Tip of the Day

 Case Study 1: Mild Hypertriglyceridemia in a South Asian Patient With Type 2 Diabetes
A 31-year-old South Asian man presents for a coronary heart disease (CHD) risk assessment. He is 5'10", weighs 181 pounds, has a waist circumference of 36", and a blood pressure of 135/85 mm Hg. He has had type 2 diabetes for 3 years. He takes 1000 mg of metformin and 40 mg of atorvastatin once daily. His mother had coronary artery bypass graft surgery with complications at age 53.

 

 Lipid panel: total cholesterol: 207 mg/dL; high-density lipoprotein cholesterol: 30 mg/dL; low-density lipoprotein cholesterol: 107 mg/dL; and triglycerides: 350 mg/dL. Blood glucose level: 130 mg/dL. Other laboratory values: creatinine: 1 mg/dL; creatinine clearance: 103.1 mL/min; blood urea nitrogen: 14 mg/dL; and uric acid: 9.1 mg/dL.

Dr. Davidson: This patient has all the criteria for a metabolic syndrome: waist circumference of 36" (for Asian man); elevation in triglycerides; low HDL cholesterol level; systolic blood pressure >130 mm Hg, fasting glucose of 100 mg/dL.

Dr. Miller: In addition to lifestyle changes, fenofibrates and omega-3 fatty acids should now be considered beyond statin therapy to lower his elevated triglyceride levels. Equally important is better control of his glucose, because without improvement in this metabolic parameter, it is highly unlikely that triglyceride levels will normalize.

Dr. Ballantyne: His lipid levels are not adequate despite being on 40 mg of atorvastatin, which indicates a severe, probably hereditary, dyslipidemia that may be familial combined hyperlipidemia. Knowing his baseline LDL cholesterol level, his mother's lipid profile, and his lipoprotein (a) level would be helpful. I would target LDL cholesterol <100 mg/dL. A carotid ultrasound can measure his intima-media thickness. If he has atherosclerosis, then I may use three therapies, adding any of those mentioned in addition to a statin, and maybe even change his statin.

Dr. Bays: I would look at fish oils as revealing the true atherogenicity of this person's dyslipidemia. Omega-3 fatty acids, like fibrates, convert VLDL particles to LDL particles, and if I treat a patient with a triglyceride level of 350 mg/dL with omega-3 fatty acids, the LDL cholesterol level will often increase. I would treat this patient with omega-3 fatty acids, leave him on atorvastatin and perhaps add ezetimibe.

Dr. Harris: His LDL cholesterol may not increase if you put him on fish oil because he is on atorvastatin already. If he were on monotherapy with omega-3 fatty acids and his triglycerides were higher, the LDL cholesterol level may rise.

Dr. Davidson: I would use fenofibrate because it lowers uric acid levels. Adding niacin instead may make controlling his glucose difficult. Ultimately, we realize that unless he reduces his caloric intake and loses weight, we will probably use multiple drugs.

Case Study 2: Severe Hypertriglyceridemia in a Patient With Type 2 Diabetes
A 36-year-old woman is referred to the lipid clinic by a dermatologist. She was diagnosed with type 2 diabetes 3 years ago, has a history of pancreatitis, a sedentary lifestyle, has smoked 1 pack per day for 10 years, and denies the use of alcohol or illicit drugs. Her mother and father are alive and well.

Physical examination shows eruptive xanthomas, and the dermatologist's biopsy revealed triglycerides in the skin lesions.

Blood pressure: 133/89 mm Hg; heart rate: 91 bpm; height: 5'5"; weight: 235 pounds; waist circumference: 41"; body mass index: 30.9 UNITS. Laboratory results: total cholesterol: 300 mg/dL; HDL cholesterol: 20 mg/dL; LDL cholesterol: not calculated; triglycerides: 900 mg/dL; blood glucose: 115 mg/dL. Other laboratory values: creatinine, 1.6 mg/dL; blood urea nitrogen (BUN), 13 mg/dL; uric acid, 3.2 mg/dL; Hgb A1C level: 7.3%.

Dr. Davidson: Cigarette smoking does not cause hypertriglyceridemia. Low HDL cholesterol and inactivity do.

Dr. Miller: The patient has a primary hypertriglyceridemia. I would confirm that some of the exogenous causes, such as alcohol, are withdrawn. Estrogen-related therapies also trigger high triglycerides. We have had success using omega-3 fatty acids and fibrates. In concert with weight loss and exercise, we have had success with omega-3 fatty acids in lowering triglycerides in patients with baseline values as high as 8000 mg/dL. However, I am unaware of any studies that have evaluated either omega-3 fatty acids or fibrates prospectively for the prevention of recurrent pancreatitis. Omega-3 fatty acids possess anti-inflammatory properties that may be clinically useful in patients with systemic inflammatory processes.

Dr. Bays: The issue is the patient's prior bout of pancreatitis. The first priority should be to lower the triglycerides to <500 mg/dL. I would start with diet and lifestyle changes. It is extraordinary how effective weight reduction and a diet low in simple carbohydrates are in lowering triglycerides in patients. She does not admit to alcohol use. The effects of alcohol are complicated. Although it can cause fatty liver and increase triglycerides, chronic low alcohol consumption can reduce triglycerides by improving glucose sensitivity. In studies in which Dr. Ballantyne was a co-author, intermittent alcohol intake increased triglyceride levels in individuals without hypertriglyceridemia but had little effect on those who already had hypertriglyceridemia. A diet with a low glycemic index is important. We provide patients with a handout that lists glycemically acceptable and glycemically unacceptable diets. We eliminate fruit juices and sugared soda from the diets of patients with hypertriglyceridemia. Once we remove these and add omega-3 fatty acids, we may try to lower triglycerides to <500 mg/dL, and then focus on the atherogenicity that remains with triglycerides at this level.

Dr. Ballantyne: One could use niacin in this case but cautiously up-titrate it due to the blood glucose of 115 mg/dL. The creatinine level of 1.6 is a concern if we use fenofibrate. It may increase but it may be a lab error because the BUN was normal. I would perform a urinalysis to rule out nephrotic syndrome. One of the issues with alcohol is an interaction with dietary fat. A high fat load plus alcohol can increase her triglycerides to as high as 2000 mg/dL or 3000 mg/dL in the postprandial state. In addition, a meal of fried foods can induce another episode of pancreatitis. Her fat intake must be reduced. She should eat lean cuts of meat and avoid sugars. Exercise, weight loss, and dietary changes can reduce triglyceride levels to between 200 mg/dL and 300 mg/dL.

The HDL cholesterol of 20 mg/dL is also worrisome but could be a laboratory error due to the high triglyceride level.

Dr. Davidson: Does assessing triglycerides in the nonfasting state have value as a predictor of vascular events?

Dr. Miller: The fasting triglyceride level correlates with the postprandial level. Typically, the postprandial triglyceride peak levels occur 4 hours after a fatty meal. However, because fat content and composition is highly variable it is difficult to accurately predict the expected postprandial triglyceride response, although >50% is a reasonable estimate. Therefore, a fasting triglyceride level of 150 mg/dL is likely to increase well beyond 200 mg/dL during the day, depending on the dietary fat consumed. As a result, a "non-fasting" triglyceride level > 200 mg/dL should be followed up with the more traditional and standardized fasting level to determine whether and to what extent lifestyle and other measures may need to be instituted.

Case Study 3: Mixed Dyslipidemia and Subclinical Atherosclerosis

A 54-year-old white man reports to the lipid clinic for a comprehensive evaluation and primary prevention. He is a nonsmoker, exercises regularly, has a low-fat and low-carbohydrate diet, and denies alcohol and illicit drug use. He is currently taking simvastatin 20 mg and aspirin 81 mg daily. The patient's father died from a myocardial infarction at age 49. His sister, age 50, recently underwent percutaneous transluminal coronary angioplasty with stent placement in the left anterior descending and right coronary arteries. His mother has type 2 diabetes and is 75 years old.

The patient is 5'11", weights 190 pounds, has a waist circumference of 38 inches, and a body mass index of 26.5. His blood pressure is 134/82 mm Hg, and his heart rate is 72 bpm. Lipid panel results are: total cholesterol: 170 mg/dL; HDL cholesterol: 30 mg/dL; LDL cholesterol: 90 mg/dL; triglycerides: 250 mg/dL; and non-HDL cholesterol: 140 mg/dL. His LDL particle number is elevated at 1407 nmol/L with the desirable number being less than 1000 nmol/L, and his apoB is also elevated at 130 mg/dL.

Additional laboratory tests revealed a 2-hour postprandial glucose of 210 mg/dL and a hemoglobin A1c of 6.3. His liver enzymes were elevated with an alanine transaminase of 65 U/L, aspartate transaminase of 80 U/L, and a GGT of 145 U/L. Kidney function tests revealed an impaired creatinine clearance of 1.5 mg/dL, elevated blood urea nitrogen of 28 mg/dL, and elevated uric acid of 9.1 mg/dL.

Computed tomography angiography showed significant coronary calcium as well as soft plaque in his left anterior descending artery and calcium in his other arteries.

How would you treat this patient?

Increase the dose of simvastatin to 40 mg /day.
Add 4 g prescription omega-3 fatty acids to 20 mg/day simvastatin.
Add 145 mg fenofibrate to 20 mg/day simvastatin.
Add 1000 mg niacin ER to 20 mg/day simvastatin.
Maintain current treatment of 20 mg/day simvastatin.
Dr. Miller: I would use omega-3 fatty acids but would probably also consider niacin therapy given his tendency to a low HDL cholesterol and elevation of triglycerides. Combination would be effective on top of his statin.

Dr. Davidson: Would you have considered metformin for this patient?

Dr. Miller: I would be more cautious in view of the reduced creatinine clearance.

Dr. Davidson: Would you use pioglitazone? Would anybody use anything for his diabetes?

Dr. Harris: He fit the combination pattern well, so it is not unreasonable to use the omega-3s.

Dr. Bays: I would consider using niacin in this patient. I would be a little concerned about the glucose level because it is borderline high, but given that he has evidence of atherosclerosis, niacin will be effective in improving triglycerides and raising HDL cholesterol. Because patients like this end up being on so many medications, I look at it from a strategic standpoint: what is the easiest way to get them from their baseline to target lipid levels? With niacin, you may reduce the triglycerides to < 200 mg/dL, and you can increase the HDL cholesterol to as high as 35 mg/dL. Then I would focus on further lowering the LDL cholesterol level. One could make the case that he should be switched to the combination of ezetimibe plus simvastatin to drive the LDL cholesterol level down.

Dr. Davidson: Would you catheterize him?

Dr. Ballantyne: No, I would perform a stress test. I do not catheterize based on coronary calcium score. If you see lesions on the angiogram, jump in and start to do something, you can get in trouble. I agree that omega-3 fatty acids are fine but he needs more LDL cholesterol lowering. I am not happy about his LDL cholesterol being 90 mg/dL, and his apoB and LDL particle concentration is high. I would put him on a more effective statin instead of doubling the dose of simvastatin to 40 mg. I would go to atorvastatin, 40 mg/day, or rosuvastatin, or use ezetimibe plus simvastatin.

Comment From Audience: Do you routinely treat chylomicron and check the level?

Comment From Audience: There are no commercial assays currently available in the United States for chylomicron remnants. So we do not measure them, but there are some assays being tested.

Comment From Audience: In the Honolulu Heart Study there was a good correlation between chylomicron remnants and triglyceride levels.

Comment From Audience: This man has systolic hypertension that needs to be treated.

Dr. Davidson: Yes, I think we all agree that this patient must be aggressively treated and that triglyceride lowering is a component of the overall global risk modification.