scholarly journals MicroRNA-33b is a Potential Non-Invasive Biomarker for Response to Atorvastatin Treatment in Chilean Subjects With Hypercholesterolemia: A Pilot Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Carmen Gloria Ubilla ◽  
Yalena Prado ◽  
Jeremy Angulo ◽  
Ignacio Obreque ◽  
Isis Paez ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Statin Treatment ◽  
Lipid Lowering ◽  
Atorvastatin Treatment ◽  
Non Invasive ◽  
Before And After ◽  
Atorvastatin Therapy ◽  
Extracellular Mirnas ◽  
Lowering Drug ◽  
Mirnas Expression

Evidence accumulated so far indicates that circulating levels of microRNAs (miRNAs) are associated with several pathologies. Therefore, differential expression of extracellular miRNAs exhibits promising potential for screening and diagnosis purposes. We evaluated plasma miRNAs in response to the lipid-lowering drug atorvastatin in patients with hypercholesterolemia (HC) and controls. Methods: We selected miRNAs based on previous data reported by our group and also by employing bioinformatics tools to identify 10 miRNAs related to cholesterol metabolism and statin response genes. Following miRNA identification, we determined plasma levels of miRNA-17-5p, miRNA-30c-5p, miRNA-24-3p, miRNA-33a-5p, miRNA-33b-5p, miRNA-29a-3p, miRNA-29b-3p, miRNA-454-3p, miRNA-590-3p and miRNA-27a-3p in 20 HC patients before and after 1 month of 20 mg/day atorvastatin treatment, evaluating the same miRNA set in a group of 20 healthy subjects, and employing qRT-PCR to determine differential miRNAs expression. Results: HC individuals showed significant overexpression of miRNA-30c-5p and miRNA-29b-3p vs. NL (p = 0.0008 and p = 0.0001, respectively). Once cholesterol-lowering treatment was concluded, HC individuals showed a substantial increase of three extracellular miRNAs (miRNA-24-3p, miRNA-590, and miRNA-33b-5p), the latter elevated more than 37-fold (p = 0.0082). Conclusion: Data suggest that circulating miRNA-30c-5p and miRNA-29b-3p are associated with hypercholesterolemia. Also, atorvastatin induces a strong elevation of miRNA-33b-5p levels in HC individuals, which could indicate an important function that this miRNA may exert upon atorvastatin therapy. Additional studies are needed to clarify the role of this particular miRNA in statin treatment.

scholarly journals Atorvastatin Increases the Expression of Long Non-Coding RNAs ARSR and CHROME in Hypercholesterolemic Patients: A Pilot Study

2020 ◽  
Vol 13 (11) ◽  
pp. 382
Author(s):  
Isis Paez ◽  
Yalena Prado ◽  
Carmen G. Ubilla ◽  
Tomás Zambrano ◽  
Luis A. Salazar
Keyword(s):  
Lipid Profile ◽  
Cholesterol Metabolism ◽  
Cholesterol Homeostasis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Single Nucleotide ◽  
Additional Information ◽  
Before And After ◽  
Non Coding Rnas ◽  
Statin Response

Atorvastatin is extensively used to treat hypercholesterolemia. However, the wide interindividual variability observed in response to this drug still needs further elucidation. Nowadays, the biology of long non-coding RNAs (lncRNAs) is better understood, and some of these molecules have been related to cholesterol metabolism. Therefore, they could provide additional information on variability in response to statins. The objective of this research was to evaluate the effect of atorvastatin on three lncRNAs (lncRNA ARSR: Activated in renal cell carcinoma (RCC) with sunitinib resistance, ENST00000424980; lncRNA LASER: lipid associated single nucleotide polymorphism locus, ENSG00000237937; and lncRNA CHROME: cholesterol homeostasis regulator of miRNA expression, ENSG00000223960) associated with genes involved in cholesterol metabolism as predictors of lipid-lowering therapy performance. Twenty hypercholesterolemic patients were treated for four weeks with atorvastatin (20 mg/day). The lipid profile was determined before and after drug administration using conventional assays. The expression of lncRNAs was assessed in peripheral blood samples by RT-qPCR. As expected, atorvastatin improved the lipid profile, decreasing total cholesterol, LDL-C, and the TC/HDL-C ratio (p < 0.0001) while increasing the expression of lncRNAs ARSR and CHROME (p < 0.0001) upon completion of treatment. LASER did not show significant differences among the groups (p = 0.50). Our results indicate that atorvastatin modulates the expression of cholesterol-related lncRNAs differentially, suggesting that these molecules play a role in the variability of response to this drug; however, additional studies are needed to disclose the implication of this differential regulation on statin response.

scholarly journals Pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitus

2016 ◽  
Vol 19 (3) ◽  
pp. 204-211
Author(s):  
Nadezhda O. Lebedeva ◽  
Olga K. Vikulova ◽  
Alexei G. Nikitin ◽  
Minara Sh. Shamkhalova ◽  
Marina V. Shestakova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Function ◽  
Statin Therapy ◽  
Lipid Lowering ◽  
Before And After ◽  
Atorvastatin Therapy

Aim. To investigate the association of variation in lipid-lowering response and endothelial function (EF) parameters after atorvastatin therapy in patients with type 2 diabetes mellitus (T2DM) with genetic markers of atherosclerosis.Methods. We included 97 patients with T2DM who were prescribed atorvastatin. Fasting lipid profiles and EF parameters were assessed before and after 12 months of statin therapy. For EF evaluation, we performed pulse-wave analysis during reactive hyperaemia. The genotypes for polymorphic markers were identified by real-time polymerase chain reaction with TaqMan probes. The statistical analysis included Wilcoxon, Mann–Whitney and Kruskal–Wallis tests. P-values 0.05 were considered statistically significant.Results. With statin therapy, PPARG2Pro/Pro patients had significantly lower TC and LDL-C levels than PPARG2 Pro/Ala and PPARG2 Ala/Ala patients (TC: 20.74% vs. 4.6% and 5.61%; p = 0.04 and LDL-C: 26.00% vs. 6.11% and 7.32%; p = 0.029). Patients with АРОЕЕ4/Е4 had significantly lower TC and TG levels than other АРОЕ patients (TC: -46.25% for Е4/Е4 vs. +33.33% for Е4/Е2, +5.73% for Е3/Е2, +11.80% for Е3/Е4, -10.92% for Е3/Е3, р = 0,01; TG: -56.52% for Е4/Е4 vs. +24.43% for Е4/Е2, +19.63% for Е3/Е2, +8.05% for Е3/Е4, -20.00% for Е3/Е3, р = 0.04). The patients with GG for TNFα G(238)A and GA for TNFα G(308)A had significantly greater amplitude of post-occlusive wave increase (Apw) than patients with GA for TNFα G(238)A and GG for TNFα G(308)A (+8.16 % vs. -0.93%, р = 0,04; +44% vs. -4.4%, p = 0.004, respectively).Conclusion. PPARG2Pro12Ala and АРОЕE2/Е3/Е4 polymorphism contributed to the between-patient variability in the response to statin therapy in patients with T2DM. Significant associations of the TNFαgene polymorphism with EF in patients with T2DM suggest an important role of inflammation in the pathogenesis of MVD.

Berberine: A Promising Natural Isoquinoline Alkaloid for the Development of Hypolipidemic Drugs

2020 ◽  
Vol 20 (28) ◽  
pp. 2634-2647
Author(s):  
Dong-Dong Li ◽  
Pan Yu ◽  
Wei Xiao ◽  
Zhen-Zhong Wang ◽  
Lin-Guo Zhao
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Physicochemical Properties ◽  
Isoquinoline Alkaloid ◽  
Hypolipidemic Activity ◽  
Lipid Lowering ◽  
Lipid Lowering Drug ◽  
Lipid Lowering Agent ◽  
Lowering Drug ◽  
Hypolipidemic Drugs

: Berberine, as a representative isoquinoline alkaloid, exhibits significant hypolipidemic activity in both animal models and clinical trials. Recently, a large number of studies on the lipid-lowering mechanism of berberine and studies for improving its hypolipidemic activity have been reported, but for the most part, they have been either incomplete or not comprehensive. In addition, there have been a few specific reviews on the lipid-reducing effect of berberine. In this paper, the physicochemical properties, the lipid-lowering mechanism, and studies of the modification of berberine all are discussed to promote the development of berberine as a lipid-lowering agent. Subsequently, this paper provides some insights into the deficiencies of berberine in the study of lipid-lowering drug, and based on the situation, some proposals are put forward.

Efficacy and Safety of Evolocumab in Reducing Low Density Lipoprotein Cholesterol Levels in Chinese Patients with Non-ST-segment Elevation Acute Coronary Syndrome

2020 ◽  
Vol 18 ◽  
Author(s):  
Xiaohan Xu ◽  
Meng Chai ◽  
Yujing Cheng ◽  
Pingan Peng ◽  
Xiaoli Liu ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Chinese Patients ◽  
Lipid Lowering ◽  
Control Group ◽  
Lipid Lowering Therapy ◽  
St Segment Elevation ◽  
Coronary Syndrome ◽  
St Segment

Aims: To explore early intensive lipid-lowering therapy in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Background: Lowering low-density lipoprotein cholesterol (LDL-C) levels can reduce cardiovascular morbidity and mortality in patients with atherosclerotic cardiovascular disease. Due to many reasons, the need for early intensive lipid-lowering therapy is far from being met in Chinese NSTE-ACS patients at high-risk of recurrent ischaemic events. Objective: To evaluate the feasibility, safety and efficacy of starting evolocumab in hospital to lower LDL-C levels in Chinese patients with NSTE-ACS. Methods: In this prospective cohort study initiated by researchers, 334 consecutive patients with NSTE-ACS who had sub-standard LDL-C levels (LDL-C ≥2.3 mmol/L after regular oral statin treatment for at least 4 weeks; or LDL-C ≥3.2 mmol/L without regular oral statin treatment) were included. Patients who agreed to treatment with evolocumab (140 mg subcutaneously every 2 weeks, initiated in hospital and used for 12 weeks after discharge) were enrolled in the evolocumab group (n=96) and others in the control group (n=238). All enrolled patients received regular statin treatment (atorvastatin 20 mg/day or rosuvastatin 10 mg/day; doses unchanged throughout the study).The primary endpoint was the change in LDL-C levels from baseline to week 12. Results: Most patients (67.1%) had not received regular statin treatment before. In the evolocumab group, LDL-C levels decreased significantly at week 4 and remained stable at week 8 and 12 (all p<0.001). At week 12, the LDL-C percentage change from baseline in the evolocumab group was -79.2±12.7% (from an average of 3.7 to 0.7 mmol/L), while in the control group it was -37.4±15.4% (from an average of 3.3 to 2.0 mmol/L). The mean difference between these 2 groups was -41.8% (95% CI -45.0 to -38.5%; p<0.001). At week 12, the proportions of patients with LDL-C levels <1.8 mmol/L and 1.4 mmol/L in the evolocumab group were significantly higher than in the control group (96.8 vs 36.1%; 90.6 vs 7.1%; both p<0.001). The incidence of adverse events and cardiovascular events was similar in both groups. Conclusions: In this prospective cohort study we evaluated the early initiation of evolocumab in NSTE-ACS patients in China. Evolocumab combined with statins significantly lowered LDL-C levels and increased the probability of achieving recommended LDL-C levels, with satisfactory safety and well tolerance.

scholarly journals Cerebellar rTMS in PSP: a Double-Blind Sham-Controlled Study Using Mobile Health Technology

2021 ◽  
Author(s):  
Andrea Pilotto ◽  
Maria Cristina Rizzetti ◽  
Alberto Lombardi ◽  
Clint Hansen ◽  
Michele Biggi ◽  
...  
Keyword(s):  
Digital Technology ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Health Technology ◽  
Controlled Study ◽  
Double Blind ◽  
Non Invasive ◽  
Lower Back ◽  
Before And After ◽  
Double Blind Design ◽  
Theta Burst

AbstractThere are no effective treatments in progressive supranuclear palsy (PSP). The aim of this study was to test the efficacy of theta burst repetitive transcranial magnetic stimulation (rTMS) on postural instability in PSP. Twenty PSP patients underwent a session of sham or real cerebellar rTMS in a crossover design. Before and after stimulation, static balance was evaluated with instrumented (lower back accelerometer, Rehagait®, Hasomed, Germany) 30-s trials in semitandem and tandem positions. In tandem and semitandem tasks, active stimulation was associated with increase in time without falls (both p=0.04). In the same tasks, device-extracted parameters revealed significant improvement in area (p=0.007), velocity (p=0.005), acceleration and jerkiness of sway (p=0.008) in real versus sham stimulation. Cerebellar rTMS showed a significant effect on stability in PSP patients, when assessed with mobile digital technology, in a double-blind design. These results should motivate larger and longer trials using non-invasive brain stimulation for PSP patients.

How many CCS- and ACS-patients might reach the newly recommended LDL-C-target <55mg/dl in clinical practice if guidelines were applied – an estimate from the DYSIS II study population

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A.K Gitt ◽  
M Horack ◽  
D Lautsch ◽  
R Zahn ◽  
J Ferrieres
Keyword(s):  
Clinical Practice ◽  
Real Life ◽  
Statin Treatment ◽  
Lipid Lowering ◽  
High Risk Population ◽  
High Dose ◽  
Funding Source ◽  
Pcsk9 Inhibitors ◽  
Target Values ◽  
Coronary Syndromes

Abstract Background The 2019 ESC guidelines for the management of dyslipidemia even further lowered the LDL-C-target values for the very high-risk population from &lt;70mg/dl to &lt;55mg/dl. Population based studies already had shown that the previous target was difficult to reach. It is yet unclear how many patients in clinical practice might be treated to the new target. Methods The Dyslipidemia International Study (DYSIS II) prospectively collected data of patients with chronic coronary syndromes (CCS) and acute coronary syndromes (ACS) (all on statins) in 18 countries in Europe, the Middle East, South- and East Asia to document patient characteristics, medication and a current lipid profile from 2012 to 2014 under real life conditions in physicians' offices and hospitals. We took these real-life lipid profiles and data on the kind/dose of used statins to estimate how treatment escalation such as changing statin treatment to a high dose (atorvastatin ≥40mg / rosuvastatin≥20mg), adding ezetimibe and adding a PCSK9-inhibitor might help to bring LDL-C-levels to the recommended &lt;55mg/dl target. Results A total of 7,865 patients were enrolled into DYSIS II, 6,794 had CCS and 1,071 ACS. Under the documented statin treatment in DYSIS only 12.7% of patients reached an LDL-C &lt;55mg/dl. Putting all patients on high dose statins in combination with ezetimibe, 64.1% would reach the target. If PCSK9-inhibitors would be used in the remaining patients not at goal a total of 94.0% would match the goal. Conclusion Our analysis indicates that in real life practice the use available lipid-lowering medications would substantially increase the percentage of CCS- and ACS-patients reaching the newly recommended 2019 ESC guideline LDL-C-target of &lt;55 mg/dl from less than 20% to more than 90% of the population. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): MSD

scholarly journals Coronary lesion complexity in patients with heterozygous familial hypercholesterolemia hospitalized for acute myocardial infarction: data from the RICO survey

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Hermann Yao ◽  
Michel Farnier ◽  
Laura Tribouillard ◽  
Frédéric Chague ◽  
Philippe Brunel ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Ldl Cholesterol ◽  
Statin Treatment ◽  
Lipid Lowering ◽  
Syntax Score ◽  
Lipid Lowering Therapy ◽  
Lipid Clinic ◽  
Acute Mi ◽  
Artery Disease

Abstract Background Although patients with familial heterozygous hypercholesterolemia (FH) have a high risk of early myocardial infarction (MI), the coronary artery disease (CAD) burden in FH patients with acute MI remains to be investigated. Methods The data for all consecutive patients hospitalized in 2012–2019 for an acute MI and who underwent coronary angiography were collected from a multicenter database (RICO database). FH (n = 120) was diagnosed using Dutch Lipid Clinic Network criteria (score ≥ 6). We compared the angiographic features of MI patients with and without FH (score 0–2) (n = 234) after matching for age, sex, and diabetes (1:2). Results Although LDL-cholesterol was high (208 [174–239] mg/dl), less than half of FH patients had chronic statin treatment. When compared with non-FH patients, FH increased the extent of CAD (as assessed by SYNTAX score; P = 0.005), and was associated with more frequent multivessel disease (P = 0.004), multiple complex lesions (P = 0.022) and significant stenosis location on left circumflex and right coronary arteries. Moreover, FH patients had more multiple lesions, with an increased rate of bifurcation lesions or calcifications (P = 0.021 and P = 0.036, respectively). In multivariate analysis, LDL-cholesterol levels (OR 1.948; 95% CI 1.090–3.480, P = 0.024) remained an independent estimator of anatomical complexity of coronary lesions, in addition to age (OR 1.035; 95% CI 1.014–1.057, P = 0.001). Conclusions FH patients with acute MI had more severe CAD, characterized by complex anatomical features that are mainly dependent on the LDL-cholesterol burden. Our findings reinforce the need for more aggressive preventive strategies in these high-risk patients, and for intensive lipid-lowering therapy as secondary prevention.

scholarly journals CT perfusion in peripheral arterial disease—hemodynamic differences before and after revascularisation

2021 ◽  
Author(s):  
Patrick Veit-Haibach ◽  
Martin W. Huellner ◽  
Martin Banyai ◽  
Sebastian Mafeld ◽  
Johannes Heverhagen ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Ct Perfusion ◽  
Arterial Disease ◽  
Lower Leg ◽  
Therapy Control ◽  
Non Invasive ◽  
Before And After ◽  
Invasive Method ◽  
The Mean ◽  
Peripheral Arterial

Abstract Objectives The purpose of this study was the assessment of volumetric CT perfusion (CTP) of the lower leg musculature in patients with symptomatic peripheral arterial disease (PAD) before and after interventional revascularisation. Methods Twenty-nine consecutive patients with symptomatic PAD of the lower extremities requiring interventional revascularisation were assessed prospectively. All patients underwent a CTP scan of the lower leg, and hemodynamic and angiographic assessment, before and after intervention. Ankle-brachial pressure index (ABI) was determined. CTP parameters were calculated with a perfusion software, acting on a no outflow assumption. A sequential two-compartment model was used. Differences in CTP parameters were assessed with non-parametric tests. Results The cohort consisted of 24 subjects with an occlusion, and five with a high-grade stenosis. The mean blood flow before/after (BFpre and BFpost, respectively) was 7.42 ± 2.66 and 10.95 ± 6.64 ml/100 ml*min−1. The mean blood volume before/after (BVpre and BVpost, respectively) was 0.71 ± 0.35 and 1.25 ± 1.07 ml/100 ml. BFpost and BVpost were significantly higher than BFpre and BVpre in the treated limb (p = 0.003 and 0.02, respectively), but not in the untreated limb (p = 0.641 and 0.719, respectively). Conclusions CTP seems feasible for assessing hemodynamic differences in calf muscles before and after revascularisation in patients with symptomatic PAD. We could show that CTP parameters BF and BV are significantly increased after revascularisation of the symptomatic limb. In the future, this quantitative method might serve as a non-invasive method for surveillance and therapy control of patients with peripheral arterial disease. Key Points • CTP imaging of the lower limb in patients with symptomatic PAD seems feasible for assessing hemodynamic differences before and after revascularisation in PAD patients. • This quantitative method might serve as a non-invasive method, for surveillance and therapy control of patients with PAD.

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