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# Which of the following is probably the least atherogenic combination of total cholesterol and HDL in a 50-year-old man with

a triglyceride level of 260 mg/dL? A. Total cholesterol 150 mg/dL, HDL 38 mg/dL B. Total cholesterol 220 mg/dL, HDL 42 mg/dL C. Total cholesterol 200 mg/dL, HDL 40 mg/dL D. Total cholesterol 250 mg/dL, HDL 44 mg/dL E. Total cholesterol 200 mg/dL, HDL 35 mg/dL

Correct Answer: Total cholesterol 150 mg/dL, HDL 38 mg/dL The total cholesterolHDL ratio is a good predictor of coronary heart disease (CHD) risk. In persons with a triglyceride (TG) level greater than 200, however, the non-HDL is a good secondary target for therapy and should be lowered. Non-HDL cholesterol is measured as total cholesterol minus HDL. The target for non-HDL cholesterol is 30 mg/dL above the usual LDL target. In this patient, with TG of 260 mg/dL, the least atherogenic profile would be the choice with the lowest non-HDL cholesterol (Answer A, where 150 38 = 112). Also, if a person's total cholesterol is consistently less than 150 mg/dL with at least an average HDL, then his or her expected CHD risk is low.

You diagnosed a 56-year-old man with hypercholesterolemia 3 months ago. He also has hypertension and a family history of coronary heart disease. His initial cholesterol values had been total cholesterol (TC) 310 mg/dL, LDL 205 mg/dL, and HDL 35 mg/dL; you had started a statin. He has been very compliant with your recommendations about diet and exercise and has been taking the initial dose of statin drug on a regular basis. Repeat measurements of his cholesterol this visit reveal that his LDL is 156 mg/dL. Liver function is normal. Which of the following suggestions is most appropriate as a next step? A. Increase the dose of statin and recheck the liver tests in 6 months B. Increase the dose of statin and recheck the liver tests in 6 to 12 weeks C. Increase the statin and add cholestyramine to his regimen D. Increase the statin and add gemfibrozil to his regimen E. Recheck the lipid profile in 6 months, as the statin has not had adequate time to show an effect

Correct Answer: Increase the dose of statin and recheck the liver tests in 6 to 12 weeks The patient's LDL goal of less than 130 mg/dL (due to more than two cardiac risk factors) is still not met. Therefore, continued action must be taken, and waiting another 6 months is not appropriate. The best choice is to increase the dose of the current drug (statin) until this dose is maximized. If the LDL still remains high at that point, it would then be more appropriate to add a second agent. There is a higher incidence of adverse effects with gemfibrozil, but adding fenofibrate is safe. Once the dose of a statin is increased, a lipid profile and liver function tests should generally be rechecked in 6 to 12 weeks.

Which of the following medications may worsen glycemic control in a person with impaired fasting glucose? A. Fenofibrate B. Nicotinic acid C. Colestipol D. Pravastatin

Correct Answer: Nicotinic acid Niacin at high doses may tend to raise glucose and uric acid levels. Most of the time, this can be satisfactorily managed through use of another medication to improve glycemic control or adoption of better lifestyle habits. Furthermore, the benefits of improving the cholesterol profile will likely outweigh any potential detriment from a small increase in serum glucose.

A 60-year-old man with hypertension, poorly controlled diabetes mellitus, and a 50-year pack-aday smoking history has the following laboratory results: Total cholesterol: 245 mg/dL HDL: 40 mg/dL

Triglycerides: 250 mg/dL LDL: 98 mg/dL Which of the following is true? A. Control of non-HDL cholesterol is of limited value B. The primary target of therapy in this patient is triglycerides C. Fibrate monotherapy will most benefit this patient D. The patient will be a candidate for statin therapy once LDL cholesterol rises above 100 mg/dL E. Non-HDL cholesterol is a secondary target of therapy in this patient

Correct Answer: Non-HDL cholesterol is a secondary target of therapy in this patient LDL is the primary target of therapy in this patient. Once triglyceride levels surpass 200 mg/dL, following and treating the non-HDL cholesterol becomes a secondary priority. Non-HDL is calculated as total cholesterol minus HDL, and the goal is 30 mg/dL higher than the LDL goal. Triglycerides are not a primary target of therapy until levels reach 500 mg/dL. This patient has multiple major cardiac risk factors and therefore is at high risk for coronary heart disease (CHD). Treatment should be initiated at his current LDL level. Fibrate monotherapy is inferior to statin monotherapy in preventing CHD events in diabetic patients and lacks substantial mortality benefit.

A 55-year-old man with well-controlled hypertension is found to have an LDL cholesterol of 145 mg/dL and triglycerides of 175 mg/dL. He pursues diet therapy for 6 months with no improvement. You recommend A. Referral to an endocrinologist B. An additional 4 months of stricter dietary therapy to ensure an adequate trial C. Beginning drug therapy with a fibrate D. Beginning drug therapy with a statin E. Beginning both a fibrate and a statin

Correct Answer: Beginning drug therapy with a statin The patient has two risk factors for coronary heart disease: age greater than 45 years and hypertension. Therefore, his LDL goal is less than 130 mg/dL. Referral to an endocrinologist is not yet necessary. Six months of diet therapy is adequate to assess effectiveness and/or compliance. Fibrates are more effective in lowering triglycerides than LDL levels. Gemfibrozil probably should not be used in combination with statins due to the increased risk of rhabdomyolysis. Beginning statin therapy is correct.

A 45-year-old woman undergoes routine cholesterol screening in your office. She is found to have a reasonable LDL of 140 mg/dL. You advise her that which of the following, if consumed in higher than average amounts, is most likely to lead to a more atherogenic lipid profile? A. Polyunsaturated fats B. Monounsaturated fats C. Vegetable shortening D. Omega-3 fatty acids

Correct Answer: Vegetable shortening Vegetable shortening is produced by hydrogenation, which results in the production of transfatty acids that elevate cholesterol levels. Polyunsaturated and monounsaturated fats have a more beneficial effect on lipids. Omega-3 fatty acids tend to lower triglycerides and are inversely associated with cardiovascular disease.

A 58-year-old man with a strong family history of coronary heart disease is interested in lowering his risk. You check a fasting lipid profile and find the following: LDL: 150 mg/dL Triglycerides: 405 mg/dL HDL: 22 mg/dL You recommend drug therapy. Which of the following will have the least favorable effect on his triglyceride level and HDL? A.

## Cholestyramine B. Gemfibrozil C. Lovastatin D. Nicotinic acid

Correct Answer: Cholestyramine Bile acid sequestrants tend to raise triglycerides and have only a modest effect on HDL. The rest of the lipid-lowering medications lower triglycerides and raise HDL to varying degrees.

Metabolic syndrome is characterized by all of the following except: A. Abdominal obesity B. Fasting glucose greater than 100 mg/dL C. Increased lipoprotein(a) [Lp(a)] D. Small, dense LDL particles

Correct Answer: Increased lipoprotein(a) [Lp(a)] To make a diagnosis of metabolic syndrome, the patient must have three or more of the following five factors: abdominal obesity, low HDL, elevated triglycerides, elevated blood pressure, or elevated fasting glucose. Small, dense LDL particles are part of the syndrome, but their measurement is not required for diagnosis. Increased Lp(a) is a risk factor for coronary heart disease, but it is not part of metabolic syndrome.

The pattern of atherogenic dyslipidemia is frequently encountered in patients with diabetes and metabolic syndrome. Which is not true of this dyslipidemia?

A. Patients often have rapid progression to coronary heart disease (CHD) B. Statins effectively reduce the preponderance of small, dense LDL particles C. Patients often have marked elevation in LDL D. Hemostatic function is prothrombogenic

Correct Answer: Patients often have marked elevation in LDL Patients with the atherogenic profile have normal or modest increases in LDL. The total number of particles is increased, however, with a B-type pattern (small, dense, highly atherogenic). Statins reduce these LDL particles, as well as modestly raising HDL and lowering triglycerides. These patients often have impaired fibrinolysis and endothelial dysfunction, leading to a prothrombogenic state. The end result is an accelerated progression to CHD.

A 48-year-old male patient is found to have an HDL of 38 mg/dL. Which of the following is not true? A. Exercise can be beneficial in raising HDL B. HDL less than 40 mg/dL is a powerful predictor of cardiac risk C. Smoking tends not to affect HDL levels as much as other lipid parameters D. Nicotinic acid raises HDL more effectively than statins

Correct Answer: Smoking tends not to affect HDL levels as much as other lipid parameters Low HDL (<40 mg/dL) is a powerful predictor of cardiac risk. Options to raise HDL include exercise and pharmacotherapy with nicotinic acid. Smoking has a detrimental effect on all lipid parameters, including HDL.

A 60-year-old man with hypertension and continued tobacco use visits your office for a physical. Initial labs reveal a total cholesterol of 340 mg/dL, LDL of 210 mg/dL, and HDL of 35 mg/dL. What would you recommend to lower his cholesterol? A. Start diet therapy B. Start diet therapy and an exercise program C. Start diet therapy, an exercise program, and a statin D. Repeat the labs to confirm the cholesterol measurement and then start diet therapy E. Repeat the labs to confirm the cholesterol measurement and then start medication

Correct Answer: Start diet therapy, an exercise program, and a statin This man is at extremely high risk of coronary heart disease, given his numerous risk factors: male, age over 45 years, hypertension, and active smoking. Compounding these factors is the markedly elevated LDL level. The most aggressive therapy, including diet, exercise, and medication (statins as first-line pharmacotherapy), should be pursued without delay. There is no reason to repeat the measurement.

A 35-year-old man comes to your office for a physical prior to running a marathon. He feels well except for some occasional numbness on the plantar surface of his feet. On physical examination, you note an unusual orange hue to his tonsils. Routine lab work is notable for a low HDL of 10 mg/dL but normal triglycerides and LDL. What is his most likely diagnosis? A. Lecithin-cholesterol acetyltransferase (LCAT) deficiency B. Familial dysbetalipoproteinemia C. Fish-eye disease D. Tangier disease

The clinical findings of orange tonsils and extremely low HDL suggest the diagnosis of Tangier disease, an inherited disease associated with increased HDL catabolism. His foot numbness may be an early manifestation of peripheral neuropathy that can also be seen with Tangier disease. LCAT deficiency is also associated with low HDL, but orange tonsils are not characteristic. Fish-eye disease is a mild form of LCAT deficiency. Familial dysbetalipoproteinemia is associated with increased very-lowdensity lipoproteins (triglycerides).

A 48-year-old woman presents for a follow-up visit for hypertension. Her blood pressure is still 145/90 mm Hg despite adherence to diuretic therapy. From her last physical, you notice that she has significant abdominal obesity (waist circumference of 37 inches) and evidence of insulin resistance (fasting glucose of 138 mg/dL). Her triglyceride level was 300 mg/dL. Which of the following would you expect? A. Large LDL particles B. An elevated serum aldosterone level C. An elevated serum estrogen level D. An HDL less than 50 mg/dL E. A normal C-reactive protein level

Correct Answer: An HDL less than 50 mg/dL This patient most likely has metabolic syndrome, as evidenced by her abdominal obesity, hypertension, insulin resistance, and elevated triglyceride levels. She meets criteria for diagnosis. A low HDL (<50 mg/dL in women and <40 mg/dL in men) is also often associated with this disorder. LDL particles are usually small rather than large. Patients also may have elevated proinflammatory markers, such as C-reactive protein. Elevated aldosterone and estrogen levels are not characteristics of metabolic syndrome.

A 36-year-old woman visits you for an employment physical. She has not seen a physician in years, but feels well. She has no cardiac risk factors. Her initial fasting lipid profile reveals a total cholesterol of 240 mg/dL, HDL of 50 mg/dL, LDL of 90 mg/dL, and triglycerides (TG) of 400 mg/dL. In managing her lipid abnormalities, all of the following would be important to do except A.

Correct Answer: Ask her about use of the progestin-only mini-pill This patient has an isolated hypertriglyceridemia but an otherwise normal lipid profile. She could certainly have a familial or idiopathic lipid disorder. However, other diseases, including alcoholism, diabetes, obesity, hypothyroidism, and chronic renal insufficiency, can be associated with high TG. Answers A, B, and C attempt to rule out these other causes. Medications, such as estrogens (found in combined oral contraceptives), high-dose diuretics, and nonselective -blockers, can also be associated with high TG. Progestin (the main component of the mini-pill) is more associated with low HDL rather than high TG.

A 63-year-old asymptomatic woman with type 2 diabetes and who follows a heart-healthy diet and exercise program has a blood pressure of 122/76 mm Hg, hemoglobin A1c of 6.6%, normal thyroidstimulating hormone, normal transaminases, a total cholesterol of 212 mg/dL, triglycerides of 140 mg/dL, an HDL of 42 mg/dL, and an LDL of 112 mg/dL. She has no history of cardiovascular disease and is on the following stable doses of medications: lisinopril 40 mg once daily, aspirin 81 mg once daily, and atorvastatin 10 mg once daily. Which of the following is the most appropriate course of treatment? A. Coronary angiography B. Start ezetimibe C. Increase atorvastatin dose D. Continue current management

Correct Answer: Increase atorvastatin dose The goal for LDL cholesterol is less than 100 mg/dL in all patients with known coronary heart disease or "coronary heart disease equivalents," such as diabetes. Therefore, Answer D is incorrect as this patient's LDL is not at goal. Unlike ezetimibe (Answer B), statins are first line for reducing LDL cholesterol because of their proven efficacy in reducing cardiovascular events. Coronary angiography is not indicated in asymptomatic patients.

An 87-year-old petite, diabetic woman is brought to the emergency room by her family for lethargy, delirium, and tea-colored urine for the last 24 hours. On exam, she is confused, is afebrile, and has a pulse of 112 beats/min, blood pressure of 98/52 mm Hg, respirations of 22 breaths/min, and oxygen saturation of 96% on room air. Urine dipstick is hemoglobin positive with no red blood cells identified on microscopy. Her medications include glimepiride 4 mg daily, aspirin 81 mg daily, lisinopril 40 mg daily, simvastatin 80 mg daily, and gemfibrozil 600 mg twice daily. Which of the following is most likely responsible for this clinical presentation? A. Dementia B. Simvastatin and gemfibrozil C. Simvastatin D. Glimepiride

Correct Answer: Simvastatin and gemfibrozil This patient is suffering from rhabdomyolysis-induced renal failure. The tea-colored, hemoglobin-positive urine in the absence of red blood cells is caused by myoglobin from muscle breakdown. Risk factors for drug-induced rhabdomyolysis in this patient include small size, female gender, and advanced age. Gemfibrozil increases the risk of statin-induced rhabdomyolysis by fivefold. Dementia does not cause acute illness and, while glimepiride may cause hypoglycemia, which may present as lethargy and delirium, it does not explain the urine findings.

A 63-year-old male with type 2 diabetes presents to your office 6 months after suffering a myocardial infarction. Since the time of his heart attack, he has been following a diabetic hearthealthy diet as instructed by the hospital nutritionist. He participates in 30 minutes of aerobic

exercise daily and takes the following medications: insulin 70/30, metoprolol 50 mg twice daily, lisinopril 40 mg once daily, aspirin 81 mg once daily, omeprazole 40 mg once daily, clopidogrel 75 mg once daily, and fluvastatin 40 mg once daily. The patient's hemoglobin A1c (HgbA1c) is 6.4%. He is sent to you for evaluation and treatment of his cholesterol: total cholesterol 177 mg/dL, triglycerides 336 mg/dL, HDL 42 mg/dL, LDL 68 mg/dL. Which of the following is the most appropriate recommendation? A. Increase his insulin B. Continue current treatment and check lipids in 3 months to give dietary changes more time to work C. Start omega-3 acid ethyl esters (4 g qd) or fibrate therapy D. Start colesevelam 1875 mg twice daily

Correct Answer: Start omega-3 acid ethyl esters (4 g qd) or fibrate therapy The patient is at his LDL goal of less than 100 mg/dL (optional goal of <70 mg/dL) but has triglycerides over 200 mg/dL and therefore has a secondary target for non-HDL cholesterol (total cholesterol HDL) of less than 130 mg/dL (optional goal of <100 mg/dL). His current non-HDL is 135 mg/dL. Although triglycerides are inversely related to glucose control and good glycemic control is a first-line treatment for hypertriglyceridemia, this patient already has good glucose control as demonstrated by his HgbA1c of 6.4%. The patient has been following a heart-healthy diet for the last 6 months, and this is an adequate amount of time to realize the benefits of dietary changes. Waiting longer is not likely to have further impact. Bile acid sequestrants such as colesevelam tend to increase triglycerides, and are therefore not appropriate treatment for a patient with hypertriglyceridemia. Both high-dose omega-3 acid ethyl esters (4 g daily) and fibrate therapy are effective modalities for reducing triglycerides, resulting in a reduction in non-HDL cholesterol.