Journal of Vascular Surgery

2018

DOI: 10.1016/j.jvs.2017.11.029

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Effects of Anacetrapib in Patients With Atherosclerotic Vascular Disease

Jemma C. Hopewell²,

et al.

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Rationale For Targeting Cholesterol For Treatment Of Cancer1

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Cited by 126 publications

(152 citation statements)

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“…Over the past few years, there have been multiple large randomized trials investigating the benefits of adding nonstatin agents to statin therapy, including three that evaluated further lowering of LDL cholesterol with ezetimibe (65), PCSK9 inhibitors (66), and, cholesteryl ester transfer protein [CETP] inhibitors, an investigational class of drugs with some recent supportive data (70). Each trial found a significant benefit in the reduction of ASCVD events that was directly related to the degree of further LDL cholesterol lowering.…”

Section: The Risk Calculatormentioning

confidence: 99%

9. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2018

2017

Diabetes Care

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The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

“…Over the past few years, there have been multiple large randomized trials investigating the benefits of adding nonstatin agents to statin therapy, including three that evaluated further lowering of LDL cholesterol with ezetimibe (65), PCSK9 inhibitors (66), and, cholesteryl ester transfer protein [CETP] inhibitors, an investigational class of drugs with some recent supportive data (70). Each trial found a significant benefit in the reduction of ASCVD events that was directly related to the degree of further LDL cholesterol lowering.…”

Section: The Risk Calculatormentioning

confidence: 99%

9. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2018

2017

Diabetes Care

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The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

“…Consequently, it is evident that maintenance of cholesterol homeostasis is vital in maintaining cell proliferation rate, and a key protein that is involved in maintaining this homeostasis both intracellularly (transport cholesterol to storage droplet) as well as extracellularly (net transfer of CEs from HDLs to LDLs) is CETP . Therefore, decreasing LDL levels and increasing HDL levels by targeting CETP has been aggressively tested as a therapeutic option for atherosclerosis and coronary heart disease . Additionally, the lack of CETP has been shown to increase HDL levels and thus promoting direct removal of plasma cholesterol .…”

Section: Rationale For Targeting Cholesterol For Treatment Of Cancermentioning

confidence: 99%

Targeting cellular cholesterol for anticancer therapy

¹

,

²

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³

et al. 2019

The FEBS Journal

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Cholesterol dyshomeostasis in cancer cells leads to intracellular cholesterol accumulation, which imparts drug resistance and allows these cells to evade apoptotic signalling processes and maintain continuous cell division and proliferation. Therefore, cholesterol lowering in cancer cells has been envisaged as a potential anticancer strategy. In this direction, two therapeutic strategies have been proposed: (a) to inhibit the biosynthesis of cholesterol in the cells and (b) to deplete excess cholesterol from cancer cells. In the first phase of this review, we collate the cancer signalling pathways (particularly in breast cancer) that are perturbed by cholesterol dyshomeostasis and highlight recent drug discovery efforts to develop cholesterol‐lowering compounds, some of which are currently under clinical trials. In the second phase, based on the analysis of the available scientific evidence, we conceptualize and argue that the depletion of excess cholesterol could sensitize cancer cells to available therapeutics and may also help to alleviate cancer drug resistance.

“…Observational evidence supports a strong inverse association between high‐density lipoprotein (HDL) cholesterol concentrations and risk of cardiovascular disease (CVD) . However, the inconclusive evidence from large‐scale clinical trials for a cardioprotective effect of HDL cholesterol‐raising agents has cast doubt on the causal relationship between HDL cholesterol and CVD and has suggested that measures of HDL beyond its cholesterol concentration may better capture its functional properties.…”

mentioning

confidence: 99%

High‐Density Lipoprotein Subspecies Defined by Apolipoprotein C‐III and Subclinical Atherosclerosis Measures: MESA (The Multi‐Ethnic Study of Atherosclerosis)

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et al. 2018

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BackgroundApolipoprotein C‐III (apoC‐III), a small proinflammatory protein present on 6% to 7% of high‐density lipoprotein (HDL) particles, defines a subspecies of HDL adversely associated with coronary heart disease in primarily white cohorts. In a multi‐ethnic population free of clinical cardiovascular disease, we evaluated the relationship between apoC‐III–defined HDL subspecies and subclinical markers of atherosclerotic pathology.Methods and ResultsWe investigated cross‐sectional associations between apolipoprotein A‐I concentrations of apoC‐III–defined HDL subspecies, measured via ELISA and imaging measures of subclinical atherosclerosis, among 4659 participants in the MESA (The Multi‐Ethnic Study of Atherosclerosis) at baseline (2000–2002). HDL particles containing and lacking apoC‐III were divergently associated with coronary artery calcification in women (P‐heterogeneity=0.002) but not in men (P‐heterogeneity=0.31) and with carotid plaque score (P‐heterogeneity=0.02) and intima‐media thickness (P‐heterogeneity=0.06) in the overall study population. HDL lacking apoC‐III was inversely associated with all outcome measures (coronary artery calcification, women: odds ratio per SD=0.81 [95% confidence interval [CI], 0.73–0.90]; carotid plaque, overall: odds ratio per SD=0.92 [95% CI, 0.84–1.00]; intima‐media thickness, overall: mean difference per SD=−14.0 µm [95% CI, −21.1 to −6.7 μm]), whereas HDL containing apoC‐III was positively associated (coronary artery calcification, women: odds ratio=1.10 [95% CI, 0.99–1.22]; plaque, overall: odds ratio=1.10 [95% CI, 1.01–1.19]) or unassociated. Neither total HDL nor HDL subspecies was associated with changes in subclinical atherosclerosis measures up to 10 years later.ConclusionsThe presence of apoC‐III defined a subspecies of HDL not inversely associated with baseline measures of subclinical atherosclerosis, supporting a role of apoC‐III in the pathophysiology of cardiovascular disease.

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