scholarly journals Angiopoietin-Like Protein 3 (ANGPTL3) Modulates Lipoprotein Metabolism and Dyslipidemia

2021 ◽  
Vol 22 (14) ◽  
pp. 7310
Author(s):  
Pei-Yi Chen ◽  
Wan-Yun Gao ◽  
Je-Wen Liou ◽  
Ching-Yen Lin ◽  
Ming-Jiuan Wu ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Plasma Levels ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Loss Of Function ◽  
Potential Strategy

Dyslipidemia is characterized by increasing plasma levels of low-density lipoprotein-cholesterol (LDL-C), triglycerides (TGs) and TG-rich lipoproteins (TGRLs) and is a major risk factor for the development of atherosclerotic cardiovascular disorders (ASCVDs). It is important to understand the metabolic mechanisms underlying dyslipidemia to develop effective strategies against ASCVDs. Angiopoietin-like 3 (ANGPTL3), a member of the angiopoietin-like protein family exclusively synthesized in the liver, has been demonstrated to be a critical regulator of lipoprotein metabolism to inhibit lipoprotein lipase (LPL) activity. Genetic, biochemical, and clinical studies in animals and humans have shown that loss of function, inactivation, or downregulated expression of ANGPTL3 is associated with an obvious reduction in plasma levels of TGs, LDL-C, and high-density lipoprotein-cholesterol (HDL-C), atherosclerotic lesions, and the risk of cardiovascular events. Therefore, ANGPTL3 is considered an alternative target for lipid-lowering therapy. Emerging studies have focused on ANGPTL3 inhibition via antisense oligonucleotides (ASOs) and monoclonal antibody-based therapies, which have been carried out in mouse or monkey models and in human clinical studies for the management of dyslipidemia and ASCVDs. This review will summarize the current literature on the important role of ANGPTL3 in controlling lipoprotein metabolism and dyslipidemia, with an emphasis on anti-ANGPTL3 therapies as a potential strategy for the treatment of dyslipidemia and ASCVDs.

scholarly journals U-Shaped Relationship of Low-Density Lipoprotein Cholesterol With Risk of Severe COVID-19 From a Multicenter Pooled Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiao Gong ◽  
Yaqiong Chen ◽  
Yusheng Jie ◽  
Mingkai Tan ◽  
Zhaofang Jiang ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Odds Ratios ◽  
Lowering Therapy ◽  
Severe Group

Low-density lipoprotein cholesterol (LDL-C) is a well-known risk factor for coronary heart disease but protects against infection and sepsis. We aimed to disclose the exact association between LDL-C and severe 2019 novel coronavirus disease (COVID-19). Baseline data were retrospectively collected for 601 non-severe COVID-19 patients from two centers in Guangzhou and one center in Shenzhen, and patients on admission were medically observed for at least 15 days to determine the final outcome, including the non-severe group (n = 460) and the severe group (severe and critical cases) (n = 141). Among 601 cases, 76 (12.65%) received lipid-lowering therapy; the proportion of patients taking lipid-lowering drugs in the severe group was higher than that in the non-severe group (22.7 vs. 9.6%). We found a U-shaped association between LDL-C level and risk of severe COVID-19 using restricted cubic splines. Using univariate logistic regression analysis, odds ratios for severe COVID-19 for patients with LDL-C ≤1.6 mmol/L (61.9 mg/dL) and above 3.4 mmol/L (131.4 mg/dL) were 2.29 (95% confidence interval 1.12–4.68; p = 0.023) and 2.02 (1.04–3.94; p = 0.039), respectively, compared to those with LDL-C of 2.81–3.40 mmol/L (108.6–131.4 mg/dL); following multifactorial adjustment, odds ratios were 2.61 (1.07–6.37; p = 0.035) and 2.36 (1.09–5.14; p = 0.030). Similar results were yielded using 0.3 and 0.5 mmol/L categories of LDL-C and sensitivity analyses. Both low and high LDL-C levels were significantly associated with higher risk of severe COVID-19. Although our findings do not necessarily imply causality, they suggest that clinicians should pay more attention to lipid-lowering therapy in COVID-19 patients to improve clinical prognosis.

Comparison of LDL-C calculation by friedewald and martin/hopkins methods in 12,243 adults from the United States of America

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Penson ◽  
S.S Martin ◽  
N.C Henney ◽  
M Banach
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Threshold Value ◽  
The United States ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Strongly Correlated ◽  
Low Density Lipoprotein Cholesterol

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is an established risk factor for cardiovascular disease (CVD), and a target for lipid-lowering therapy. LDL-C is typically not measured directly but is estimated using the Friedewald formula, which assumes a fixed factor for the ratio of triglycerides (TG) to very low-density lipoprotein cholesterol (VLDL-C). However this assumption is sometimes not valid. The Martin/Hopkins (M/H) formula estimates LDL-C using an adjustable factor for the TG:VLDL-C ratio and is expected to improve upon Friedewald when predicting measured LDL-C, and apolipoprotein B (ApoB), one molecule of which is associated with each LDL particle. Purpose We compared values of LDL-C calculated by the Friedewald and M/H methods with respect to their correlation with non-high density lipoprotein cholesterol (non-HDL-C) and ApoB, and their classification of individuals based upon attainment of the threshold value of 70 mg/dl (1.8 mmol/l) of LDL-C. This cut-point is a treatment target for individuals at high risk of CVD in the 2019 ESC guidelines for lipid modification, and a threshold for initiating statin therapy in the 2019 ACC/AHA guidelines. Methods In this analysis we included participants in the National Health and Nutrition Examination Survey (NHANES) from 2005–2016, age ≥18, <80 years who had measurements for total cholesterol (TC), TG and HDL-C. LDL-C was calculated using Friedewald and M/H. We correlated LDL-C (calculated using the two methods) with non-HDL-C and ApoB. We identified individuals with LDL-C <70 mg/dl using both methods. When LDL-C (Friedewald) was <70, but LDL-C (M/H) was >70, we classified these participants as discordant. Statistical analyses were performed in IBM SPSS for Windows v26. Results 12,243 individuals were included. 51.8% were female, mean (±SD) age was 45.5±17.4, 15.3% were treated with statins, ApoB was available for 2179 participants. Mean lipid concentrations (mg/dl) were: TC: 191.5±41.0, TG: 120.0±67.0, HDL-C: 54.1±15.7, LDL-C (Friedewald): 113.3±35.4; LDL-C (M/H): 114.9±35.2. In the whole population, LDL-C (M/H) was more strongly correlated than LDL-C (Friedewald) with ApoB (r=0.935 v 0.894) and non-HDL-C (r=0.981 v 0.944). In statin-treated participants, LDL-C (M/H) was also more strongly correlated with ApoB (r=0.951 v 0.914) and non-HDL-C (r=0.979 v 0.928). 1139 participants had LDL-C (Friedewald) <70 mg/dl. Of these, 206 individuals (18.1%) were discordant, having LDL-C (M/H) >70 mg/dl. Amongst statin-treated patients, 22.9% were discordant. Only 5.5% of individuals with LDL-C (M/H) <70 mg/dl showed reverse discordance (LDL-C (Friedewald) >70 mg/dl). Conclusions The M/H method of calculating LDL-C correlates more strongly with non-HDL-C and ApoB than Friedewald. Importantly the discordant results confirm previous observations that Friedewald underestimates LDL-C at low concentrations. This may result in under-use of lipid-lowering therapies. Funding Acknowledgement Type of funding source: None

Importance of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the treatment of dyslipidemia and atherosclerosis

2019 ◽  
pp. 40-52
Author(s):  
Maksim Maksimov ◽  
Anastasia Shikaleva ◽  
Aleksandra Kuchaeva
Keyword(s):  
Clinical Studies ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Pcsk9 Inhibitors ◽  
Lipid Lowering Drugs ◽  
Antibody Preparations

Representatives of different groups of lipid-lowering drugs may have some differences in the nature and severity of the effect on the blood lipid spectrum. A new class of drugs, PCSK9 inhibitors, whose activity is associated with a protein involved in the control of low density lipoprotein receptors, has recently appeared. In clinical practice, this group is represented by monoclonal antibody preparations evolocumab and alirocumab. PCSK9 inhibitors are promising drugs for use in combination lipid-lowering therapy, which so far, given the results of clinical studies, can be recommended in the third place after statins and ezetimibe. In clinical studies, it was shown that alirocoumab and evolocumab alone or in combination with statins and/or other lipid-lowering drugs significantly reduce cholesterol levels in low density lipoproteins – by an average of 60%, depending on the dose.

scholarly journals Evaluation and Management of Dyslipidemia in Patients Treated with Lorlatinib

2021 ◽  
Vol 28 (1) ◽  
pp. 265-272
Author(s):  
Normand Blais ◽  
Jean-Philippe Adam ◽  
John Nguyen ◽  
Jean C. Grégoire
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Specific Patient ◽  
Anaplastic Lymphoma ◽  
Lowering Therapy ◽  
Trial Protocols ◽  
Simplified Algorithm

The use of lorlatinib, an anaplastic lymphoma kinase (ALK) inhibitor for the treatment of ALK-positive metastatic non-small cell lung cancer, is associated with dyslipidemia in over 80% of patients. Clinical trial protocols for the management of lorlatinib-associated dyslipidemia differ from clinical practice guidelines for the management of dyslipidemia to prevent cardiovascular disease, in that they are based on total cholesterol and triglyceride levels rather than on the low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol levels that form the basis of current cardiovascular guideline recommendations. In order to simplify and harmonize the management of cardiovascular risk in patients with lorlatinib, an advisory committee consisting of a medical oncologist, a cardiologist, and two pharmacists with expertise in cardiology and oncology aimed to develop a simplified algorithm, adapted from the Canadian Cardiovascular Society dyslipidemia recommendations. Recommendations for the evaluation and management of hypercholesterolemia and isolated hypertriglyceridemia in patients treated with lorlatinib are outlined. These recommendations are based on data collected in a large number of lipid-lowering therapy trials applicable to individuals with and without cancer. Considering the relatively long life expectancy and improving prognosis of patients with ALK translocations, this specific patient population should be treated as are patients without cancer and are likely to derive the same benefits from lipid-lowering therapy.

Abstract 16263: Association Between Visit-to-Visit Lipid Variability and Cardiovascular Events in Patients With Familial Hypercholesterolemia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yexuan Cao ◽  
Ruixia Xu ◽  
Huiwen Zhang ◽  
Jinglu Jin ◽  
Huihui Liu ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Cardiovascular Events ◽  
Prognostic Value ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Major Adverse Cardiovascular Events ◽  
Lipid Lowering Therapy ◽  
Cox Analysis

Introduction: Visit-to-visit variability in lipid has been suggested as an predictor of major adverse cardiovascular events (MACEs). However, no evidence exists on the prognostic value of lipid variability in patients with familial hypercholesterolemia (FH). Hypothesis: This prospective cohort study aimed to investigate whether lipid variability affects future MACEs in patients with FH receiving standard lipid-lowering therapy. Methods: A total of 254 patients with FH were consecutively enrolled and followed for MACEs. Variability in triglyceride, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] were evaluated from 3 months after discharge using the standard deviation (SD), coefficient of variation (CV) and variability independent of the mean (VIM). Results: During a mean follow-up of 49 months, 22 (8.7%) events occurred. Visit-to-visit variability in Lp(a) was significantly higher in the MACE group compared to the non-MACE group. In multivariate Cox analysis, only Lp(a) variability parameters were independent predictors for MACEs. The hazard ratios and 95% confidence intervals of each 1-SD increase of SD, CV and VIM of Lp(a) were 1.42 (1.12-1.80), 1.50 (1.11-2.02) and 1.60 (1.16-2.22), respectively. Kaplan-Meier analysis revealed that patients with higher Lp(a) variability presented lower event-free survival (Log-rank p <0.05). The results were consistent in various subgroups. Conclusions: This is the first report to evaluate the prognostic value of lipid variability in real-world patients with FH and showed that Lp(a), but not LDL-C variability, was associated with MACEs, which emphasized the importance of regular lipid monitoring in patients with high risk.

scholarly journals Lipid Management in Patients Presenting With Acute Coronary Syndromes: A Review

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Bimmer E. Claessen ◽  
Paul Guedeney ◽  
C. Michael Gibson ◽  
Dominick J. Angiolillo ◽  
Davide Cao ◽  
...  
Keyword(s):  
Secondary Prevention ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipid Management ◽  
Current State

Abstract Despite many improvements in its prevention and management, acute coronary syndrome (ACS) remains a major cause of morbidity and mortality in the developed world. Lipid management is an important part of secondary prevention after ACS, but many patients currently remain undertreated and do not attain guideline‐recommended levels of low‐density lipoprotein cholesterol reduction. This review details the current state of evidence on lipid management in patients presenting with ACS, provides directions for identification of patients who may benefit from early escalation of lipid‐lowering therapy, and discusses novel lipid‐lowering medication that is currently under investigation in clinical trials. Moreover, a treatment algorithm aimed at attaining guideline‐recommended low‐density lipoprotein cholesterol levels is proposed. Despite important advances in the initial treatment and secondary prevention of ACS, ≈20% of ACS survivors experience a subsequent ischemic cardiovascular event within 24 months, and 5‐year mortality ranges from 19% to 22%. Knowledge of the current state of evidence‐based lipid management after ACS is of paramount importance to improve outcomes after ACS.

Lipid-Lowering Therapy and Low-Density Lipoprotein Cholesterol (LDL-C) Goal Achievement in High-Cardiovascular-Risk Patients in Fuzhou, China

2020 ◽  
Vol 25 (4) ◽  
pp. 307-315 ◽  
Author(s):  
Xing Wang ◽  
Yan He ◽  
Tao Wang ◽  
Chunming Li ◽  
Zihui Ma ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
High Intensity ◽  
Index Date ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Purpose: This study aims to analyze the treatment patterns and goal attainment of low-density lipoprotein cholesterol (LDL-C) among patients with atherosclerotic cardiovascular disease (ASCVD) and diabetes mellitus (DM) in the real-world setting in Fuzhou, China. Methods: Patients aged ≥20 years with a valid LDL-C measurement (index date) in 2016 were selected from National Healthcare Big Data in Fuzhou, China. Patients were stratified into mutually exclusive cardiovascular risk categories: ASCVD (including recent acute coronary syndrome [ACS], chronic coronary heart disease [CHD], stroke, and peripheral arterial disease [PAD]), and DM alone (without ASCVD). Lipid-modifying medication and LDL-C attainment at the index date were assessed. Results: A total of 21 989 patients met the inclusion criteria, including 17 320 (78.8%) with ASCVD and 4669 (21.2%) with DM alone; 47.7% of patients received current statin therapy in the overall cohort (53.5% in ASCVD, 26.5% for DM); 20.5% ASCVD population achieved LDL-C target with the highest in patients with recent ACS (33.8%), followed by chronic CHD (21.2%), PAD (20.9%), and ischemic stroke (17.3%); 49.0% of patients with DM achieved LDL-C target. Higher LDL-C attainment was observed in high-intensity statin and a combination of statin and nonstatin groups. Atorvastatin was the most commonly used statin with the highest LDL-C attainment, followed by rosuvastatin. Conclusion: Compared with previous studies in China, our study found a relatively low statin use and LDL-C target attainment, but higher than similar studies in Europe. Guidelines should be well complied and more prescription of high-intensity statin or statin and nonstatin combination should be advocated.

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