Showing papers by "Howard N. Hodis published in 1997"

The Role of Triglyceride-Rich Lipoprotein Families in the Progression of Atherosclerotic Lesions as Determined by Sequential Coronary Angiography From a Controlled Clinical Trial

Abstract: We have demonstrated previously in a subset of Monitored Atherosclerosis Regression Study (MARS) subjects with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease that lovastatin significantly reduces cholesterol-rich lipoprotein B (LpB) but has little effect on complex, triglyceride-rich apolipoprotein (apo) B–containing LpBc (the sum of LpB:C, LpB:C:E and LpA-II:B:C:D:E) particles defined by their apolipoprotein composition. This differential effect of lovastatin on apoB-containing lipoprotein families offered the opportunity to determine in the same subset of MARS subjects the independent relationship of LpB and LpBc with the progression of coronary artery disease. Subjects randomized to either lovastatin (40 mg twice daily) or matching placebo were evaluated by coronary angiography before randomization and after 2 years of treatment, and the overall coronary status was judged by a coronary global change score. In the lovastatin-treated group, there were 22 nonprogre...

Intermediate-Density Lipoproteins and Progression of Carotid Arterial Wall Intima-Media Thickness

Abstract: Background Although LDL cholesterol (LDL-C) is generally accepted to be a major risk factor for progression of atherosclerosis, the traditional measurement of LDL-C includes measurement of IDL. Little is known about the relationship between IDL and progression of atherosclerosis. Therefore, we investigated the association of plasma lipoprotein subclasses with progression of preintrusive carotid artery atherosclerosis in the Monitored Atherosclerosis Regression Study (MARS). Methods and Results MARS was a randomized, double-blind, placebo-controlled serial arterial imaging trial conducted in subjects 37 to 67 years old with angiographically defined coronary artery disease. Analytical ultracentrifugation was used to determine lipoprotein subclasses, including LDL (Sf 0 to 12), IDL (Sf 12 to 20), VLDL (Sf 20 to 400), and HDL (F1.20 0 to 9) in 188 subjects. Subjects were randomized to a cholesterol-lowering diet plus placebo or lovastatin 80 mg/d. The outcome measure, the annual progression rate of the distal...

Antioxidants and atherosclerosis: an overview.

Abstract: There is substantial evidence that the early stages of atherosclerosis are comprised of a series of oxidative processes that accompany the known risk factors attributed to abnormal plasma lipid profiles. The current opinion in this field holds that hyperlipidemia along with enhanced oxidation of lipoprotein lipids are separate but interacting factors giving rise to the formation of atherogenic lesions [23]. Evidence in support of the lipid hypothesis is substantial, shown in recent years by the dramatic reduction in coronary artery disease arising from lipid lowering therapies ‐ particularly cholesterollowering drugs. However, progression of atherosclerosis even with aggressive lipid-lowering therapies indicates that other factors are involved in a substantial segment of the population. There are certainly genetic factors that determine predisposition to disease based on abnormalities in lipid metabolism and deposition, however, other genetically determined as well as genetically independent processes appear to be of importance. These include the formation and elimination of oxidants and their effects on vascular tissues, as these oxidants can be derived either via metabolic processes or by external sources. The oxidant-mediated processes thought to be of importance in early atherogenesis are described in Table 1. These steps apply to the oxidation of serum lipoproteins as well as to vascular tissues, and interaction of lipoproteins with vascular cells through oxidative events appears to be central to the formation of atherosclerotic lesions. Each of these events are characteristic of the generally accepted processes involved in atherosclerosis. Oxidants have been shown to produce atherogenic responses independent of lipid levels and the mechanisms of injury include many of the biological events described for atherogenesis. Injury can be manifested by acute damage to cell components and vascular cell death, however, this is less likely than the non-lethal injury that is produced by oxidized LDL or by the inflammatory response encountered in vivo which causes perturbations in cell function. Support for the role of oxidants in the development of atherosclerosis also comes from recent clinical trials demonstrating antioxidant protection beyond that afforded by lipid lowering therapies [13,19]. The therapeutic potential of antioxidants can be demonstrated in many of the key steps described for early atherosclerosis. The steps of interest include: 1) Injury to the vessel wall, lipoprotein-derived oxidants have been shown to damage the endothelium through direct reactions with membranes [25], and cytoskeletal components [16] leading to overt injury or to apoptosis [11]. Lipid peroxides, derived aldehydes and cholesterol oxides are postulated as likely causative agents [7,9].