|Posted by ralph on December 22, 2009 at 3:15 PM|
Hannover, Germany - A small study published this week hints that the effects of HDL cholesterol differ in healthy patients from those with diabetes mellitus . HDL cholesterol in individuals with diabetes has impaired endothelial protective functions compared with the HDL from healthy subjects, although treatment with extended-release niacin can improve these endothelial protective effects, according to researchers.
Publishing their findings online December 21, 2009 in Circulation, lead investigator Dr Sajoscha Sorrentino (Hannover Medical School, Germany) and colleagues write that because recent HDL-raising intervention studies have yielded mixed results, "circulating HDL-cholesterol levels alone likely do not represent an adequate measure of therapeutic efficacy, and indexes of HDL functionality are urgently needed for assessment of the potential of HDL-targeted therapies to exert vasoprotective effects."
Speaking with heartwire, senior investigator Dr Ulf Landmesser (University of Zürich, Switzerland), said the results have implications for clinical research.
"We have to understand that we can't look only at the HDL levels in the plasma, but we need to look at the quality," he said. "The quality of the HDL is not the same in different patients. This is very important for targeting HDL as a treatment. Second, niacin therapy is a promising way not only to raise HDL but also to improve the quality; it is a good treatment option, especially if the larger outcomes data are positive."
Role of nitric oxide with HDL
To heartwire, Landmesser said that researchers are still learning about the protective effects of HDL. While reverse cholesterol transport, removing cholesterol from the plaque and bringing it to the liver, leading to a regression of atherosclerosis, is one mechanism, research suggests that HDL's direct effects on nitric-oxide (NO) production are also important.
For example, previous studies have shown that HDL cholesterol has endothelial protective effects, such as stimulating NO production and endothelial-dependent vasomotion. In addition, some studies suggest that HDL has antioxidant effects, while others have shown that it promotes endothelial-progenitor-cell (EPC)-mediated endothelial repair. Most of these studies, however, were performed using HDL isolated from healthy subjects or reconstituted HDL.
In this study, the researchers isolated HDL cholesterol from 10 healthy subjects and 33 individuals with diabetes and low HDL-cholesterol levels and measured the effects of HDL on endothelium-dependent vasodilation and EPC-mediated endothelial repair.
Compared with healthy subjects, the endothelial protective properties of HDL from diabetic patients were markedly impaired. Whereas the HDL from healthy subjects stimulated endothelial NO production, reduced endothelial oxidant stress, improved endothelium-dependent vasodilation, and improved early EPC-mediated endothelial repair, these benefits were not observed in patients with diabetes.
"Basically, there have been six or seven studies looking at how HDL stimulates endothelial function, in particular nitric-oxide production in the endothelium," said Landmesser. "This is the first study, to my knowledge, that shows that while this is true for HDL in healthy subjects, it is not the case in subjects with diabetes."
Randomized to niacin treatment
Diabetic patients with low HDL-cholesterol levels, those meeting the criteria for metabolic syndrome, are regularly treated with HDL-raising therapies. For this reason, the researchers wanted to see if niacin altered the quality of their HDL, and they randomized the diabetic patients to extended-release niacin (1500 mg/day) or placebo for three months. Previous studies, said Landmesser, showed that niacin potentially remodels the protein composition of the HDL, making it more vasoprotective.
Treatment with niacin increased HDL-cholesterol levels, but more important, also improved the endothelial protective effects compared with the HDL from healthy subjects. For example, in those diabetic patients treated with niacin, endothelial-cell NO production and EPC-mediated endothelial repair was stimulated. Niacin also reduced the amount of myeloperoxidase-induced oxidant damage to HDL.
"The quality of the HDL was better after niacin," Landmesser told heartwire. "It raises HDL, which has been known for a long time, but the quality of the HDL, the vasoprotective effects, are improved after niacin, and this might actually be more important than simply raising HDL-cholesterol levels."