scholarly journals Evaluation of Oxidative Stress Status in Familial Hypercholesterolemia

2021 ◽  
Vol 10 (24) ◽  
pp. 5867
Author(s):  
Shiva Ganjali ◽  
Reihaneh Keshavarz ◽  
Susan Hosseini ◽  
Atena Mansouri ◽  
Massimo R. Mannarino ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Healthy Subjects ◽  
Genetic Disorder ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Binary Logistic Regression ◽  
Antioxidant Enzyme Activities ◽  
Oxidative Stress Status ◽  
Antioxidant Markers ◽  
Control Study

Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterizied by elevated levels of circulating low-density lipoprotein cholesterol (LDL-C) which is an important source of substrates to be oxidized by different oxidative agents. Subsequently, the oxidized LDLs (oxLDLs) induce further oxidative reactions in FH patients, which contributes to the development of atherosclerosis and advanced cardiovascular events in these patients. This study aimed to investigate the association of oxidant/antioxidant markers with FH. Methods: This case-control study comprised 18 HoFH, 18 HeFH, and 20 healthy subjects. Oxidant/antioxidant markers including MDA, MPO, thiol, nitric oxide (NO), myeloperoxidase (MPO), glutathione peroxidase (GPx), SOD, and CAT were assessed by colorimetric methods. Prooxidant-antioxidant balance was also measured by pro-oxidant antioxidant balance (PAB) assay. Results: The levels of MDA (p < 0.001), MPO activity (p < 0.001), thiol (p < 0.001), NO (p < 0.01), and PAB (p < 0.001) were notably higher in HoFH group in comparison with healthy subjects. HeFH group also showed significantly higher levels of thiol (p < 0.001) and PAB (p < 0.001) when compared to healthy subjects. Elevated levels of MDA (p < 0.001) and PAB (p < 0.001) were also observed in HoFH relative to HeFH. No significant differences were found between the studied groups in the case of antioxidant enzyme activities. The results of binary logistic regression showed that PAB (OR: 0.979; p = 0.033), and MDA (OR: 0.996; p = 0.018) levels were inversely associated with HoFH, although, after adjustment for age and LDL-C levels, these associations were diminished. Conclusion: Several oxidant/antioxidant differences were found between FH patients and healthy individuals as well as between HoFH and HeFH patients. These differences might be strongly dependent on plasma LDL-C levels.

Abstract 16143: A Novel Clinical Prediction Model for Familial Hypercholesterolemia: Implementation of a Statin-correction Calculator to Enhance Diagnostic Yield

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Zahara A Kanji ◽  
Mohammad S Sheikh ◽  
Daniel Antwi-Amoabeng ◽  
Bryce H Beutler ◽  
Nageshwara Gullapalli ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Familial Hypercholesterolemia ◽  
Diagnostic Yield ◽  
Genetic Disorder ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Clinical Criteria ◽  
Gene Testing ◽  
Whole Exome ◽  
Pre Treatment

Introduction: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder. Individuals with FH have a 22-fold greater risk of early-onset cardiovascular disease as compared to the general population. Early identification of patients with FH is essential to prevent cardiovascular events. Diagnosis may be challenging however for individuals with underlying FH who are already receiving statin therapy, as criteria for FH rely on pre-treatment low-density lipoprotein (LDL) levels. We calculated pre-treatment LDL levels utilizing prior published literature by adjusting for serum LDL levels in patients receiving statins. This increased the diagnostic yield for gene-positive FH. Hypothesis: Integration of statin-correction calculator with the Dutch Lipid Clinical Criteria (DLCC) and Simon Broome Criteria (SBC) for FH will increase sensitivity to identify gene-positive FH. Methods: 29,797 participants enrolled in the Healthy Nevada Project underwent whole-exome gene testing. 126 had a FH variant; 37 of these participants were on statin therapy. A statin-correction calculator was utilized to predict patients' pre-treatment LDL levels. The likelihood of FH was assessed based on two versions of the DLCC and SBC: the standard versions and enhanced versions with integration of the statin-correction calculator (eDLCC and eSBC). The McNemar test was used to compare the sensitivity of DLCC and SBC with eDLCC and eSBC, respectively, in identifying gene-positive FH. Results: By adjusting LDL levels for statin usage, 70.24% and 24.32% of participants with a negative diagnosis of FH were reclassified to positive using eDLCC and eSBC (p=0.001 and 0.008, respectively). Conclusions: Integration of statin-correction calculator to correct LDL increases diagnostic yield for clinical FH.

scholarly journals Long-term use of a combination of atorvastatin and ezetimibe in children with homozygous familial hypercholesterolemia

2017 ◽  
Vol 5 (1) ◽  
pp. 275
Author(s):  
Devi Dayal ◽  
Keerthivasan Seetharaman ◽  
Savita Bhunwal ◽  
Nimisha Jain
Keyword(s):  
Familial Hypercholesterolemia ◽  
Genetic Disorder ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Homozygous Familial Hypercholesterolemia ◽  
Limited Data ◽  
Low Density Lipoprotein Cholesterol

Background: Homozygous familial hypercholesterolemia (HoFH) is an underdiagnosed and undertreated genetic disorder of lipoprotein metabolism associated with mortality during young age due to accelerated atherosclerosis. There is limited data on the efficacy of lipid lowering therapies in HoFH. Methods: Medical records of 3 children with HoFH who received a combination of atorvastatin and ezetimibe for a mean duration of 11.6±1.5 years were retrospectively analysed. Results: There was a significant decrease in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) from the baseline levels (mean percent change in TC, LDL-C, TG and HDL-C of 58.5%, 56.2%, 67.5% and 29.7% respectively). Conclusions: We conclude that long-term use of a combination of atorvastatin and ezetimibe significantly lowers the plasma LDL-C concentrations in patients with HoFH without causing any significant adverse effects. Ours is the first study from India on long-term use of lipid modifying drug therapy in children with HoFH.

Clinical implications and outcomes of the ORION Phase III trials

2020 ◽  
Author(s):  
Julia Brandts ◽  
Kausik K Ray
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Phase Iii ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density Lipoprotein Cholesterol ◽  
Clinical Safety ◽  
Phase Iii Trials ◽  
Phase Ii And Iii ◽  
Ongoing Phase

Inclisiran is a siRNA inhibiting hepatic PCSK9 synthesis. As a first-in-class therapy, inclisiran has been assessed within the ORION trial program for its low-density lipoprotein cholesterol (LDL-C) lowering efficacy and clinical safety. Phase II and III trials have shown that inclisiran lowers LDL-C by about 50% with an infrequent dosing schedule in patients with established atherosclerotic cardiovascular disease and those at high risk, including patients with heterozygous familial hypercholesterolemia. Ongoing Phase III trials will provide evidence on longer-term safety and effectiveness, and inclisiran’s efficacy in patients with homozygous familial hypercholesterolemia. Furthermore, the ORION-4 trial will assess inclisiran’s impact on cardiovascular outcomes.

scholarly journals Preliminary Results of CitraVes™ Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot Open-Label Study

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 276
Author(s):  
Stefania Raimondo ◽  
Dragana Nikolic ◽  
Alice Conigliaro ◽  
Gianluca Giavaresi ◽  
Bruna Lo Sasso ◽  
...  
Keyword(s):  
Risk Factors ◽  
Healthy Subjects ◽  
Cardiometabolic Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Modifiable Risk Factors ◽  
Low Density Lipoprotein Cholesterol ◽  
Open Label ◽  
Open Label Study ◽  
Label Study

Appropriate monitoring and control of modifiable risk factors, such as the level of low-density lipoprotein cholesterol (LDL-C) and other types of dyslipidemia, have an important role in the prevention of cardiovascular diseases (CVD). Recently, various nutraceuticals with lipid-lowering effects have gained attention. In addition to the plant-derived bioactive compounds, recent studies suggested that plant cells are able to release small lipoproteic structures named extracellular vesicles (EVs). The interaction between EVs and mammalian cells could lead to beneficial effects through anti-inflammatory and antioxidant activities. The present study aimed to assess the safety of the new patented plant-based product citraVes™, containing extracellular vesicles (EVs) from Citrus limon (L.) Osbeck juice, and to investigate its ability to modulate different CV risk factors in healthy subjects. A cohort of 20 healthy volunteers was recruited in a prospective open-label study. All participants received the supplement in a spray-dried formulation at a stable dose of 1000 mg/day for 3 months. Anthropometric and hematobiochemical parameters were analyzed at the baseline and after the follow-up period of 1 and 3 months. We observed that the supplement has an effect on two key factors of cardiometabolic risk in healthy subjects. A significant change in waist circumference was found in women after 4 (85.4 [79.9, 91.0] cm, p < 0.005) and 12 (85.0 [80.0, 90.0] cm, p < 0.0005) weeks, when compared to the baseline value (87.6 [81.7, 93.6] cm). No difference was found in men (baseline: 100.3 [95.4, 105.2] cm; 4 weeks: 102.0 [95.7, 108.3] cm; 12 weeks: 100.0 [95.3, 104.7] cm). The level of LDL-C was significantly lower at 12 weeks versus 4 weeks (p = 0.0064). Our study evaluated, for the first time, the effects of a natural product containing plant-derived EVs on modifiable risk factors in healthy volunteers. The results support the use of EV extracts to manage cardiometabolic risk factors successfully.

scholarly journals The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 66
Author(s):  
Alexey Meshkov ◽  
Alexandra Ershova ◽  
Anna Kiseleva ◽  
Evgenia Zotova ◽  
Evgeniia Sotnikova ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Significant Proportion ◽  
Density Lipoprotein ◽  
Genetic Diagnostics ◽  
Atherosclerotic Cardiovascular Disease ◽  
Gene Variants ◽  
Systematic Analysis ◽  
Pcsk9 Gene ◽  
Cholesterol Levels

Familial hypercholesterolemia (FH) is a common autosomal codominant disorder, characterized by elevated low-density lipoprotein cholesterol levels causing premature atherosclerotic cardiovascular disease. About 2900 variants of LDLR, APOB, and PCSK9 genes potentially associated with FH have been described earlier. Nevertheless, the genetics of FH in a Russian population is poorly understood. The aim of this study is to present data on the spectrum of LDLR, APOB, and PCSK9 gene variants in a cohort of 595 index Russian patients with FH, as well as an additional systematic analysis of the literature for the period of 1995–2020 on LDLR, APOB and PCSK9 gene variants described in Russian patients with FH. We used targeted and whole genome sequencing to search for variants. Accordingly, when combining our novel data and the data of a systematic literature review, we described 224 variants: 187 variants in LDLR, 14 variants in APOB, and 23 variants in PCSK9. A significant proportion of variants, 81 of 224 (36.1%), were not described earlier in FH patients in other populations and may be specific for Russia. Thus, this study significantly supplements knowledge about the spectrum of variants causing FH in Russia and may contribute to a wider implementation of genetic diagnostics in FH patients in Russia.

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