Showing papers by "Howard N. Hodis published in 2000"

Preliminary Guidelines for the Evaluation and Management of Dyslipidemia in Adults Infected with Human Immunodeficiency Virus and Receiving Antiretroviral Therapy: Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group

Abstract: Dyslipidemia is a prevalent condition that affects patients infected with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy. These preliminary recommendations summarize the current understanding in this area and propose guidelines for management. Existing guidelines for the management of dyslipidemia in the general population formed the general basis for our recommendations. Data on the prevalence and treatment of dyslipidemia of HIV-infected patients, implications of treatment-related dyslipidemia in other chronically ill populations, and pharmacokinetic profiles for the available hypolipidemic agents in non-HIV populations were considered. Although the implications of dyslipidemia in this population are not fully known, the frequency, type, and magnitude of lipid alterations in HIV-infected people are expected to result in increased cardiovascular morbidity. We propose that these patients undergo evaluation and treatment on the basis of existing guidelines for dyslipidemia, with the caveat that avoidance of interactions with antiretroviral agents is paramount.

Probucol Reduces Oxysterol Formation in Hypertensive Rabbits

Abstract: The role of lipid peroxidation during the pathogenesis of atherosclerosis has been described through numerous studies and has provided compelling evidence for free radical-mediated processes that link hypertension with atherosclerosis. However, there remains only limited information concerning peroxidative processes in hypertension and their modulation by antioxidants. In the present study, the formation of cholesterol oxidation products was used as a measure of in vivo lipid peroxidation after hypertension induced by coarctation of the aorta in New Zealand White rabbits. The rabbits were fed a standard chow diet devoid of cholesterol or cholesterol oxidation products such that the measured cholesterol oxides in the plasma and aortic tissues would most plausibly arise from endogenous oxidation of cholesterol. After 12 weeks of hypertension, all of the measured cholesterol oxides increased significantly over baseline levels in the surgically coarctated animals; however, this increase was significantly less in hypertensive probucol-treated animals. Similarly, the cholesterol oxide content of aortic tissue from the surgically coarctated animals was significantly greater than that found in normotensive control aortas, and probucol treatment significantly reduced the increase in cholesterol oxide content of aortic tissue relative to that of hypertensive animals not receiving the antioxidant. These findings in hypertensive animals suggest that cholesterol oxidation products measured in plasma and aortic tissue can be derived from endogenous free radical activity and that this activity is enhanced under specific pathological conditions.

Myocardial Ischemia and Lipoprotein Lipase Activity

Abstract: It has been >55 years since Hahn1 first observed that the intravenous injection of heparin abolished postprandial lipemia in dogs; subsequently, Korn and Quigley2 identified the factor released by intravenous heparin as a triglyceride lipase. Since that time, the putative role of lipoprotein lipase in atherosclerosis has expanded tremendously. Lipoprotein lipase is a key enzyme in the regulation of lipid fuel disposal,3 and it provides fatty acids for tissue utilization by catalyzing the hydrolysis of triacylglycerol circulating in triglyceride-rich lipoproteins. Anchored to the surface of the capillary endothelium by glycosaminoglycans, lipoprotein lipase hydrolyzes plasma chylomicrons and VLDL to remnant particles. As such, lipoprotein lipase is the rate-limiting enzyme responsible for the removal of plasma triglyceride-rich lipoproteins from the circulation. Although expressed in most tissues of the body, in particular, skeletal and heart muscle and adipose tissue, lipoprotein lipase is also expressed and secreted by macrophages. Lipoprotein lipase is important for the transfer of phospholipids and apolipoproteins to HDL and, thus, is critical for the formation of this particle.4 Apolipoprotein C-II is an essential cofactor for the activation of lipoprotein lipase activity, …

Efficacy of two lipid-lowering treatments on quantitative coronary angiographic endpoints.

Abstract: This study contrasts the sensitivity of four quantitative coronary angiography (QCA) measures (percent diameter stenosis [%S], minimum lumen diameter, average segment diameter, and percent involvement) in detecting 2-year treatment effects of two lipid-lowering therapies and reports on the longitudinal pattern after 4 years of treatment on the primary QCA trial endpoint (%S) for all, mild/moderate (<50%S), and severe lesions (≥50%S). Patient cohorts were followed up from two randomized, placebo-controlled clinical trials of lipid-lowering therapies—colestipol/niacin in the Cholesterol Lowering Atherosclerosis Study (CLAS) and lovastatin in the Monitored Atherosclerosis Regression Study (MARS). Identical QCA methodology was used. In CLAS, the largest 2-year treatment effect size (=0.60) was noted for %S. In MARS, equivalent 2-year effect sizes (=0.15) were noted for three QCA measures. The largest 2-year effect size in %S was found in CLAS for mild/moderate lesions (=0.55) and in MARS for severe lesions (=0.31). Treatment in CLAS led to regression of disease in the first 2 years; treatment in MARS slowed progression of disease in the first 2 years and led to regression of disease after 4 years. Colestipol/niacin reduced progression of mild/moderate and severe lesions over the first 2 years of therapy; lovastatin reduced the progression of severe lesions over the last 2 years of therapy. We conclude that reducing the progression of atherosclerosis is not a simple proposition; maximal therapy for reducing and stabilizing atherosclerosis most likely will result from the selection of agents targeted at specific lesions.