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Baltimore Lipid Center Towson, Md.
In response to "Raising HDL Cholesterol in Patients With Diabetes" by Dr. Robert H. Eckel (DOC News, August 2007, page 4), I would take issue with the therapeutic goal and with the drug therapy recommended.
The primary cardiovascular goal in diabetic patients, as with any patients, should be the reduction of clinical events, especially hard events, such as nonfatal myocardial infarction and cardiovascular mortality. Raising or lowering various serum lipid levels is fraught with confusion in its correlation with clinical-event reduction, and in some cases, such as with the cholesterol-ester transfer protein (CETP) inhibitor, torcetrapib (Pfizer), with clinical harm.
It is truly our lipoproteins, not our lipids, that determine our cardiovascular fate!1 Insulin-resistant patients swim in a tide of dysfunctional HDL particles and increased numbers of small, dense atherogenic LDL particles and triglyceride-rich remnant particles, which can be readily assessed by the clinician through determining non-HDL-C, Apolipoprotein B (ApoB), or NMR-derived LDL-particle counts.2-5 These atherogenic particles abound in low HDL-C clinical situations, and we have abundant evidence that reduction of these atherogenic ApoB particles with statins reduce hard events. The National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) guidelines recognize this and recommend in low HDL-C situations not niacin therapy to raise HDL-C but reduction of LDL-C as a first priority, and then non-HDL-C (surrogate for ApoB) to goal.6
The statins are currently the most potent upregulators of ApoB receptors in our therapeutic armamentarium (in many cases with assistance from the cholesterol absorption inhibitor ezetimibe), and need to be the cornerstone of treatment in diabetic low HDL-C situations, not niacin.
The fibrates and niacin are used as secondary drugs to further reduce atherogenic particles, and may have additional benefits in improvement of HDL function in insulin-resistant patients, and further reduction of clinical events when used in combination therapy with statins (clinical trials currently under way).7 The goal should be firmly focused on reduction of clinical events in low HDL-C patients, not necessarily on raising the cholesterol content of their HDL particles.8
References
2. Dayspring T, Pokrywka GS: Pharmacotherapeutic decisions in menopausal women with cardiovascular risk. Future Lipidology 2:197–210, 2007.
3. Kathiresan S, Otvos JD, Sullivan LM, et al.: Increased small
low-density lipoprotein particle number: A prominent feature of the metabolic
syndrome in the Framingham Heart Study. Circulation 113: 20–29, 2006.
4. Cromwell WC, Otvos JD: Heterogeneity of low-density lipoprotein particle number in patients with type 2 diabetes mellitus and low-density lipoprotein cholesterol <100 mg/dl. Am J Cardiol 98: 1599–1602, 2006.[Medline]
5. Kontush A, Chapman MJ: Functionally defective high-density
lipoprotein: A new therapeutic target at the crossroads of dyslipidemia,
inflammation, and atherosclerosis. Pharmacol Rev 58: 342–374, 2006.
6. Mosca L, Banka CL, Benjamin EJ, et al.: Evidence-based guidelines
for the prevention of cardiovascular disease in women: 2007 update for the
Expert Panel/Writing Group. J Am Coll Cardiol 49: 1230–1250, 2007.
7. Dayspring T, Pokrywka G: Fibrate therapy in patients with metabolic syndrome and diabetes mellitus. Curr Atheroscler Rep 8: 356–364, 2006.[Medline]
8. Singh IM, Shishehbor MH, Ansell BJ: Raising HDL as a therapeutic
target: A systematic review. JAMA 298: 786–798, 2007.
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