Treatment Of Dyslipidemia In Patients Research Articles

High-salt diet induces dyslipidemia through the SREBP2/PCSK9 pathway in dahl salt-sensitive rats

A high-salt diet is known to increase serum cholesterol levels; however, the underlying mechanism of salt-induced dyslipidemia in patients with salt-sensitivity remains poorly understood. We aimed to investigate whether high-salt diet (HSD) can induce dyslipidemia and elucidate the underlying mechanism of salt-induced dyslipidemia in Dahl salt-sensitive (SS) rats. Metabolomic and biochemical analyses revealed that the consumption of an HSD (8 % NaCl) significantly increased the serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in SS rats. The enzyme-linked immunosorbent assay demonstrated an increase in circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels, accompanied by a decrease in hepatic low-density lipoprotein receptor (LDLR) levels due to HSD consumption. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis revealed that HSD consumption activated sterol regulatory element-binding protein-2 (SREBP2) expression in the liver and kidney, resulting in upregulation of PCSK9 at the transcriptional level in the liver and at the translational level in the kidney, ultimately increasing circulating PCSK9 levels. The combined effects of HSD on the liver and kidney contributed to the development of hypercholesterolemia. Furthermore, an in vitro assay confirmed that high-salt exposure led to an increase in the protein expression of SREBP2 and PCSK9 secretion, thereby reducing low-density lipoprotein (LDL) uptake. This study, for the first time, shows that an HSD induces dyslipidemia through activation of the SREBP2/PCSK9 pathway, providing new insights into the prevention and treatment of dyslipidemia in patients with salt sensitivity.

#4791 TREATMENT WITH PCSK9 INHIBITORS IN PATIENTS WITH CHRONIC KIDNEY DISEASE AT VERY HIGH CARDIOVASCULAR RISK

Abstract Background and Aims Proprotein convertase subtilisin/kexin type 9 (iPCSK9) inhibitors may be an option in the treatment of dyslipidaemia in patients with chronic kidney disease (CKD) who do not reach therapeutic targets or who do not tolerate statins at maximal doses. However, studies in this population are scarce. The aim of our study is to analyse the efficacy and safety of iPCSK9 in patients with CKD. Method Retrospective cohort study of patients with CKD, defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, who started treatment with iPCSK9 in our centre between 2016 and 2020. All patients had at least 2 years of follow-up. We compared total cholesterol, LDL cholesterol (c-LDL), triglycerides and eGFR at baseline, 6, 12 and 24 months after iPCSK9 prescription. Adverse effects were collected. Results During the study period, 278 patients started treatment with iPCSK9 in our centre, of whom 41 had CKD and a follow-up of more than 2 years. Of these, 21 were on treatment with Alirocumab and 20 with Evolocumab. Of these, 51.2% were men with a mean age of 70.6 ± 9.4 years and 87.8% had G3a or G3b stage. One patient was on peritoneal dialysis. Acquired dyslipidaemia was present in 82.9% and 87.8% had suffered from coronary events. 53.7% of iPCSK9 prescriptions were for failure to achieve c-LDL targets, while in the remaining patients the reason was non-tolerance of maximum statin doses. After 6 months of treatment, a significant reduction in total cholesterol (226.7 ± 52.9 mg/dL vs. 142.1 ± 46.17 mg/dL; p<0.001), c-LDL (147.8 ± 48.8 mg/dL vs. 62.9 ± 37.1 mg/dL; p<0.001) and triglycerides (229.8 ± 112.4 mg/dL vs. 192.4 ± 119.2 mg/dL; p = 0.025) was observed, and these differences were maintained at 2 years of treatment (p = 0.016, p<0.001, p = 0.004). 48.8% of patients achieved c-LDL targets (≤ 55 mg/dL) at 6 months of treatment and 48.8% at 12 months of treatment. Renal function remained stable during follow-up. No side effects or cardiovascular events were documented. Conclusion iPCSK9 reduce cholesterol, c-LDL and triglycerides in patients with CKD, allowing therapeutic targets to be achieved while maintaining stable renal function. Due to the apparent advantages of this drug in CKD patients, we believe that conducted clinical trials should be designed for this population.

The appropriateness of the use of statins for the secondary and primary prevention of atherosclerotic cardiovascular disease: a cross-sectional study from Jordan.

The appropriate use of statins to lower blood cholesterol remains the main strategy for primary and secondary prevention of atherosclerotic cardiovascular diseases (ASCVD). Here, we aim to examine the pattern of statin use and the appropriateness of dyslipidemia treatment in patients with or without established ASCVD according to the latest American Heart Association/American College of Cardiology (AHA/ACC) guidelines. This is a cross-sectional study conducted in the largest tertiary government hospital in Jordan. Data was collected through face-to-face interviews and the review of medical records. A total of 752 patients were enrolled, 740 (98.4%) patients were on atorvastatin, 8 (1.1%) were on simvastatin, 3 (0.4%) were on rosuvastatin, and 1 (0.1%) was on fluvastatin. The majority of patients, 550 (73.1%), used statins for secondary prevention. Only half of the patients, 367 (49.7%), received statin treatment at the intensity recommended by the guidelines. A large percentage of patients, 306 (40.7%), were undertreated with statins, and the management of dyslipidemia was not accompanied by appropriate follow-up. Based on the latest guidelines' recommendations, older age (p = 0.027), longer duration of statin use (p = 0.005), increased number of ASCVDs (p < 0.001), using statins other than atorvastatin (p = 0.004), and a history of angina (p < 0.001) or stroke (p < 0.001) were associated with undertreatment with statins. The use of statins was not in concordance with the guidelines. Many of the patients surveyed were undertreated and adequate follow-up to identify the extent of patients' compliance and response was missing.

Effect of polymorphisms in drug metabolism and transportation on plasma concentration of atorvastatin and its metabolites in patients with chronic kidney disease.

Dyslipidemia due to renal insufficiency is a common complication in patients with chronic kidney diseases (CKD), and a major risk factor for the development of cardiovascular events. Atorvastatin (AT) is mainly used in the treatment of dyslipidemia in patients with CKD. However, response to the atorvastatin varies inter-individually in clinical applications. We examined the association between polymorphisms in genes involved in drug metabolism and transport, and plasma concentrations of atorvastatin and its metabolites (2-hydroxy atorvastatin (2-AT), 2-hydroxy atorvastatin lactone (2-ATL), 4-hydroxy atorvastatin (4-AT), 4-hydroxy atorvastatin lactone (4-ATL), atorvastatin lactone (ATL)) in kidney diseases patients. Genotypes were determined using TaqMan real time PCR in 212 CKD patients, treated with 20mg of atorvastatin daily for 6weeks. The steady state plasma concentrations of atorvastatin and its metabolites were quantified using ultraperformance liquid chromatography in combination with triple quadrupole mass spectrometry (UPLC-MS/MS). Univariate and multivariate analyses showed the variant in ABCC4 (rs3742106) was associated with decreased concentrations of AT and its metabolites (2-AT+2-ATL: β = -0.162, p = 0.028 in the dominant model; AT+2-AT+4-AT: β = -0.212, p = 0.028 in the genotype model), while patients carrying the variant allele ABCC4-rs868853 (β = 0.177, p = 0.011) or NR1I2-rs6785049 (β = 0.123, p = 0.044) had higher concentrations of 2-AT+2-ATL in plasma compared with homozygous wildtype carriers. Luciferase activity was enhanced in HepG2 cells harboring a construct expressing the rs3742106-T allele or the rs868853-G allele (p < 0.05 for each) compared with a construct expressing the rs3742106G or the rs868853-A allele. These findings suggest that two functional polymorphisms in the ABCC4 gene may affect transcriptional activity, thereby directly or indirectly affecting release of AT and its metabolites from hepatocytes into the circulation.

Real world efficacy of bempedoic acid in statin-intolerant patients with high cardiovascular risk

Background and Aims: Bempedoic acid (an ATP citrate lyase inhibitor) has recently been licensed for the treatment of dyslipidaemia in patients who are intolerant of statins. We aimed to assess if the tolerability and efficacy seen in clinical trials could be replicated in statin-intolerant patients in routine clinical practice.

EE285 Cost-Effectiveness of Evolocumab Versus Standard Therapy for the Treatment of Dyslipidemia in Patients with Cardiovascular Disease in Qatar

The study aimed to evaluate the cost-effectiveness of evolocumab in combination with high-intensity or moderate-intensity statin therapy compared to standard therapy (i.e., statin therapy alone) for the treatment of dyslipidemia in patients with atherosclerotic cardiovascular disease in Qatar.

Pairing 3D-Printing with Nanotechnology to Manage Metabolic Syndrome.

IntroductionThis work was aimed to develop a Curcuma oil-based self-nanoemulsifying drug delivery system (SNEDDS) 3D-printed polypills containing glimepiride (GMD) and rosuvastatin (RSV) for treatment of dyslipidemia in patients with diabetes as a model for metabolic syndrome (MS).MethodsCompartmentalized 3D printed polypills were prepared and studied in streptozotocin/poloxamer induced diabetic/dyslipidemic rats. The pharmacokinetic parameters of GMD and RSV in the prepared polypills were evaluated. Blood glucose level, lipid profile, antioxidant, and biochemical markers activities were investigated. Also, histopathological examination of the liver and pancreas was carried out. The atherosclerotic index, the area of islets of Langerhans, and liver steatosis lesion scores were calculated.ResultsThe developed SNEDDS-loaded GMD/RSV polypills showed acceptable quality control characteristics with a high relative bioavailability of 217.16% and 224.28% for GMD and RSV, respectively, when compared with the corresponding non-SNEDDS pills. The prepared polypills showed dramatic lowering in blood glucose levels and substantial improvement in lipid profile and hepatic serum biomarkers as well as remarkable decrease in serum antioxidants in response to Poloxamer 407 intoxication. The prepared polypills decreased the risk of atherosclerosis and coronary disease by boosting the level of high-density lipoprotein and lowering both triglyceride and low-density lipoprotein. Microscopic examination showed normal hepatic sinusoids and high protection level with less detectable steatosis in the examined hepatocytes. Normal size pancreatic islets with apparently normal exocrine acini and pancreatic duct were also noticed.ConclusionThis formulation strategy clearly shows the potential of the developed polypills in personalized medicine for treatment of patients with MS.

A retrospective analysis of the experimental and clinical study of pasenin, a drug for the treatment of dyslipidemia in patients with diabetes mellitus

A retrospective analysis of the experimental and clinical study of pasenin, a drug for the treatment of dyslipidemia in patients with diabetes mellitus

Comparison of Efficacy and Safety of Statin-Ezetimibe Combination Therapy with Statin Monotherapy in Patients with Diabetes: A Meta-Analysis of Randomized Controlled Studies.

Dyslipidemia in diabetes mellitus is characterized by hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and elevated low-density lipoprotein cholesterol (LDL-C). Additionally, the potentially increased risk of morbidity and mortality following atherosclerotic cardiovascular diseases should be considered in the treatment of dyslipidemia in patients with diabetes. We performed a meta-analysis of the published data to compare the effects of HMG-CoA reductase inhibitor (statin)-ezetimibe combination therapy and statin monotherapy on lipid and glucose parameters in patients with diabetes. We also compared safety based on the adverse events reported for the two groups. In total, 17 articles were included in this meta-analysis. In the efficacy assessment, the combination treatment afforded a significantly greater reduction in LDL-C than did statin monotherapy (standard difference in means 0.691; 95% confidence interval 0.534-0.847). A significantly greater improvement effect was observed in the levels of HDL-C, total cholesterol, triglyceride, and apolipoprotein B, but not apolipoprotein A1, with combination therapy than with statin monotherapy. Additionally, combination therapy reduced fasting blood glucose levels more significantly than did statin monotherapy. In terms of safety, there were no significant differences in treatment-related adverse events between the two treatments. Statin-ezetimibe combination therapy enhances levels of LDL-C and other lipids without increasing the risk of adverse events compared with statin monotherapy. The present meta-analysis presents valid evidence for appropriate drug regimens to treat dyslipidemia in patients with diabetes. PROSPERO Identifier Number CRD42021244578.

Development of Multi-Compartment 3D-Printed Tablets Loaded with Self-Nanoemulsified Formulations of Various Drugs: A New Strategy for Personalized Medicine.

This work aimed to develop a three-dimensional printed (3DP) tablet containing glimepiride (GLMP) and/or rosuvastatin (RSV) for treatment of dyslipidemia in patients with diabetes. Curcumin oil was extracted from the dried rhizomes of Curcuma longa and utilized to develop a self-nanoemulsifying drug delivery system (SNEDDS). Screening mixture experimental design was conducted to develop SNEDDS formulation with a minimum droplet size. Five different semi-solid pastes were prepared and rheologically characterized. The prepared pastes were used to develop 3DP tablets using extrusion printing. The quality attributes of the 3DP tablets were evaluated. A non-compartmental extravascular pharmacokinetic model was implemented to investigate the in vivo behavior of the prepared tablets and the studied marketed products. The optimized SNEDDS, of a 94.43 ± 3.55 nm droplet size, was found to contain 15%, 75%, and 10% of oil, polyethylene glycol 400, and tween 80, respectively. The prepared pastes revealed a shear-thinning of pseudoplastic flow behavior. Flat-faced round tablets of 15 mm diameter and 5.6–11.2 mm thickness were successfully printed and illustrated good criteria for friability, weight variation, and content uniformity. Drug release was superior from SNEDDS-based tablets when compared to non-SNEDDS tablets. Scanning electron microscopy study of the 3DP tablets revealed a semi-porous surface that exhibited some curvature with the appearance of tortuosity and a gel porous-like structure of the inner section. GLMP and RSV demonstrated relative bioavailability of 159.50% and 245.16%, respectively. Accordingly, the developed 3DP tablets could be considered as a promising combined oral drug therapy used in treatment of metabolic disorders. However, clinical studies are needed to investigate their efficacy and safety.

OBSERVATIONS ON THE EFFECTS OF OMGA-3 FATTY ACIDS (W3 F.A.) AND FENOFIBRATE ON THE LIPID PROFILE OF THE PATIENTS SUFFERING FROM DIABETES MELLITUS TYPE-II

Introduction: In practice, control of LDL-C usually means intervention with a statin (occasionally combined with ezetimibe) where lifestyle interventions (diet and exercise) are insufciently effective. Aims &amp; objectives: Aim of the present study is to evaluate the efcacy of Omega-3 Fatty acids and Fenobrate in the treatment of dyslipidemia in the patients of Type-II Diabetes Mellitus with an objective to provide guidelines for better treatment of dyslipidemia in patients with Type-II Diabetes Mellitus. Material and method: the Department of Pharmacology, Darbhanga Medical College, Laheriasaria, with all facilities such as was furnished laboratory, necessary equipments and infrastructure. Total Lipid prole was be done by Enzymatic Method. Conclusion:We found that patients both total cholesterol at 6 weeks and 24 weeks were lower in Fenobrate Group compared to Omega-3 Fatty acid group.

Treatment of dyslipidemia in patients with cardiometabolic syndrome

Treatment of dyslipidemia in patients with cardiometabolic syndrome

Lipid Management in Patients with Endocrine Disorders: An Endocrine Society Clinical Practice Guideline.

This guideline will provide the practicing endocrinologist with an approach to the assessment and treatment of dyslipidemia in patients with endocrine diseases, with the objective of preventing cardiovascular (CV) events and triglyceride-induced pancreatitis. The guideline reviews data on dyslipidemia and atherosclerotic cardiovascular disease (ASCVD) risk in patients with endocrine disorders and discusses the evidence for the correction of dyslipidemia by treatment of the endocrine disease. The guideline also addresses whether treatment of the endocrine disease reduces ASCVD risk. This guideline focuses on lipid and lipoprotein abnormalities associated with endocrine diseases, including diabetes mellitus, and whether treatment of the endocrine disorder improves not only the lipid abnormalities, but also CV outcomes. Based on the available evidence, recommendations are made for the assessment and management of dyslipidemia in patients with endocrine diseases.

Current perspectives on the use of statins in the treatment of dyslipidaemic patients: focus on pitavastatin.

A meeting entitled ‘Current Perspective on the Use of Statins in the Treatment of Dyslipidemic Patients’ was held in Stresa, Italy, on 27–28th June 2019. The presentations covered the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines on dyslipidaemia, with discussion about the importance of controlling low-density lipoprotein cholesterol (LDL-C) and the pharmacological opportunities to reach the novel lipid goals. The roles of statins to manage dyslipidaemia in patients with different cardiovascular risks were also discussed. In particular, the efficacy and safety of pitavastatin for the treatment of dyslipidaemia were reviewed, highlighting its further advantages beyond LDL-C reduction. Therefore, the impact of statins on the glycaemic profile was discussed in view of the null/lower effect of pitavastatin as compared with other statins, as well as the interaction profile with other drugs commonly used. This meeting report summarizes the main messages of the discussion with a special focus on pitavastatin, whose main features in different settings are described.

Low-Density Lipoprotein Cholesterol Targets in Patients With Coronary Heart Disease in Extremadura (Spain): LYNX Registry.

BackgroundLow-density lipoprotein cholesterol (LDL-C) contributes decisively to the development of cardiovascular disease (CVD). In the LYNX registry we determined the rate of achievement of the target value of LDL-C, the use of lipid-lowering therapy (LLT) and the predictive factors of not reaching the target in patients with stable coronary heart disease (CHD).MethodsLYNX included consecutive patients with stable CHD treated at the University Hospital of Caceres, Extremadura (Spain) from September 2016 to September 2018, and those who must have an LDL-C target below 70 mg/dL according to the European Society of Cardiology (ESC) 2016 guidelines. The variables independently associated with the breach of the LDL-C objective were evaluated by multivariable logistic regression.ResultsA total of 674 patients with stable CHD were included. The average LDL-C levels were 68.3 ± 24.5 mg/dL, with 56.7% showing a level below 70 mg/dL. LLT was used by 96.7% of patients, 71.7% were treated with high-powered statins and 30.1% with ezetimibe. The risk of not reaching the target value of LDL-C was higher in women, in active smokers, and in those who had multivessel CHD or had atrial fibrillation. Patients with diabetes mellitus, those who took potent statins or co-administration treatment with ezetimibe were more likely to reach the target level of LDL-C.ConclusionsThe treatment of dyslipidemia in patients with chronic CHD remains suboptimal; however, an increasing number of very high-risk patients achieve the LDL-C objective, although there is still enormous potential to improve cardiovascular outcome through the use of more intensive LLT.

Suboptimal treatment of dyslipidemia in patients with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) patients often have dyslipidemia, and optimal treatment of dyslipidemia lowers the risk of cardiovascular disease and mortality. Our aim was to study the prescription of statin and low-density lipoprotein cholesterol treatment targets in NAFLD patients. Consecutive NAFLD patients attending five clinics in Asia were included in this study. The 10-year cardiovascular disease risk was calculated based on the Framingham Heart Study, and patients were categorized as moderate, high, or very high risk for cardiovascular disease on the basis of the American Association of Clinical Endocrinologist 2017 Guidelines. The low-density lipoprotein cholesterol treatment goal for each of the risk groups was 2.6, 2.6, and 1.8mmol/L, respectively. The data for 428 patients were analyzed (mean age 54.4±11.1years, 52.1% male). Dyslipidemia was seen in 60.5% (259/428), but only 43.2% (185/428) were on a statin. The percentage of patients who were at moderate, high, and very high risk for cardiovascular disease was 36.7% (157/428), 27.3% (117/428), and 36.0% (154/428), respectively. Among patients who were on a statin, 58.9% (109/185) did not achieve the treatment target. Among patients who were not on a statin, 74.1% (180/243) should be receiving statin therapy. The percentage of patients who were not treated to target or who should be on statin was highest among patients at very high risk for cardiovascular disease at 79.6% (78/98) or 94.6% (53/56), respectively. This study highlights the suboptimal treatment of dyslipidemia and calls for action to improve the treatment of dyslipidemia in NAFLD patients.

Atorvastatin in the Treatment of Dyslipidemic Patients with Very High Cardiovascular Risk and Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after ruling out other causes of hepatic steatosis. The aim of the study is to identify the role of statin therapy in dyslipidemic patients with very high cardiovascular risk and NAFLD in achieving low density lipoprotein (LDL) cholesterol targets while also evaluating the changes in liver enzymes levels. This prospective study included 140 patients with NAFLD, hyperlipidemia and elevated cardiovascular risk. Serum lipids were assessed and liver function tests were performed at baseline and at 6 months follow up in 10 mg/ 20 mg daily atorvastatin treatment schedule. The results showed that total cholesterol, LDL cholesterol and triglycerides were significantly reduced at 6 months follow-up, while high density lipoprotein (HDL) cholesterol has not undergone important changes. Statin treatment significantly improved alanine aminotransferase serum levels, whereas aspartate aminotransferase levels were not significantly reduced between baseline and follow-up. Although statin therapy appears to be safe and effective for use in patients with NAFLD, an insufficient treatment is commonly observed in clinical practice, in order to avoid liver damage . NAFLD is not only a major cause of liver related morbidity and mortality, but also an independent cardiovascular risk factor, with cardiovascular mortality being the most important cause of death. Therefore, detecting and modifying risk factors without impairing liver function is desirable.

Перспективные методы лечения дислипидемий у больных с НАЖБП

Перспективные методы лечения дислипидемий у больных с НАЖБП

Atorvastatin and carnitine combination versus atorvastatin alone impacts on the lipid profile of haemodialyzed patients: A randomised clinical trial

Introduction: Dyslipidemia is one of the most common problems in hemodialysis patients and healthcare system. Some studies have suggested the use of carnitine in the treatment of dyslipidemia in hemodialysis patients. This study was carried out aiming to evaluate the effect of atorvastatin and carnitine combination versus atorvastatin alone on the lipid profile of hemodialyzed patients. Methods: In this clinical trial, 50 hemodialysis patients referred to the educational centres of Tabriz University of Medical Sciences, Tabriz, Iran, for haemodialysis were enrolled. Patients were randomly assigned into two groups. In the first group, patients were treated with carnitine (1000 mg three times daily) and atorvastatin (10-80 mg/day based on the baseline lipid profile of the patients) and in the second group, the patients were treated with atorvastatin alone for six months. The levels of triglyceride (TG), cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and haemoglobin before and after intervention were compared. The side effects of carnitine administration were also evaluated. Results: Results showed that TG, cholesterol, and LDL levels were significantly lower in the carnitine group compared to those in the other group at the end of study (P &lt; 0.050). In addition, HDL and haemoglobin levels were significantly higher in the carnitine group in comparison to the other group (P &lt; 0.050). No major side effects of carnitine were observed among the patients. Conclusion: The use of carnitine plus atorvastatin combination is an effective and safe method in the treatment of dyslipidemia in patients undergoing hemodialysis without imposing significant side effects.

CONTROVERSIAL ISSUES IN THE TREATMENT OF DYSLIPIDEMIAS IN PATIENTS WITH DIABETES MELLITUS.

Patients with diabetes mellitus have an elevated cardiovascular risk. Lipid-lowering therapy is a successful strategy to prevent atherosclerotic events in these patients. Therefore, almost all professional societies recommend statin therapy for patients with diabetes under certain conditions. Despite this broad consensus, a number of controversial issues remain. Thus, it remains unclear in which patients the lipid parameters should be determined in the fasting state and in which postprandial values are sufficient. It is also an open issue whether all patients with diabetes should receive statin therapy and which goals should be achieved. While the benefit of statin-ezetimibe and statin-PCSK9-inhibition combinations has been shown in large outcome trials, results of outcome trials involving statins with triglyceride lowering drugs have been ambiguous. Thus, it is currently unclear which patients benefit from such combinations. Finally, the best strategy to address severe hypertriglyceridemia in patients with diabetes is unclear. This article discusses these issues and aims to provide help and information to practicing physicians taking care of patients with diabetes mellitus. (REV INVEST CLIN. 2018;70:237-43).