCA1 deficiency 6 1 8% 7% Question 19 (1/1) Question 19 20. You are referred a patient with HIV infection who is currently treated with a protease inhibitor and antiviral medications. He has developed mild lipoatrophy and his lipid panel is as follows: Total cholesterol = 280 mg/dl (7.25 mmol/l) LDL cholesterol = 180 mg/dl (4.66 mmol/l) HDL cholesterol = 30 mg/dl (0.78 mmol/l) Triglycerides = 350 mg/dl (3.96 mmol/l) You start treatment with atorvastatin, 10 mg daily, and his LDL cholesterol level decreases to 120 mg/dl (3.11 mmol/l). Which of the following is most likely to occur and prevent the use of a higher statin dosage in this patient? A. Diabetes mellitus B. Myositis C. Inhibition of antiviral agents D. Negative interaction with antibiotics E. Hepatitis 6 28% 8% Question 20 (1/1) Question 20 9