We measured cholesterol efflux capacity in 203 healthy volunteers who underwent assessment of carotid artery intima–media thickness, 442 patients with angiograph ically confirmed coronary artery disease, and 351 patients without such angiographically confirmed disease. We quantified efflux capacity by using a validated ex vivo system that involved incubation of macrophages with apolipoprotein B–depleted serum from the study participants. Results The levels of HDL cholesterol and apolipoprotein A-I were significant determinants of cholesterol efflux capacity but accounted for less than 40% of the observed variation. An inverse relationship was noted between efflux capacity and carotid intima–media thickness both before and after adjustment for the HDL cholesterol level. Furthermore, efflux capacity was a strong inverse predictor of coronary disease status (adjusted odds ratio for coronary disease per 1-SD increase in efflux capacity, 0.70; 95% confidence interval [CI], 0.59 to 0.83; P<0.001). This relationship was attenuated, but remained significant, after additional adjustment for the HDL cholesterol level (odds ratio per 1-SD increase, 0.75; 95% CI, 0.63 to 0.90; P = 0.002) or apolipoprotein A-I level (odds ratio per 1-SD increase, 0.74; 95% CI, 0.61 to 0.89; P = 0.002). Additional studies showed enhanced efflux capacity in patients with the metabolic syndrome and low HDL cholesterol levels who were treated with pioglitazone, but not in patients with hypercholesterolemia who were treated with statins. Conclusions Cholesterol efflux capacity from macrophages, a metric of HDL function, has a strong inverse association with both carotid intima–media thickness and the likeli hood of angiographic coronary artery disease, independently of the HDL cholesterol level. (Funded by the National Heart, Lung, and Blood Institute and others.)

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Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis

Aim:There currently does not exist guidance for authors aiming to undertake systematic reviews of observational epidemiological studies, such as those reporting prevalence and incidence information. These reviews are particularly useful to measure global disease burden and changes in disease

Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data.

RELIABLE ASSESSMENT OF THE separate and joint associations of major blood lipids and apolipoproteins with the risk of vascular disease is important for the development of screening and therapeutic strategies. Expert opinion is divided about whether assessment of apolipoprotein AI (apo AI) and apolipoprotein B (apo B) should replace assessment of high-density lipoprotein cholesterol (HDL-C) and total cholesterol levels in assessment of vascular risk. Althoughthere isagreementabout the valueofreducinglow-densitylipoprotein cholesterol (LDL-C or, approximately analogously,non–high-density lipoprotein cholesterol [non–HDL-C]), uncertainty persists about the merits of modification or measurement of triglycerides orHDL-C.Therearestronglypositiveepidemiological associationsof triglyceride concentration with risk of vascular disease, but it is not clear to what extent theserelationshipsdependoncholesterol levels or vary with fasting state. Similarly, although previous analyses have generally reported inverse associations of HDL-C with risk of vascular disease, many studies have not investigated the extent to which they depend on triglyceride concentration. The failure of torcetrapib has raised questions about the value of raising HDL-C and highlighted the need to characterize more reliably the relationship between HDL-C and vascular risk, particularly at high HDL-C levels. Different uncertainties apply in relation to the risk of ischemic stroke and the cholesterol content of proatherogenic lipoproteins. The reduction in ischemic stroke in randomized trials of statins (which principally lower LDL-C) is remarkable in light of the weak epidemiological association reported between circulating LDL-C concentration and ischemic stroke, suggesting the need for more powerful and detailed prospective analyses of blood lipids and stroke subtypes. The objective of this report is to produce reliable estimates of the associations of major lipids and apolipoproteins in relation to coronary heart disease (CHD) and ischemic stroke, incorporating adjustment for confounding caused by other risk factors and correction for regression dilution.

Major Lipids, Apolipoproteins, and Risk of Vascular Disease

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal.

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Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

This brief summarizes the results of a gender impact evaluation study, entitled Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting : a randomized controlled trial of text message reminders, conducted between June 2007 to August 2008 in Kenya. The study observed that there is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy (ART). This study tested the efficacy of short message service (SMS) reminders on adherence to ART among patients attending a rural clinic in Kenya. In intention-to-treat analysis, 53 percent of participants receiving weekly SMS reminders achieved adherence of at least 90 percent during the 48 weeks of the study, compared with 40 percent of participants in the control group, the difference is significant. Funding for the study derived from the World Bank Research Group, Bank-Netherlands Partnership Program, USAID AMPATH Partnership, National Institute of Mental Health.

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Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting : a randomized controlled trial of text message reminders

Ontario HIV Treatment
Network; Canadian Institutes for Health Research; National Institues of Health (AI005535901, K23A106858201, AA015287, MH54907, AI27763); British Columbia Michael Smith Foundation; The Doris Duke Charitable Foundation

https://www.ghdonline.org/uploads/Adherence_to_HAART_A_Systematic_Review_of_Developed_and_Developing_Nation_Patient-Reported_Barriers_and_Facilitators_.pdf

Adherence to HAART: A Systematic Review of Developed and Developing Nation Patient-Reported Barriers and Facilitators

Objective To investigate the association between treatment induced change in high density lipoprotein cholesterol and total death, coronary heart disease death, and coronary heart disease events (coronary heart disease death and non-fatal myocardial infarction) adjusted for changes in low density lipoprotein cholesterol and drug class in randomised trials of lipid modifying interventions. Design Systematic review and meta-regression analysis of randomised controlled trials. Data sources Medline, Embase, Central, CINAHL, and AMED to October 2006 supplemented by contact with experts in the field. Study selection In teams of two, reviewers independently determined eligibility of randomised trials that tested lipid modifying interventions to reduce cardiovascular risk, reported high density lipoprotein cholesterol and mortality or myocardial infarctions separately for treatment groups, and treated and followed participants for at least six months. Data extraction and synthesis Using standardised, pre-piloted forms, reviewers independently extracted relevant information from each article. The change in lipid concentrations for each trial and the weighted risk ratios for clinical outcomes were calculated. Results The meta-regression analysis included 108 randomised trials involving 299 310 participants at risk of cardiovascular events. All analyses that adjusted for changes in low density lipoprotein cholesterol showed no association between treatment induced change in high density lipoprotein cholesterol and risk ratios for coronary heart disease deaths, coronary heart disease events, or total deaths. With all trials included, change in high density lipoprotein cholesterol explained almost no variability ( Conclusions Available data suggest that simply increasing the amount of circulating high density lipoprotein cholesterol does not reduce the risk of coronary heart disease events, coronary heart disease deaths, or total deaths. The results support reduction in low density lipoprotein cholesterol as the primary goal for lipid modifying interventions.

https://www.bmj.com/content/bmj/338/bmj.b92.full.pdf

Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis

Ping-ping Wu

Papers

Adherence to HAART: A Systematic Review of Developed and Developing Nation Patient-Reported Barriers and Facilitators

Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis

Adherence to antiretroviral therapy: A systematic review examining developed and developing nation patient-reported barriers and facilitators.