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1.
Current Drugs and Nutraceuticals for the Treatment of Patients with Dyslipidemias.
Scognamiglio, M, Costa, D, Sorriento, A, Napoli, C
Current pharmaceutical design. 2019;(1):85-95
Abstract
Coronary heart disease (CHD) remains the leading cause of disability and death in industrialized Countries. Among many conditions, which contribute to the etiology and progression of CHD, the presence of high low density lipoprotein-cholesterol (LDL-C) levels represents the major risk factor. Therefore, the reduction of LDL-C levels plays a key role in the management of patients with high or very high cardiovascular risk. Although statins represent the gold standard therapy for the reduction of cholesterol levels, these drugs do not allow to achieve target levels of LDL-C in all patients. Indeed, a significant number of patients resulted intolerants, especially when the dosage increased. The availability of new lipid-lowering drugs, such as ezetimibe and PCSK9 inhibitors, may represent an important alternative or complement to the conventional lipid-lowering therapies. However, long-term studies are still needed to define both efficacy and safety of use of these latter new drugs. Some nutraceuticals may become an adequate and effective support in the management of some patients. To date, several nutraceuticals with different mechanism of actions that provide a good tolerability are available as lipidlowering agents. In particular, the most investigated are red yeast rice, phytosterols, berberine, beta-glucans and soy. The aim of this review was to report recent data on the efficacy and safety of principle hypocholesterolemic drugs available and to evaluate the possible role of some nutraceuticals as support therapy in the management of patients with dyslipidemias.
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2.
Lipotoxicity in Kidney, Heart, and Skeletal Muscle Dysfunction.
Nishi, H, Higashihara, T, Inagi, R
Nutrients. 2019;(7)
Abstract
Dyslipidemia is a common nutritional and metabolic disorder in patients with chronic kidney disease. Accumulating evidence supports the hypothesis that prolonged metabolic imbalance of lipids leads to ectopic fat distribution in the peripheral organs (lipotoxicity), including the kidney, heart, and skeletal muscle, which accelerates peripheral inflammation and afflictions. Thus, lipotoxicity may partly explain progression of renal dysfunction and even extrarenal complications, including renal anemia, heart failure, and sarcopenia. Additionally, endoplasmic reticulum stress activated by the unfolded protein response pathway plays a pivotal role in lipotoxicity by modulating the expression of key enzymes in lipid synthesis and oxidation. Here, we review the molecular mechanisms underlying lipid deposition and resultant tissue damage in the kidney, heart, and skeletal muscle, with the goal of illuminating the nutritional aspects of these pathologies.
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3.
Current pharmacotherapeutic options for primary dyslipidemia in adults.
Cicero, AFG, Landolfo, M, Ventura, F, Borghi, C
Expert opinion on pharmacotherapy. 2019;(10):1277-1288
Abstract
INTRODUCTION Atherosclerotic cardiovascular disease (ASCVD) and its clinical manifestations, remain a leading cause of death and disability worldwide. One of the major risk factors of ASCVD is dyslipidemia and all the available guidelines suggest the importance of strategies for lipid control in a remarkable proportion of the general population. AREAS COVERED This review focuses on the therapeutic options available for the management of lipid disorders in adults. EXPERT OPINION A large body of evidence supports that statins are still the first-line option for the management of hypercholesterolemia in a large percentage of patients. Statins should be given at the appropriate dose and considering the differences in lipid-lowering potency across the different medications. The main current challenge in the treatment of lipid disorders is the need of improving patient adherence and persistence to lipid-lowering treatments beyond the drug choice and the target lipid component. To achieve this goal, the best strategy would be to treat the patients by using the appropriate drugs given at adequate doses to reach the treatment target. We should also avoid drug interactions, monitor possible untoward side effects and promote adherence to treatment by tailoring treatment strategies to each patient.
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Statins an oft-prescribed drug is implicated in peripheral neuropathy: The time to know more.
Al-Kuraishy, HM, Al-Gareeb, AI, Hussien, NR, Al-Naimi, MS, Rasheed, HA
JPMA. The Journal of the Pakistan Medical Association. 2019;(8):S108-S112
Abstract
Statins are hydroxymethylglutaryl-coenzyme A reductase inhibitors inhibit denovo cholesterol synthesis leading to reduction of serum cholesterol and low density lipoprotein as well as elevation of high density lipoprotein level. Statins are used in the treatment of dyslipidaemia, prevention of major cardiovascular events and complications. The potential role of statins in the induction of peripheral neuropathy has not been verified as most of statins induced-peripheral neuropathy had been reported as case reports. Also, statins therapy leads to noteworthy reduction of Coenzyme Q10, causing impairment of neuronal energy. The incidence of polyneuropathy was high with atorvastatin (65%) which is lipophilic, and relatively less with fluvastatin (54%) which is hydrophilic. Long-term statins therapy, mainly with atorvastatin and simvastatin, is linked with thedevelopment of peripheral neuropathy.
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5.
[PCSK9 inhibitors: What place in the management of dyslipidemia?].
Sabouret, P, Farnier, M, Puymirat, E
Presse medicale (Paris, France : 1983). 2019;(3 Pt 1):227-237
Abstract
PCSK9 protein is a key regulator of LDL receptor activity. Gain-of-function mutations in PCSK9 are one of the genetic causes of familial hypercholesterolemia. Conversely, loss-of-function mutations are associated with lower levels of LDL cholesterol and reduced coronary heart disease. Monoclonal antibodies targeting PCSK9 are highly efficacious in lowering LDL-C levels, with a good tolerability and safety profile. Two PCSK9 inhibitors, alirocumab and evolocumab, have demonstrated a cardiovascular benefit in addition to statin therapy in patients with established cardiovascular disease. A recent European consensus has defined the candidates for PCSK9 inhibitors, e.g., patients with established cardiovascular disease and patients with familial hypercholesterolemia in primary prevention, with substantially elevated LDL-C levels despite maximally tolerated statin with or without ezetimibe therapy.
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6.
Endothelial Function in Patients with Subclinical Hypothyroidism: A Meta-Analysis.
Gong, N, Gao, C, Chen, X, Fang, Y, Tian, L
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2019;(11):691-702
Abstract
The purpose of this meta-analysis was to determine whether patients with subclinical hypothyroidism (SCH) have impaired endothelial function, which is assessed by carotid intima-media thickness (C-IMT) and flow-mediated dilatation (FMD) of brachial artery. PubMed, Embase and Cochrane Library databases and the key studies references were searched in our study, prior to July 2017 for all language articles about FMD or C-IMT in SCH and euthyroid subjects. Two authors screened documents and extracted data by pre-established standard independently. The pooled estimate for continuous data was calculated using random-effects models. Statistical heterogeneity was evaluated using I2 statistics. Subgroup analyses were conducted to assess the robustness of the meta-analysis. Publication bias was examined with funnel plot analysis and Egger's test. In this meta-analysis, 10 studies with 760 subjects are related to FMD with SCH and 23 studies with 1521 subjects are related to C-IMT with SCH. The pooled estimate of the weighted mean difference (WMD) has revealed that SCH correlated with increased C-IMT [WMD 0.069 mm; 95% CI (0.042, 0.095); p<0.001] and decreased FMD [WMD -1.848%; 95% CI (-2.298, -1.399); p<0.001] with high heterogeneity.: Compared with EU controls, SCH was also associated with an increased diastolic blood pressure (DBP), systolic blood pressure (SBP), triglyceride (TG), total cholesterol (TC) levels, and low density lipoprotein cholesterol (LDL-C). This meta-analysis demonstrates that SCH is associated with endothelial dysfunction, which may relate with increased thyroid-stimulating hormone (TSH). Hypertension and dyslipidemia may play a crucial part in the development of endothelial dysfunction.
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7.
An updated review of lipid-modifying therapy.
Simons, LA
The Medical journal of Australia. 2019;(2):87-92
Abstract
Statin drugs reduce low-density lipoprotein (LDL)-cholesterol (LDL-C) and cardiovascular risk. Ezetimibe may be used to supplement statin therapy, or used alone in cases of statin intolerance. Statin-associated side effects do occur, especially muscle symptoms and new onset diabetes, but they do not detract from the benefits of statin therapy. Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce LDL-C and cardiovascular risk. Evolocumab is subsidised in Australia for patients with familial hypercholesterolaemia when LDL-C is not adequately controlled with maximum doses of statin or ezetimibe or when statin therapy is contraindicated. Fenofibrate reduces triglycerides and cardiovascular risk in patients with type 2 diabetes when triglycerides are elevated and high-density lipoprotein (HDL) is low. A role for dietary omega-3 fatty acids and esters in reducing cardiovascular risk remains controversial. All cases of secondary cardiovascular disease prevention merit intensive lipid therapy, unless a contraindication exists. Lipid therapy is justified in cases of primary prevention when absolute risk is high, especially when lipids are highly elevated or when multiple risk factors are present. Clinical management requires a focus on the predominant lipid disorder present, namely hypercholesterolaemia, hypertriglyceridaemia or combined hyperlipidaemia. There is an ongoing problem of poor long term persistence on lipid therapy, as well as reduced awareness by practitioners of poor risk factor control.
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8.
Dyslipidemia in Ischemia/Reperfusion Injury.
Mazo, T, D'Annunzio, V, Donato, M, Perez, V, Zaobornyj, T, Gelpi, RJ
Advances in experimental medicine and biology. 2019;:117-130
Abstract
Ischemic heart disease is the main cause of morbidity and mortality in the developed world. Although reperfusion therapies are currently the best treatment for this entity, the restoration of blood flow leads, under certain circumstances, to a form of myocardial damage called reperfusion injury. Several studies have shown that age, sex, smoking, diabetes and dyslipidemia are risk factors for cardiovascular diseases. Among these risk factors, dyslipidemias are present in 40% of patients with ischemic heart disease and represent the clinical factor with the greatest impact on the prognosis of patients with cardiovascular diseases. It is known that during reperfusion the increase of the oxidative stress is perhaps one of the most important mechanisms implicated in cell damage. That is why several researchers have studied protective mechanisms against reperfusion injury, such as the ischemic pre- and post- conditioning, making emphasis mainly on the reduction of oxidative stress. However, few of these efforts have been successfully translated into the clinical setting. The controversial results in regards to the relation between cardioprotective mechanisms and dyslipidemia/hypercholesterolemia are mainly due to the difference among quality, composition and the time of administration of hypercholesterolemic diets, as well as the difference in the species used in each of the studies. Therefore, in order to compare results, it is crucial that all variables that could modify the obtained results are taken into consideration.
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9.
Lipidome Abnormalities and Cardiovascular Disease Risk in HIV Infection.
Bowman, E, Funderburg, NT
Current HIV/AIDS reports. 2019;(3):214-223
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Abstract
PURPOSE OF REVIEW Human immunodeficiency virus (HIV) infection and its treatment with antiretroviral therapy (ART) are associated with lipid abnormalities that may enhance cardiovascular disease risk (CVD). RECENT FINDINGS Chronic inflammation persists in HIV+ individuals, and complex relationships exist among lipids and inflammation, as immune activation may be both a cause and a consequence of lipid abnormalities in HIV infection. Advances in mass spectrometry-based techniques now allow for detailed measurements of individual lipid species; improved lipid measurement might better evaluate CVD risk compared with the prognostic value of traditional assessments. Lipidomic analyses have begun to characterize dynamic changes in lipid composition during HIV infection and following treatment with ART, and further investigation may identify novel lipid biomarkers predictive of adverse outcomes. Developing strategies to improve management of comorbidities in the HIV+ population is important, and statin therapy and lifestyle modifications, including diet and exercise, may help to improve lipid levels and mitigate CVD risk.
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10.
Wendan decoction for dyslipidemia: Protocol for a systematic review and meta-analysis.
Feng, W, Ye, X, Lv, H, Hou, C, Chen, Y
Medicine. 2019;(3):e14159
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Abstract
BACKGROUND Dyslipidemia is one of the most popular metabolic diseases and an important risk factor for arteriosclerotic cardiovascular diseases. In China, Wendan decoction (WDD) has been widely used to treat hyperlipidemia. However, no systematic review has been found. In order to evaluate the efficacy and safety of WDD in the treatment of dyslipidemia, a meta-analysis and systematic evaluation are conducted. METHODS The randomized controlled trials (RCTs) evaluating the effectiveness and safety of WDD in the treatment of dyslipidemia will be enrolled. Data are mainly from 4 English databases (Pubmed, Embase, Cochrane Library, and Web of science) and 4 Chinese databases (Wanfang, CBM, CNKI, and VIP Database). The enrollment of RCTs is from the starting date of database establishment till December 15, 2018. Low density lipoprotein cholesterol is considered as the main outcome, while the serum concentrations of total cholesterol, triglyceride, high density lipoprotein cholesterol, apolipoprotein A, and apolipoprotein B are regarded as the secondary outcome. Safety indicators include liver enzyme, fasting blood glucose, and kidney function. The work such as selection of literature, data collection, quality evaluation of included literature, and assessment of publication bias will be conducted by 2 independent researchers. Meta-analysis will be performed by RevMan 5.0 software. RESULTS This study will provide high-quality evidence for the treatment of dyslipidemia with WDD in terms of effectiveness and safety. CONCLUSION The results of the study will help us determine whether WDD can effectively treat hyperlipidemia. PROSPERO REGISTRATION NUMBER PROSPERO CRD 42018114957.