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Benjamin J Ansell

Publications and source records attributed to Benjamin J Ansell.

16 recordsLinked to original sources
PubMed2007

Modifying the anti-inflammatory effects of high-density lipoprotein.

The anti-inflammatory effects of high-density lipoproteins (HDL) are well documented and include inhibition of low-density lipoprotein (LDL) oxidation, reduction of inflammatory cytokines and vascular leukocyte adhesion molecules, and participation in innate immunity. However, certain conditions, including coronary disease, diabetes mellitus, systemic inflammation, and a diet high in saturated fat, are associated with modification of HDL such that it paradoxically enhances LDL oxidation and/or vascular inflammation. Treatment with statins and/or apolipoprotein A1 mimetic peptides improves HDL's anti-inflammatory functions, and these as well as other medications may represent a novel pathway through which to target atherosclerosis.

Humans↗
PubMed2006

High-density lipoprotein: is it always atheroprotective?

High-density lipoproteins (HDLs) are appropriately recognized for their many atheroprotective functions, including reverse cholesterol transport, as well as antioxidant, anti-inflammatory, and antithrombotic effects. Furthermore, the inverse relationship between HDL cholesterol and atherosclerosis is well documented in many populations. However, there is an increasing body of evidence that there are circumstances in which HDL may not be protective, and may in fact paradoxically promote vascular inflammation and oxidation of low-density lipoproteins. Recent studies have provided insight as to specific chemical modifications and structural changes within HDL associated with this phenotype. The presence of proinflammatory HDL coincides with conditions associated with chronic systemic inflammation, including atherosclerosis.

Anticholesteremic Agents↗
PubMed2006

Reduced treatment success in lipid management among women with coronary heart disease or risk equivalents: results of a national survey.

BACKGROUND: This survey assessed and compared National Cholesterol Education Program (NCEP) Third Adult Treatment Panel lipid treatment goal achievement for men versus women undergoing treatment of dyslipidemia. METHODS: Patients receiving treatment for dyslipidemia from physicians (N = 376) in the United States who were high prescribers of lipid medications were enrolled in the NCEP Evaluation Project Utilizing Novel E-Technology (NEPTUNE) II. Data from a single office visit were collected and entered into the NEPTUNE software on a personal digital assistant and uploaded to a central database via the Internet. RESULTS: Of the 4885 patients evaluated, 2103 (43%) were women. NCEP Third Adult Treatment Panel low-density lipoprotein cholesterol (LDL-C) goal achievement was similar between women and men with 0 or 1 risk factor (89% and 88%, respectively) and 2 or more risk factors (75% and 76%, respectively). However, fewer women than men achieved goal in the coronary heart disease and risk equivalents (CHD + CHD RE) category (50% vs 60%, respectively; P < .001). Logistic regression analyses examining the association between sex and LDL-C treatment goal achievement, and evaluating potential confounding by other predictors of treatment success, indicated an age-adjusted odds ratio of 0.66 (95% confidence interval, 0.56-0.77; P < .001) and a multivariate odds ratio of 0.76 (95% confidence interval, 0.62-0.93; P = .009) for women compared with men in the CHD + CHD RE category. CONCLUSIONS: Female sex was associated with lower likelihood of LDL-C goal achievement among patients with CHD + CHD RE. This relationship remained significant after adjustment for other significant predictors of treatment success.

Anticholesteremic Agents↗
PubMed2006

Mechanisms of disease: proatherogenic HDL--an evolving field.

It is well known that, in large populations, HDL-cholesterol levels are inversely related to the risk of atherosclerotic clinical events; however, in an individual, the predictive value of an HDL-cholesterol level is far from perfect. As a result, other HDL-associated factors have been investigated, including the quality and function of HDL in contradistinction to the level of HDL-cholesterol. Regarding their quality, HDL particles are highly heterogeneous and contain varying levels of antioxidants or pro-oxidants, which results in variation in HDL function. It has been postulated that HDL functions to promote reverse cholesterol transport. Recent studies support this role for HDL but also indicate that HDL is a modulator of systemic inflammation. In the absence of inflammation, HDL has a complement of antioxidant enzymes that work to maintain an anti-inflammatory state. In the presence of systemic inflammation, these antioxidant enzymes can be inactivated and HDL can accumulate oxidized lipids and proteins that make it proinflammatory. Under these conditions the main protein of HDL, apolipoprotein A-I, can be modified by reactive oxygen species. This modification impairs the ability of HDL to promote cholesterol efflux by the ATP-binding cassette transporter A-1 pathway. Animal studies and small-scale human studies suggest that measures of the quality and novel functions of HDL might provide an improved means of identifying subjects at increased risk for atherosclerotic events, compared with the current practice of only measuring HDL-cholesterol levels. The quality and function of HDL are also attractive targets for emerging therapies.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2005

High-density lipoprotein function recent advances.

Although high-density lipoproteins (HDL) possess many features that contribute to the association between elevated HDL cholesterol and protection from atherosclerosis, these lipoproteins may be modified in certain individuals and/or circumstances to become proinflammatory. The ability of HDL to inhibit or paradoxically to enhance vascular inflammation, lipid oxidation, plaque growth, and thrombosis reflects changes in specific enzyme and protein components. The anti-inflammatory and proinflammatory functional properties of HDL can now be assessed using cell-based and cell-free assays. Acute or chronic systemic inflammation and the metabolic syndrome appear to render HDL proinflammatory. In contrast, statins and experimental agents such as apolipoprotein A-1 mimetics render HDL more anti-inflammatory. Functional characterization of HDL is a promising method for enhanced assessment of cardiovascular risk and effectiveness of risk reduction.

Animals↗
PubMed2005

Results of the National Cholesterol Education (NCEP) Program Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II survey and implications for treatment under the recent NCEP Writing Group recommendations.

The most recent national survey of compliance with the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) guidelines was completed before ATP III and showed significant underachievement of low-density lipoprotein (LDL) cholesterol goals. The NCEP Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II was a national survey conducted in 2003. Of the 4,885 patients, 67% achieved their LDL cholesterol treatment goal, including 89%, 76%, and 57%, respectively, in the 0 or 1 risk factor, > or = 2 risk factors or coronary heart disease (CHD), and CHD risk equivalent categories. The percentage with triglyceride concentrations > or = 200 mg/dl (2.25 mmol/L) in each risk category who achieved their LDL cholesterol and non-high-density lipoprotein cholesterol goals was 64%, 52%, and 27%, respectively. Patients with diabetes (55%) and other CHD risk equivalents (40%) were less likely to have achieved their LDL cholesterol targets than those with CHD (62%). Of the 1,447 patients with cardiovascular disease, 75% could be classified as very high risk according to the new July 2004 NCEP Writing Group recommendations, and 17.8% of those at very high risk had an LDL cholesterol level of <70 mg/dl (<1.81 mmol/L). In conclusion, these results suggest improved lipid management compared with previous surveys. The largest treatment gaps were found for features new to ATP III as of July 2004, including goal achievement for patients with CHD risk equivalents and for non-high-density lipoprotein cholesterol targets. Most of those (75%) with cardiovascular disease in NEPTUNE II would be considered very high risk and candidates for aggressive therapy to reach the new optional treatment goals.

Anticholesteremic Agents↗
PubMed2005

Apolipoprotein A-I mimetic peptides.

Despite identical amino acid composition, differences in class A amphipathic helical peptides caused by differences in the order of amino acids on the hydrophobic face results in substantial differences in antiinflammatory properties. One of these peptides is an apolipoprotein A-I (apoA-I) mimetic, D-4F. When given orally to mice and monkeys, D-4F caused the formation of pre-beta high-density lipoprotein (HDL), improved HDL-mediated cholesterol efflux, reduced lipoprotein lipid hydroperoxides, increased paraoxonase activity, and converted HDL from pro-inflammatory to antiinflammatory. In apolipoprotein E (apoE)-null mice, D-4F increased reverse cholesterol transport from macrophages. Oral D-4F reduced atherosclerosis in apoE-null and low-density lipoprotein (LDL) receptor-null mice. In vitro when added to human plasma at nanomolar concentrations, D-4F caused the formation of pre-beta HDL, reduced lipoprotein lipid hydroperoxides, increased paraoxonase activity, and converted HDL from pro-inflammatory to antiinflammatory. Physical-chemical properties and the ability of various class A amphipathic helical peptides to activate lecithin cholesterol acyltransferase (LCAT) in vitro did not predict biologic activity in vivo. In contrast, the use of cultured human artery wall cells in evaluating these peptides was more predictive of their efficacy in vivo. We conclude that the antiinflammatory properties of different class A amphipathic helical peptides depends on subtle differences in the configuration of the hydrophobic face of the peptides, which determines the ability of the peptides to sequester inflammatory lipids. These differences appear to be too subtle to predict efficacy based on physical-chemical properties alone. However, understanding these physical-chemical properties provides an explanation for the mechanism of action of the active peptides.

Animals↗
PubMed2005

Rationale for combination therapy with statin drugs in the treatment of dyslipidemia.

Although statin therapy is a mainstay of lipid treatment, complementary effects of other cholesterol-lowering therapies modify the lipid panel and other aspects of coronary disease risk. These other therapies lower low-density lipoprotein cholesterol and triglycerides and/or raise high-density lipoprotein cholesterol, improve diabetic control, and modify other cardiovascular risks. Historically, combination therapy has been reserved for the small minority of patients with severe dyslipidemia, due to perceived risk. More recently, however, it has been recognized that the potential complications of this combination are far outweighed by the clinical benefits that are possible.

Anion Exchange Resins↗
PubMed2005

Evidence for a combined approach to the management of hypertension and dyslipidemia.

The recognition that hypertension and dyslipidemia coexist more often than would be expected by chance and that their combination increases the risk of coronary heart disease (CHD) has important implications for patient management. Patients with cardiovascular disease (CVD) and healthy individuals with multiple CVD risk factors--including concomitant dyslipidemia and hypertension-are the primary focus of updated treatment guidelines for CVD prevention. There is a need for a treatment paradigm shift from the diagnosis and treatment of individual CVD risk factors to the assessment and management of total CVD risk. Goals for each CVD risk factor need to be intensified when multiple sources of risk are present. Patients who have no overt disease but who have multiple CVD risk factors are now understood to be at high risk and should be the target of aggressive primary preventive strategies to avert unnecessary morbidity and mortality. It is also becoming clear that CVD risk factors interact at the level of the endothelium to promote atherosclerosis. Furthermore, recent clinical trials, including those assessing atherosclerotic progression and CVD endpoints, have demonstrated the effectiveness of interventions targeted at multiple risk factors for CVD.

Antihypertensive Agents↗
PubMed2005

The double jeopardy of HDL.

The ability of high-density lipoprotein (HDL) to promote cholesterol efflux is thought to be important in its protection against cardiovascular disease. Anti-inflammatory properties of HDL have emerged as additional properties that may also be important. HDL appears to have evolved as part of the innate immune system functioning to inhibit inflammation in the absence of an acute phase response (APR) but functioning to increase inflammation in the presence of an APR. Inbred strains of mice that are genetically susceptible to atherosclerosis have pro-inflammatory HDL, while inbred strains that are resistant to atherosclerosis have anti-inflammatory HDL. In one small study, humans with coronary heart disease (CHD) or CHD equivalents had pro-inflammatory HDL prior to statin therapy and about half continued to have pro-inflammatory HDL after statin therapy despite a profound decrease in plasma lipids. Pro-inflammatory HDL was relatively weak in its ability to promote cholesterol efflux while anti-inflammatory HDL was better in promoting cholesterol efflux. In other studies, oxidative alterations of the major protein of HDL, apolipoprotein A-I (apoA-I), impaired the ability of the apoA-I to promote cholesterol efflux. Thus, HDL structure and function may be more important than HDL-cholesterol levels in predicting risk for cardiovascular disease.

Animals↗
PubMed2004

The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL.

For more than two decades, there has been continuing evidence of lipid oxidation playing a central role in atherogenesis. The oxidation hypothesis of atherogenesis has evolved to focus on specific proinflammatory oxidized phospholipids that result from the oxidation of LDL phospholipids containing arachidonic acid and that are recognized by the innate immune system in animals and humans. These oxidized phospholipids are largely generated by potent oxidants produced by the lipoxygenase and myeloperoxidase pathways. The failure of antioxidant vitamins to influence clinical outcomes may have many explanations, including the inability of vitamin E to prevent the formation of these oxidized phospholipids and other lipid oxidation products of the myeloperoxidase pathway. Preliminary data suggest that the oxidation hypothesis of atherogenesis and the reverse cholesterol transport hypothesis of atherogenesis may have a common biological basis. The levels of specific oxidized lipids in plasma and lipoproteins, the levels of antibodies to these lipids, and the inflammatory/anti-inflammatory properties of HDL may be useful markers of susceptibility to atherogenesis. Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides may both promote a reduction in oxidized lipids and enhance reverse cholesterol transport and therefore may have therapeutic potential.

Animals↗
PubMed2003

Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment.

BACKGROUND: The inflammatory/antiinflammatory properties of HDL were compared with HDL cholesterol in 2 groups of patients and in age- and sex-matched control subjects. METHODS AND RESULTS: Group 1 consisted of 26 patients not yet taking a statin who presented with coronary heart disease (CHD) or CHD equivalents by National Cholesterol Education Program Adult Treatment Panel III criteria studied before and 6 weeks after 40 mg/d of simvastatin. Group 2 consisted of 20 patients with documented CHD and HDL cholesterol > or =84 mg/dL. The inflammatory/antiinflammatory properties of HDL were determined by the ability of the subject's HDL to alter LDL-induced monocyte chemotactic activity (MCA) in a human artery wall coculture. Induction of MCA by a control LDL was determined in the absence or presence of the subject's HDL. Values in the absence of HDL were normalized to 1.0. Values >1.0 after the addition of HDL indicated proinflammatory HDL; values <1.0 indicated antiinflammatory HDL. Group 1 values before simvastatin were LDL cholesterol, 118+/-24 mg/dL; HDL cholesterol, 57+/-13 mg/dL; triglycerides, 125+/-64 mg/dL; and high-sensitivity C-reactive protein (hs-CRP), 1.7+/-1.9 mg/L; and MCA values were 1.38+/-0.91, compared with 0.38+/-0.14 for control subjects (P=1.5x10(-5)). After simvastatin, values were LDL cholesterol, 73+/-24 mg/dL; HDL cholesterol, 61+/-14 mg/dL; triglycerides, 99+/-52 mg/dL; and hs-CRP, 1.3+/-1.3 mg/L; and MCA values were 1.08+/-0.71. In group 2, values were LDL cholesterol, 108+/-34 mg/dL; HDL cholesterol, 95+/-14 mg/dL; triglycerides, 89+/-44 mg/dL; and hs-CRP, 0.8+/-0.7 mg/L; and MCA values were 1.28+/-0.29, compared with 0.35+/-0.11 for control subjects (P=1.7x10(-14)). Similar results were obtained with the cell-free assay. CONCLUSIONS: The inflammatory/antiinflammatory properties of HDL distinguished patients from control subjects better than HDL cholesterol and were improved with simvastatin.

Adult↗
PubMedDate not supplied

hsCRP and HDL effects of statins trial (CHEST): rapid effect of statin therapy on C-reactive protein and high-density lipoprotein levels A clinical investigation.

Inflammation contributes to the pathogenesis of coronary heart disease and elevated serum levels of C-reactive protein (CRP) are independently associated with increased coronary risk. This study assessed whether there were differences in the effects on CRP and high-density lipoprotein (HDL) cholesterol levels among patients treated with three common statins. In a prospective, observational study, 80 dyslipidemic adults without evidence of cardiovascular disease were treated with 10 mg atorvastatin (A), 20 mg simvastatin (S), or 40 mg pravastatin (P) daily. CRP and lipid profiles were assayed before and after 12 weeks of therapy; in 21 patients, CRP levels were also measured after 1 and 4 weeks. The three treatment groups experienced comparable reductions in CRP (A: 33%, S: 42%, and P: 30%) and statistically insignificant changes in HDL cholesterol levels. CRP began to decrease after 1 week of treatment, and decreased further at 4 and 12 weeks of therapy. The change in the log-transformed CRP concentration correlated with the change in the log-transformed LDL cholesterol concentration. Subjects had similar baseline CRP levels, lipid profiles, and coronary risk factors. The authors conclude that at doses achieving similar reductions in LDL cholesterol, the three statins were associated with comparable decreases in CRP without significant changes in HDL cholesterol levels. The correlation between the reductions in CRP and LDL cholesterol differs from the findings of other published studies, and should prompt further investigation of the mechanism by which statins reduce CRP.

Anticholesteremic Agents↗