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.

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.

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

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 (> or =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.

Probucol reduces oxysterol formation in hypertensive rabbits.

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.

Synergistic inhibition of LDL oxidation by phytoestrogens and ascorbic acid.

Increasing evidence indicates that oxidative modification of low-density lipoprotein (LDL) is an important determinant in atherogenesis, and following menopause, the incidence of coronary heart disease is as prevalent in women as it is in men. Estrogen has been demonstrated to inhibit the susceptibility of LDL to be oxidized, and more recently the use of phytoestrogens has been considered for estrogen replacement therapy. In this study the antioxidant activity of the three major phytoestrogens: genistein, daidzein, and equol were measured in terms of LDL oxidative susceptibility.

Correlations between measures of atherosclerosis change using carotid ultrasonography and coronary angiography.

Few studies have examined the correlation between change in carotid artery intima-media thickness (IMT) and change in coronary artery disease. In the Cholesterol Lowering Atherosclerosis Study, current nonsmoking men with coronary artery disease were randomized to colestipol-niacin or placebo. Among 133 subjects with baseline and on-trial coronary angiography and carotid ultrasonography, colestipol-niacin treatment significantly reduced progression of atherosclerosis by both end point measures (2-year average change in percent diameter stenosis by coronary angiography and rate of change in carotid IMT).

Ascorbic acid enhances 17 beta-estradiol-mediated inhibition of oxidized low density lipoprotein formation.

Postmenopausal women who use estrogen appear to be protected from coronary heart disease (CHD). Studies have demonstrated that estrogen can lower low-density lipoprotein (LDL) levels and the antioxidant activity of 17 beta-estradiol can prevent the oxidation of this LDL. Ascorbic acid is regarded as a major hydrophylic antioxidant, however, its impact on the prevention of CHD has yet to be clearly demonstrated.

Serial quantitative coronary angiography and coronary events.

Background: Although assessment of progression of atherosclerosis by quantitative coronary angiography (QCA) is used as a surrogate for coronary events, no validation study has compared the several QCA measures used.

Methods And Results: The Cholesterol Lowering Atherosclerosis Study was a clinical trial testing the efficacy of colestipol-niacin on the progression of coronary atherosclerosis. Baseline/2-year coronary angiograms were obtained on 156 men with prior coronary artery bypass graft surgery.

Cholesterol oxidation products induce vascular foam cell lesion formation in hypercholesterolemic New Zealand white rabbits.

Circulating cholesterol oxidation products (ChOx) have long been implicated in the etiology of early atherosclerosis; however, direct in vivo evidence elucidating their role in atherogenesis is only recently becoming available. This study investigated ChOx effects on vascular lesion formation in New Zealand White rabbits under controlled hypercholesterolemic conditions. By closely monitoring plasma cholesterol levels and adjusting dietary cholesterol intake during a 78-day period, total plasma cholesterol exposures (cumulative plasma cholesterol levels over time) were controlled between 27 000 and 34 000 mg/dLxday (final plasma cholesterol concentration, 467+/-77 mg/mL), representing a threshold range for sudanophilic lesion formation in the aorta.

Pathophysiology of triglyceride-rich lipoproteins in atherothrombosis: clinical aspects.

Invasive and noninvasive arterial imaging are important techniques used to study atherosclerosis and, specifically, to evaluate the atherogenecity of triglyceride-rich lipoproteins (TRL). Serial coronary angiography trials show significant benefit from lowering low-density lipoprotein cholesterol (LDL-C) which serves to retard lesion progression. Even with aggressive LDL-C reduction, however, up to half of patients demonstrate continued progression of atherosclerosis.

Arterial injury by cholesterol oxidation products causes endothelial dysfunction and arterial wall cholesterol accumulation.

Cholesterol oxidation products (ChOx) have been reported to cause acute vascular injury in vivo; however, the pharmacokinetics of ChOx after administration and the mechanisms by which they cause chronic vascular injury are not well understood. To further study the pharmacokinetics and atherogenic properties of ChOx, New Zealand White rabbits were injected intravenously (70 mg per injection, 20 injections per animal) with a ChOx mixture having a composition similar to that found in vivo during a 70-day period. Total ChOx concentrations in plasma peaked almost immediately after a single injection, declined rapidly, and returned to preinjection levels in 2 hours.

Triglyceride-rich lipoproteins and progression of atherosclerosis.

Aims: To present data from the Cholesterol Lowering Atherosclerosis Study (CLAS) and the Monitored Atherosclerosis Regression Study (MARS) demonstrating the relationship between triglyceride-rich lipoproteins and progression of atherosclerosis.

Methods And Results: CLAS and MARS were randomized, placebo-controlled, arterial imaging trials designed to determine the effects of lipid lowering on the progress of atherosclerosis using coronary angiographic and carotid arterial wall intima-media thickness measurement end points. Included in each of these trials were specific measurements of triglyceride-rich lipoproteins in addition to the traditional lipid measurements.

The role of carotid arterial intima-media thickness in predicting clinical coronary events.

Background: Carotid arterial intima-media thickness is used as a noninvasive surrogate end point to measure progression of atherosclerosis, but its relation to coronary events has not been fully explored.

Objective: To determine whether carotid arterial intima-media thickness predicts coronary events.

Design: Long-term follow-up (average, 8.

Intermediate-density lipoproteins and progression of carotid arterial wall intima-media thickness.

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).

A comparison of quantitative computerized and human panel coronary endpoint measures: implications for the design of angiographic trials.

The Monitored Atherosclerosis Regression Study was a double-blind, 2-year, placebo-controlled, randomized, serial angiographic trial which tested reduction of low density lipoprotein-cholesterol with monotherapy using lovastatin on the progression of coronary atherosclerosis. Angiographic outcome was evaluated both by a panel of human readers who visually inspected matched film pairs to arrive at a global change score and by automated computerized vessel edge finding and lesion measurement (quantitative coronary angiography, QCA). In this paper, we model the association between QCA measures of coronary artery lesion change and the panel-based global change score.

The role of triglyceride-rich lipoprotein families in the progression of atherosclerotic lesions as determined by sequential coronary angiography from a controlled clinical trial.

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.

Influence of lifestyle modification on atherosclerotic progression determined by ultrasonographic change in the common carotid intima-media thickness.

The Monitored Atherosclerosis Regression Study (MARS) was a randomized, double-blind, placebo-controlled angiographic trial of lipid-lowering therapy in subjects with coronary artery disease. Subjects were counseled to follow a low-fat, low-cholesterol diet. At every clinic visit, data were obtained on body weight, dietary intake, alcohol consumption, and tobacco use.

LDL- is a lipid hydroperoxide-enriched circulating lipoprotein.

A subclass of LDL described on the basis of its greater electronegativity and oxidative status is further characterized using a new, highly sensitive single photon counting technique to measure lipid hydroperoxides. We describe in this report that these particles, which we refer to as LDL-, are enriched in lipid peroxides and other peroxidation products as compared to the bulk of the unmodified, normal LDL (nLDL) recovered from human plasma. This chemiluminescence-based, single photon counting technique has unique advantages in that analyses are performed on whole LDL, thus avoiding artifactual lipid peroxidation during lipid extraction.

Cardioprotective effects of individual conjugated equine estrogens through their possible modulation of insulin resistance and oxidation of low-density lipoprotein.

Objective: To examine the independent effects on insulin sensitivity and antioxidative activity of the three most prevalent constituents in Premarin (Wyeth-Ayerst Laboratories, Philadelphia, PA): estrone sulfate (E1S), 50%; equilin sulfate (EqS), 25%, and 17 alpha-dihydroequilin sulfate (17 alpha-ES), 15%.

Design: Prospective randomized cross-over study.

Setting: University of Southern California Medical Center.

Effect of supplementary antioxidant vitamin intake on carotid arterial wall intima-media thickness in a controlled clinical trial of cholesterol lowering.

Background: There is accumulating experimental, epidemiological, and clinical evidence of an association between anti-oxidant vitamin intake and reduced risk of coronary heart disease. Using data from the Cholesterol Lowering Atherosclerosis Study (CLAS), we explored the association of self-selected supplementary antioxidant vitamin intake on the rate of progression of early preintrusive atherosclerosis.

Methods And Results: CLAS was an arterial imaging trial in which nonsmoking 40- to 59-year-old men with previous coronary artery bypass graft surgery were randomized to colestipol/niacin plus diet or placebo plus diet.

Probucol suppresses oxidant stress in hypertensive arteries. Immunohistochemical evidence.

Oxy-free radicals may be involved in the pathogenesis of accelerated atherosclerosis in hypertension. We evaluated the direct antioxidant potential of probucol in hypertensive arteries by studying the spatial immunohistochemical distribution of three primary antioxidant enzymes (AEs). Nineteen normocholesterolemic New Zealand White rabbits were divided into two groups: normotensive controls (NT; n = 6) and 13 animals rendered hypertensive by surgical coarctation of abdominal aorta.

Contribution of an in vivo oxidized LDL to LDL oxidation and its association with dense LDL subpopulations.

Oxidative modification of LDL is thought to be a radical-mediated process involving lipid peroxides. The small dense LDL subpopulations are particularly susceptible to oxidation, and individuals with high proportions of dense LDL are at a greater risk for atherosclerosis. An oxidatively modified plasma LDL, referred to as LDL-, is found largely among the dense LDL fractions.