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Current Atherosclerosis Reports Mar 2013Whether cholesterol is implicated in the pathogenesis of Alzheimer's disease (AD) is still controversial. Several studies that explored the association between lipids... (Review)
Review
Whether cholesterol is implicated in the pathogenesis of Alzheimer's disease (AD) is still controversial. Several studies that explored the association between lipids and/or lipid-lowering treatment and AD indicate a harmful effect of dyslipidemia on AD risk. The findings are supported by genetic linkage and association studies that have clearly identified several genes involved in cholesterol metabolism or transport as AD susceptibility genes, including apolipoprotein E (APOE), apolipoprotein J (APOJ, CLU), ATP-binding cassette subfamily A member 7(ABCA7), and sortilin-related receptor (SORL1). Functional cell biology studies further support a critical involvement of lipid raft cholesterol in the modulation of Aβ precursor protein processing by β-secretase and γ-secretase resulting in altered Aβ production. However, conflicting evidence comes from epidemiological studies showing no or controversial association between dyslipidemia and AD risk, randomized clinical trials observing no beneficial effect of statin therapy, and cell biology studies suggesting that there is little exchange between circulating and brain cholesterol, that increased membrane cholesterol level is protective by inhibiting loss of membrane integrity through amyloid cytotoxicity, and that cellular cholesterol inhibits colocalization of β-secretase 1 and Aβ precursor protein in nonraft membrane domains, thereby increasing generation of plasmin, an Aβ-degrading enzyme. The aim of this article is to provide a comprehensive review of the findings of epidemiological, genetic, and cell biology studies aiming to elucidate the role of cholesterol in the pathogenesis of AD.
Topics: Alzheimer Disease; Dyslipidemias; Humans; Lipid Metabolism; Lipids; Prognosis; Risk Factors
PubMed: 23328907
DOI: 10.1007/s11883-012-0307-3 -
Nutrients Nov 2022Currently, the nutraceutical approach to treat dyslipidaemia is increasing in use, and in many cases is used by physicians as the first choice in the treatment of... (Review)
Review
Currently, the nutraceutical approach to treat dyslipidaemia is increasing in use, and in many cases is used by physicians as the first choice in the treatment of patients with borderline values. Nutraceuticals represent an excellent opportunity to treat the preliminary conditions not yet showing the pathological signs of dyslipidaemia. Their general safety, the patient's confidence, the convincing proof of efficacy and the reasonable costs prompted the market of new preparations. Despite this premise, many nutraceutical products are poorly formulated and do not meet the minimum requirements to ensure efficacy in normalizing blood lipid profiles, promoting cardiovascular protection, and normalizing disorders of glycemic metabolism. In this context, bioaccessibility and bioavailability of the active compounds is a crucial issue. Little attention is paid to the proper formulations needed to improve the overall bioavailability of the active molecules. According to these data, many products prove to be insufficient to ensure full enteric absorption. The present review analysed the literature in the field of nutraceuticals for the treatment of dyslipidemia, focusing on resveratrol, red yeast rice, berberine, and plant sterols, which are among the nutraceuticals with the greatest formulation problems, highlighting bioavailability and the most suitable formulations.
Topics: Humans; Dyslipidemias; Dietary Supplements; Phytosterols; Lipids; Berberine
PubMed: 36432457
DOI: 10.3390/nu14224769 -
Cardiovascular Diabetology 2013Type 2 diabetes (T2D) is a strong, independent risk factor for cardiovascular (CV) and cerebrovascular outcomes. Meta-analysis of five randomised clinical trials (n =... (Review)
Review
Type 2 diabetes (T2D) is a strong, independent risk factor for cardiovascular (CV) and cerebrovascular outcomes. Meta-analysis of five randomised clinical trials (n = 33,040) showed that, although intensive versus standard glycaemic control significantly reduced CV events in people with T2D, the reduction was less than that achieved with lipid-lowering or antihypertensive treatment. Furthermore, fasting plasma glucose (FPG) concentrations were a modest predictor for CV risk in people without T2D. Thus, although effective glycaemic control is important for the prevention/management of T2D, other risk factors must be addressed to effectively reduce CV risk. Reducing low-density lipoprotein-cholesterol levels using statins significantly reduces CV risk in people with and without T2D. Although statins are generally safe and well tolerated, conflicting data exist regarding the diabetogenic effects of some statins. Based on recent clinical trial data, the US Food and Drug Administration have changed the labelling of all statins to include 'an effect of statins on incident diabetes and increases in haemoglobin A1c and/or FPG'. However, the literature suggests that the beneficial effects of most statins on CV risk continue to outweigh their diabetogenic risks and that statins should remain as first-line therapy for the majority of people with dyslipidaemia and metabolic syndrome or T2D. Mechanisms explaining the potentially higher incidence of T2D with statin therapy have not been confirmed. However, independent predictors for statin-associated T2D appear to include elevated levels of baseline FPG, BMI, blood pressure and fasting triglycerides. Moreover, although some statins (for example, atorvastatin) are associated with increased haemoglobin A1c levels in patients receiving intensive but not moderate therapy, other statins (for example, pitavastatin) have demonstrated neutral or favourable effects on glucose control in patients with and without T2D or metabolic syndrome. The potential diabetogenic effects of statins may therefore differ between drugs. In conclusion, conflicting data exist regarding the diabetogenic effects of statins. Further studies are required to understand whether all statins have the same effect and whether some patient groups are at higher risk than others. Meanwhile, results suggest that the net CV benefit favours the use of statin therapy in patients with dyslipidaemia, irrespective of T2D risk.
Topics: Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Interactions; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Metabolic Syndrome; Patient Selection; Quinolines; Risk Factors; Treatment Outcome
PubMed: 23819776
DOI: 10.1186/1475-2840-12-S1-S3 -
Genes Jul 2021The genetic screening program for familial hypercholesterolemia (FH) in the Netherlands, which was embraced by the Dutch Ministry of Health from 1994 to 2014, has led to... (Review)
Review
The genetic screening program for familial hypercholesterolemia (FH) in the Netherlands, which was embraced by the Dutch Ministry of Health from 1994 to 2014, has led to twenty years of identification of at least 1500 FH cases per year. Although funding by the government was terminated in 2014, the approach had proven its effectiveness and had built the foundation for the development of more sophisticated diagnostic tools, clinical collaborations, and new molecular-based treatments for FH patients. As such, the community was driven to continue the program, insurance companies were convinced to collaborate, and multiple approaches were launched to find new index cases with FH. Additionally, the screening was extended, now also including other heritable dyslipidemias. For this purpose, a diagnostic next-generation sequencing (NGS) panel was developed, which not only comprised the culprit , , and genes, but also 24 other genes that are causally associated with genetic dyslipidemias. Moreover, the NGS technique enabled further optimization by including pharmacogenomic genes in the panel. Using such a panel, more patients that are prone to cardiovascular diseases are being identified nowadays and receive more personalized treatment. Moreover, the NGS output teaches us more and more about the dyslipidemic landscape that is less straightforward than we originally thought. Still, continuous progress is being made that underlines the strength of genetics in dyslipidemia, such as discovery of alternative genomic pathogenic mechanisms of disease development and polygenic contribution.
Topics: Awareness; Dyslipidemias; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Hyperlipoproteinemia Type II; Netherlands
PubMed: 34440342
DOI: 10.3390/genes12081168 -
Current Opinion in Lipidology Jun 2019The purpose of the review is to discuss recent advances in microRNA (miRNA) regulation of lipid metabolism and highlight the importance of miRNA-mediated gene regulation... (Review)
Review
PURPOSE OF REVIEW
The purpose of the review is to discuss recent advances in microRNA (miRNA) regulation of lipid metabolism and highlight the importance of miRNA-mediated gene regulation in dyslipidemia and fatty liver disease. This article reviews examples of miRNAs that bridge disparate metabolic pathways in the liver. For example, we highlight miRNAs that are regulated by the sterol-sensing pathway in the liver that in turn regulate cellular or systemic cholesterol, fatty acid, and glucose levels.
RECENT FINDINGS
The most widely studied of these miRNAs are miR-33a/b; however, we recently reported that miRNAs in the miR-183/96/182 cluster are also likely regulated by hepatic cholesterol content and mediate the observed glucose-lowering effects of the bile acid sequestrant colesevelam through the sterol-sensing pathway. In addition, several other hepatic and adipose miRNAs have been recently demonstrated to be key regulators of cellular lipid synthesis, storage, and catabolism, as well as systemic lipid metabolism. Moreover, many of these miRNAs are altered in fatty liver disease and dyslipidemia.
SUMMARY
miRNAs are not just fine-tuners of lipid metabolism, but critical regulatory factors in lipid homeostasis and health. Loss of these miRNA regulatory modules very likely contributes to the underlying metabolic defects observed in lipid disorders.
Topics: Animals; Dyslipidemias; Humans; Lipid Metabolism; MicroRNAs
PubMed: 30985366
DOI: 10.1097/MOL.0000000000000603 -
Seminars in Dialysis Jul 2018Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Although numerous modifiable risk factors in the pathogenesis of CVD and its... (Review)
Review
Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Although numerous modifiable risk factors in the pathogenesis of CVD and its associated mortality have been identified, dyslipidemia remains to be a key focus for therapy. In this regard, significant progress has been made in reducing cardiovascular mortality via the use of lipid-lowering agents such as HMG CoA reductase inhibitors (statins). Yet, despite the disproportionate risk of CVD and mortality in patients with advanced chronic and end stage renal disease (ESRD), treatment of dyslipidemia in this patient population has not been associated with a notable improvement in outcomes. Furthermore, observational studies have not consistently found an association between dyslipidemia and poor outcomes in patients with ESRD. However, it is imperative that examination of dyslipidemia and its association with outcomes take place in the context of the many factors that are unique to kidney disease and may contribute to the abnormalities in lipid metabolism in patients with ESRD. Understanding these intricacies and distinct features will be vital not only to the interpretation of the available clinical data in regards to outcomes, but also to the individualization of lipid therapy in ESRD. In this review, we will examine the nature and underlying mechanisms responsible for dyslipidemia, the association of serum lipids and lipoprotein concentrations with outcomes and the results of major trials targeting cholesterol (mainly statins) in patients with ESRD.
Topics: Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Failure, Chronic; Renal Dialysis
PubMed: 29707830
DOI: 10.1111/sdi.12706 -
Neurosurgical Review Dec 2021Dyslipidemia is a well-established risk factor for coronary artery disease. However, the effect on cerebral artery disease, and more specifically the rupture risk of... (Review)
Review
Dyslipidemia is a well-established risk factor for coronary artery disease. However, the effect on cerebral artery disease, and more specifically the rupture risk of intracranial aneurysms, is unclear and has not yet been reviewed. We therefore performed a systematic review to investigate associations between different types of dyslipidemia and incidence of aneurysmal subarachnoid hemorrhage (aSAH). We used the MEDLINE, Embase, and Web of Science databases to identify clinical trials that compared the rupture risk among SAH patients with or without dyslipidemia. The risk of bias in each included study was evaluated using the Critical Appraisal Skills Program (CASP). Of 149 unique citations from the initial literature search, five clinical trials with a case-control design met our eligibility criteria. These studies compared aSAH patients to patients with unruptured aneurysms and found an overall inverse relationship between hypercholesterolemia and rupture risk of intracranial aneurysms. The quality assessment classified all included studies as high risk of bias. The evidence indicates that hypercholesterolemia is associated with a reduced rupture risk of intracranial aneurysms. However, it is not clear whether this relation is due to the dyslipidemic condition itself or the use of antihyperlipidemic medication.
Topics: Aneurysm, Ruptured; Dyslipidemias; Humans; Intracranial Aneurysm; Risk Factors; Subarachnoid Hemorrhage
PubMed: 33704595
DOI: 10.1007/s10143-021-01515-3 -
BMC Cardiovascular Disorders May 2022Non-communicable diseases like systemic arterial hypertension (SAH) and dyslipidemia are poorly studied in terms of patient journey aspects. This semi-systematic review... (Review)
Review
BACKGROUND AND OBJECTIVE
Non-communicable diseases like systemic arterial hypertension (SAH) and dyslipidemia are poorly studied in terms of patient journey aspects. This semi-systematic review provides evidence synthesis for the management of SAH and dyslipidemia in Brazil and also discusses challenges faced by patients at the local level along with a suggested care approach by local experts.
METHODS
A semi-systematic review using both structured literature databases (Embase and Medline) and unstructured scientific records (WHO, IPD, MOH and Google) on hypertension and dyslipidemia in the English language from 2010 to 2019 was performed by reviewers. After two-level screening based on pre-defined criteria, patient journey touchpoints and prevalence information were extracted from the included articles. Data gaps were bridged through the insights of local experts.
RESULTS
Prevalence of hypertension and dyslipidemia in Brazil were 23% and 40.8%, respectively. Awareness of dyslipidemia was found in a larger proportion (58.1%) than in SAH (22.2%). Similarly, screening for hypertension (97%) and dyslipidemia (55.4%) were found to be effective, while treatment was (62.9%) and (30.0%) for hypertension and dyslipidemia, respectively.
CONCLUSION
There were important gaps on patient awareness and treatment of dyslipidemia and hypertension. Limited patient education, regional disease distribution, and treatment allocation, along with limited resources for diagnosis and treatment are the key challenges.
Topics: Brazil; Dyslipidemias; Humans; Hypertension; Prevalence
PubMed: 35597901
DOI: 10.1186/s12872-022-02669-8 -
Frontiers in Bioscience (Scholar... Mar 2024Disruption of lipoprotein metabolism plays an important role in the development of several cardiovascular, inflammatory, and metabolic diseases. This review examines the... (Review)
Review
Disruption of lipoprotein metabolism plays an important role in the development of several cardiovascular, inflammatory, and metabolic diseases. This review examines the importance of different types of lipoproteins and the role they play in the development of dyslipidemia in obesity. The causes and consequences associated with the disruption of lipid metabolism and its significance in the pathogenesis of obesity are considered. The relationship between such pathological processes, which occur alongside obesity as dyslipidemia and inflammation, is determined. In view of the current efficacy and toxicity limitations of currently approved drugs, natural compounds as potential therapeutic agents in the treatment of obesity are considered in the review. The complex mechanisms of lipid metabolism normalization in obesity found for these compounds can serve as one of the confirmations of their potential efficacy in treating obesity. Nanoparticles can serve as carriers for the considered drugs, which can improve their pharmacokinetic properties.
Topics: Humans; Lipoproteins; Obesity; Dyslipidemias; Cardiovascular System; Inflammation
PubMed: 38538342
DOI: 10.31083/j.fbs1601008 -
Clinical Gastroenterology and... Aug 2018
Review
Topics: Disease Management; Dyslipidemias; Humans; Liver Diseases
PubMed: 29684459
DOI: 10.1016/j.cgh.2018.04.023