I would like to comment on treatment of dyslipidemia in the diabetic patient with total cholesterol 195 mg/dL, HDL 32 mg/dL, LDL 98 mg/dL, and triglycerides 195 mg/dL (Item 120-8). According to my calculations, the patient’s LDL should be 124. It’s important to know, however, whether the HDL was measured by the older indirect method or the newer direct method. The direct method gives an HDL value about 10 mg/dL higher than the indirect method—at least in our hospital lab. Since all the original atherosclerotic disease regression trials used the indirect method, our goals for HDL must be based on it. And, since LDL is calculated, a 10 mg/dL “free rise” in HDL means a 10 mg/dL “free drop” in LDL.

If the patient’s stated HDL (32) is a direct measure, his indirect HDL is lower and his calculated indirect LDL is 134, putting him at high risk for an acute atherothrombotic event despite atorvastatin (Lipitor) therapy. If the stated HDL is an indirect measure, then the risk is much less, but still significant—especially in an older patient. 

Try switching statins to rosuvastatin (Crestor) 20 mg daily, as this will raise the HDL and further lower the LDL. If the patient’s LDL is based on an indirect HDL, this should be sufficient. However, if the patient’s LDL is based on a direct HDL, more needs to be done. I would also add ezetimibe (Zetia) 10 mg daily (despite the Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery [ENHANCE] study). This should lower LDL and raise HDL enough to stabilize/regress any extant arterial wall plaque (based on results from A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound Derived Coronary Atheroma Burden [ASTEROID]). Once the LDL-HDL balance is optimized, then in the absence of cigarette smoking, the triglycerides can be ignored unless they rise further.

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Dr. Ruser’s suggestion of niacin or fibrate therapy is an alternative approach. However, even extended-release niacin causes flushing and itching. The fibrate must be fenofibrate (Tricor), as the risk of rhabdomyolysis is too great otherwise. I would add a combination of low-dose fish oil (three capsules daily) and low-dose aspirin (81 mg daily) for its antiplatelet effects to try to prevent intra-arterial thrombosis.

Smokers must quit immediately. Cigarette-smoking diabetics are the youngest to die in my practice.
—William E. Feeman Jr, MD, Bowling Green, Ohio

While Dr. Feeman’s comments regarding indirect vs. direct lipid values are astute, the aggregate of lipid-lowering therapy trials indicates that “thresholds” for LDL may be artificial, i.e., the lower, the better (Lancet. 2005;366:1267-1278). Thus you could argue to push the LDL lower anyway. The difference, as Dr. Feeman implies, might lie primarily in how aggressive you and your patient choose to be.

I do have some mild concerns surrounding the recommendation of Zetia given recent evidence presented in ENHANCE with regard to lack of clinical effectiveness despite numeric lowering of LDL. The data are limited to one trial, however, and most experts have simply urged caution.

Before turning to Crestor, readers should consider that one can get nearly the same additional LDL lowering, HDL rise, and triglyceride lowering by maximizing this patient’s Lipitor dose. (The earlier letter indicated that the patient is already taking seven medications.)

The original question was whether or not medication should be added specifically to improve the patient’s triglyceride or HDL levels. I stand by my original recommendation to consider fish, fish oil, fibrates, and nicotinic acid or an increase in the patient’s Lipitor dose. As always, medication adjustments should be accompanied by exercise and dietary counseling.
—Christopher Ruser, MD (121-16)