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Is Atherosclerosis in Diabetes and Impaired Fasting Glucose Driven by Elevated LDL Cholesterol or by Decreased HDL Cholesterol?

Response to Schulze and Hoffmann

¹ Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria
² Department of Medicine, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
³ Institute for Clinical Chemistry, Feldkirch, Austria

Address correspondence to Heinz Drexel, MD, Professor of Medicine, VIVIT, Carinagasse 47, A-6800 Feldkirch, Austria. E-mail: vivit{at}lkhf.at

Our study (1) demonstrates that an LDL-related lipid factor in coronary patients with type 2 diabetes is 1) not elevated, 2) not associated with significant coronary stenoses, and 3) not significantly predictive for future events. Whereas the first two findings did not even show a trend for the LDL-related factor, our prospective data need to be confirmed by a longer follow-up with more end points. We have amply discussed this in our report, and Schulze and Hoffmann (2) also raise this point.

Since currently 58% of coronary patients are on statins (3) and lipid-lowering medication very frequently is required in diabetes to achieve the stringent LDL cholesterol goals that have been put forth for this "CAD risk equivalent," exclusion of diabetic patients on lipid-lowering therapy in our investigation would have excluded diabetic coronary patients receiving up-to-date medical care and thus would have rendered the study population utterly unrepresentative of today’s clinical setting.

Factor analysis is the appropriate technique to extract an integral factor representing diabetic dyslipidemia from the individual lipid parameters measured. The power of this factor to predict vascular events can be subsequently evaluated in Cox regression models. This approach is novel in the study of lipid risk factors in patients with diabetes but has been previously applied to investigate the metabolic syndrome (4).

We included apolipoprotein B levels in our factorial analysis. Non-HDL cholesterol represents the total cholesterol carried by VLDL, IDL (intermediate-density lipoprotein), and LDL, of which each particle contains one molecule of apolipoprotein B. Serum levels of apolipoprotein B are thus closely related to non-HDL cholesterol.

Even though cardiovascular risk is significantly reduced in diabetic patients by statins, it remains at a very high level in these patients (5). The consistent association of the HDL-related factor with glycemia, with significant stenoses and with the future incidence of vascular events, provides compelling and conclusive evidence that the main lipid risk factor in our patients with diabetes is the triad of low HDL cholesterol, small LDL particles, and high triglycerides.

References

1. Drexel H, Aczel S, Marte T, Benzer W, Langer P, Moll W, Saely CH: Is atherosclerosis in diabetes and impaired fasting glucose driven by elevated LDL cholesterol or by decreased HDL cholesterol? Diabetes Care 28:101–107, 2005
   
2. Schulze MB, Hoffmann K: Is atherosclerosis in diabetes and impaired fasting glucose driven by elevated LDL cholesterol or by decreased HDL cholesterol? (Letter). Diabetes Care 28:1264, 2005
   
3. Clinical reality of coronary prevention guidelines: a comparison of EUROASPIRE I and II in nine countries: EUROASPIRE I and II Group: European Action on Secondary Prevention by Intervention to Reduce Events. Lancet 357:995–1001, 2001
   
4. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT: The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288:2709–2716, 2002
   
5. Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH: Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 364:685–696, 2004
   

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This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Drexel, H. Articles by Saely, C. H. Search for Related Content PubMed Articles by Drexel, H. Articles by Saely, C. H. Social Bookmarking                What's this?