<KOSP - incidence of low HDL>
Here are two recent relevant abstracts. Note the sentence I bolded in the first abstract. The second abstract implies niacin is much more effective than gemfibrozil in raising levels of clinically relevant HDL.
Curr Atheroscler Rep 2001 Sep;3(5):365-72 Related Articles, LinkOut, Books
New developments in the prevention of atherosclerosis in patients with low high-density lipoprotein cholesterol.
Brousseau ME, Schaefer EJ.
Jean Mayer-USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, USA. mbrousseau@hnrc.tufts.edu
Epidemiologic studies have established that a low concentration of plasma high-density lipoprotein (HDL) cholesterol is an independent risk factor for coronary heart disease (CHD). In the United States, a low HDL cholesterol concentration is the most prevalent lipid abnormality observed in men with known CHD. Despite this fact, surprisingly few clinical trials have been designed to investigate the effects of pharmacologic agents on HDL cholesterol-raising and CHD risk in large populations, perhaps due, in part, to the lack of available drugs having significant HDL cholesterol-raising potential. The purpose of this report is to review recent primary and secondary prevention trials that have explored the relationships between drug therapy, HDL cholesterol concentration, and CHD events or progression. Emphasis will be placed on the results of the Veterans Affairs High-Density Lipoprotein Trial, a study that was specifically designed to test the hypothesis that HDL cholesterol-raising with gemfibrozil would reduce CHD morbidity and mortality in patients with CHD whose primary lipid abnormality was a low level of HDL cholesterol.
Arterioscler Thromb Vasc Biol 2001 Nov;21(11):1783-9 Related Articles, Books, LinkOut
Niacin, but Not Gemfibrozil, Selectively Increases LP-AI, a Cardioprotective Subfraction of HDL, in Patients With Low HDL Cholesterol.
Sakai T, Kamanna VS, Kashyap ML.
Cholesterol Research Center, Department of Veterans Affairs Healthcare System, Long Beach, Calif, and the Department of Medicine, University of California, Irvine.
- Evidence indicates that the high density lipoprotein (HDL) subfraction containing apolipoprotein A-I without apolipoprotein AII (LP-AI) is more antiatherogenic than HDL particles containing apolipoprotein A-I and apolipoprotein A-II (LP-AI+AII). This study examined the effect of extended-release niacin (niacin-ER) and gemfibrozil on LP-AI and LP-AI+AII particles in patients with low levels of HDL cholesterol (HDL-C). Mechanisms by which these agents modulate HDL particles were investigated by in vitro studies using human hepatoblastoma (Hep G2) cells. A total of 139 patients with low HDL-C (</=40 mg/dL) were randomized to niacin-ER or gemfibrozil in a multicenter double-blind trial. Patients were dose-escalated with once-nightly niacin-ER (1 to 2 g) or gemfibrozil (1.2 g) for 19 weeks. Niacin-ER had a greater effect in raising HDL-C and apolipoprotein A-I levels than did gemfibrozil. Niacin-ER at 1- and 2-g doses increased LP-AI levels by 8.7+/-4.0% (P=0.033) and 24.0+/-4.4% (P<0.001), respectively. Gemfibrozil had no consistent effect on LP-AI levels. LP-AI+AII levels increased 5% to 8% by both agents. In vitro studies showed that niacin, but not gemfibrozil, selectively decreased the uptake of (125)I-labeled LP-AI holoparticles by Hep G2 cells. The uptake of [(3)H]cholesterol ester was approximately 75% greater from LP-AI versus LP-AI+AII particles, but neither niacin nor gemfibrozil affected cholesterol ester uptake. These data indicate that unlike gemfibrozil, niacin selectively increases LP-AI compared with LP-AI+AII particle concentration in patients with low HDL-C levels. The mechanism of action of increased LP-AI concentration appears to be mediated by decreased hepatic removal of LP-AI particles, which are more efficient in reverse cholesterol transport, thus suggesting an additional mechanism by which niacin mediates its antiatherogenic properties.
Peter |
