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Nutrients Jun 2023Atherosclerotic cardiovascular disease (ASCVD) remains the major mortality cause in developed countries with hypercholesterolaemia being one of the primary modifiable... (Review)
Review
Atherosclerotic cardiovascular disease (ASCVD) remains the major mortality cause in developed countries with hypercholesterolaemia being one of the primary modifiable causes. Lifestyle intervention constitutes the first step in cholesterol management and includes dietary modifications along with the use of functional foods and supplements. Functional foods enriched with plant sterols/stanols have become the most widely used nonprescription cholesterol-lowering approach, despite the lack of randomized trials investigating their long-term safety and cardiovascular efficacy. The cholesterol-lowering effect of plant-sterol supplementation is well-established and a potential beneficial impact on other lipoproteins and glucose homeostasis has been described. Nevertheless, experimental and human observational studies investigating the association of phytosterol supplementation or circulating plant sterols with various markers of atherosclerosis and ASCVD events have demonstrated controversial results. Compelling evidence from recent genetic studies have also linked elevated plasma concentrations of circulating plant sterols with ASCVD presence, thus raising concerns about the safety of phytosterol supplementation. Thus, the aim of this review is to provide up-to-date data on the effect of plant sterols/stanols on lipid-modification and cardiovascular outcomes, as well as to discuss any safety issues and practical concerns.
Topics: Humans; Phytosterols; Hypercholesterolemia; Anticholesteremic Agents; Cholesterol; Atherosclerosis; Cardiovascular Diseases
PubMed: 37447172
DOI: 10.3390/nu15132845 -
Journal of the American College of... Jun 2019
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Topics: American Heart Association; Anticholesteremic Agents; Biomarkers; Cardiology; Cardiovascular Diseases; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Medication Therapy Management; PCSK9 Inhibitors; Risk Assessment; Risk Reduction Behavior; United States
PubMed: 30423393
DOI: 10.1016/j.jacc.2018.11.003 -
Endocrinology and Metabolism Clinics of... Sep 2022Inherited hypercholesterolemias include monogenic and polygenic disorders, which can be very rare (eg, cerebrotendinous xanthomatosis (CTX)) or relatively common (eg,... (Review)
Review
Inherited hypercholesterolemias include monogenic and polygenic disorders, which can be very rare (eg, cerebrotendinous xanthomatosis (CTX)) or relatively common (eg, familial combined hyperlipidemia [FCH]). In this review, we discuss familial hypercholesterolemia (FH), FH-mimics (eg, polygenic hypercholesterolemia [PH], FCH, sitosterolemia), and other inherited forms of hypercholesterolemia (eg, hyper-lipoprotein(a) levels [hyper-Lp(a)]). The prevalence, genetics, and management of inherited hypercholesterolemias are described and selected guidelines summarized.
Topics: Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols
PubMed: 35963626
DOI: 10.1016/j.ecl.2022.02.006 -
Journal of Atherosclerosis and... Dec 2022
Topics: Humans; Temperature; Hypercholesterolemia
PubMed: 36031359
DOI: 10.5551/jat.ED214 -
Journal of Atherosclerosis and... Aug 2021Sitosterolemia is an inherited metabolic disorder characterized by increased levels of plant sterols, such as sitosterol. This disease is caused by loss-of-function... (Review)
Review
Sitosterolemia is an inherited metabolic disorder characterized by increased levels of plant sterols, such as sitosterol. This disease is caused by loss-of-function genetic mutations in ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively), both of which play important roles in selective excretion of plant sterols from the liver and intestine, leading to failure to prevent absorption of food plant sterols. This disorder has been considered to be extremely rare. However, accumulated clinical data as well as genetics suggest the possibility of a much higher prevalence. Its clinical manifestations resemble those observed in patients with familial hypercholesterolemia (FH), including tendon xanthomas, hyper LDL-cholesterolemia, and premature coronary atherosclerosis. We provide an overview of this recessive genetic disease, diagnostic as well as therapeutic tips, and the latest diagnostic criteria in Japan.
Topics: Disease Management; Humans; Hypercholesterolemia; Intestinal Diseases; Japan; Lipid Metabolism, Inborn Errors; Phytosterols
PubMed: 33907061
DOI: 10.5551/jat.RV17052 -
Current Drug Targets 2018Despite the intensive research and progress in modern pharmacotherapy, hypercholesterolemia and related cardiovascular complications remain one of the leading causes of... (Review)
Review
Despite the intensive research and progress in modern pharmacotherapy, hypercholesterolemia and related cardiovascular complications remain one of the leading causes of mortality and disability in the modern world. A significant contribution to the treatment of hypercholesterolemia was made by the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9). This enzyme is responsible for the degradation of the low-density lipoprotein (LDL) receptor (LDLR) found at the surface of the plasma membrane in the liver and directly associated with serum LDL level. Limitations in standard therapy used in the treatment of lipid disorders have led to the development of new drugs, such as an inhibitor of PCSK9. Over the past years, the greatest achievement in discovering the PCSK9 inhibitor was made by designing monoclonal antibodies that disable PCSK9 to bind LDLR and RNA interference to reduce PCSK9 production, but one of the main disadvantages is costeffectiveness. In this review, we will summarize the most recent findings of basic and clinical studies which focus on PCSK9 function, regulation and therapeutic target for the treatment of hypercholesterolemia and associated cardiovascular diseases.
Topics: Animals; Antibodies, Monoclonal; Cardiovascular Diseases; Humans; Hypercholesterolemia; PCSK9 Inhibitors; Proprotein Convertase 9; RNA Interference; Receptors, LDL
PubMed: 29210646
DOI: 10.2174/1389450119666171205101401 -
Frontiers in Immunology 2021Phytochemicals derived from oats are reported to possess a beneficial effect on modulating dyslipidemia, specifically on lowering total and LDL cholesterol. However,... (Comparative Study)
Comparative Study Randomized Controlled Trial
The Prebiotic Effects of Oats on Blood Lipids, Gut Microbiota, and Short-Chain Fatty Acids in Mildly Hypercholesterolemic Subjects Compared With Rice: A Randomized, Controlled Trial.
Phytochemicals derived from oats are reported to possess a beneficial effect on modulating dyslipidemia, specifically on lowering total and LDL cholesterol. However, deeper insights into its mechanism remain unclear. In this randomized controlled study, we assigned 210 mildly hypercholesterolemic subjects from three study centers across China (Beijing, Nanjing, and Shanghai) to consume 80 g of oats or rice daily for 45 days. Plasma lipid profiles, short chain fatty acids (SCFAs), and fecal microbiota were measured. The results showed that total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) decreased significantly with both oats and rice intake after 30 and 45 days. The reduction in TC and non-HDL-C was greater in the participants consuming oats compared with rice at day 45 ( = 0.011 and 0.049, respectively). Oat consumption significantly increased the abundance of and , and the relative abundance of , , and , and decreased unclassified In the oat group, abundance was negatively correlated with LDL-C ( = 0.01, = -0.31) and, TC and LDL-C were negatively correlated to ( = 0.02, = -0.29; = 0.03, = -0.27, respectively). , , and were positively correlated with plasma butyric acid and valeric acid concentrations and negatively correlated to isobutyric acid. HDL-C was negatively correlated with valeric acid ( = 0.02, = -0.25) and total triglyceride (TG) was positively correlated to isovaleric acid ( = 0.03, = 0.23). Taken together, oats consumption significantly reduced TC and LDL-C, and also mediated a prebiotic effect on gut microbiome. , , , and , and plasma SCFA correlated with oat-induced changes in plasma lipids, suggesting prebiotic activity of oats to modulate gut microbiome could contribute towards its cholesterol-lowering effect.
Topics: Adult; Avena; Bacteria; Beijing; Biomarkers; Dysbiosis; Edible Grain; Fatty Acids, Volatile; Female; Gastrointestinal Microbiome; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Oryza; Prebiotics; Single-Blind Method; Time Factors; Treatment Outcome
PubMed: 34956218
DOI: 10.3389/fimmu.2021.787797 -
Current Cardiology Reports Apr 2019Identification of loci and common single-nucleotide polymorphisms (SNPs) that have modest effects on plasma lipids have been used to confirm or refute the causal role of... (Review)
Review
PURPOSE OF THE REVIEW
Identification of loci and common single-nucleotide polymorphisms (SNPs) that have modest effects on plasma lipids have been used to confirm or refute the causal role of lipid traits in the development of coronary heart disease (CHD), and as tools to identify individuals with polygenic hypercholesterolemia.
RECENT FINDINGS
Several groups have reported on the use of SNP scores in distinguishing individuals with a clinical diagnosis of familial hypercholesterolemia (FH) with a monogenic or polygenic etiology. We review evidence that those with monogenic FH have worse prognosis and discuss the possible mechanisms for this and their management. Individuals with a clinical phenotype of FH and a monogenic cause are at greater risk of CHD than those where no causative mutation can be found. The patients with polygenic hypercholesterolemia would not require elaborate cascade screening or secondary care input for their management.
Topics: Cardiovascular Diseases; Genetic Predisposition to Disease; Humans; Hypercholesterolemia; Mutation; Phenotype
PubMed: 31011892
DOI: 10.1007/s11886-019-1130-z -
Current Opinion in Lipidology Apr 2020This review summarizes the current knowledge regarding autosomal recessive hypercholesterolemia (ARH) and provides new insight into the natural history and therapeutic... (Review)
Review
PURPOSE OF REVIEW
This review summarizes the current knowledge regarding autosomal recessive hypercholesterolemia (ARH) and provides new insight into the natural history and therapeutic management of this lipid disorder.
RECENT FINDINGS
Novel homozygous and compound heterozygous ARH-causing mutations have been reported in the literature, to date. The long-term follow-up of a cohort of ARH patients demonstrated that, despite intensive treatment with conventional lipid-lowering therapies, their low-density lipoprotein (LDL) cholesterol levels remain far from target and this translates into a poor cardiovascular prognosis. ARH is also associated with increased risk of developing aortic valve stenosis. However, lomitapide, a microsomal triglyceride transfers protein inhibitor, may represent a new opportunity for the effective treatment of ARH.
SUMMARY
ARH is an ultrarare disorder of LDL metabolism caused by mutations in the LDLRAP1 gene. It is inherited as a recessive trait and causative mutations, though heterogeneous, are all predicted to be loss-of-function. Recent investigations have demonstrated that ARH can be considered a phenocopy of homozygous familial hypercholesterolemia, where the risk of atherosclerotic cardiovascular diseases and aortic valve stenosis remains elevated despite conventional therapies. The combination of lomitapide with the conventional LDL-C-lowering medications appears to be a promising approach to treat this condition.
Topics: Animals; Anticholesteremic Agents; Benzimidazoles; Humans; Hypercholesterolemia; Lipid Metabolism; Lipoproteins, LDL; Mutation; Hyperlipoproteinemia Type III
PubMed: 32011344
DOI: 10.1097/MOL.0000000000000664 -
Herz Sep 2020The VOYAGER meta-analysis reported on the low-density lipoprotein cholesterol (LDL-C)-lowering effect of commonly used statins in Caucasian subjects. As there is limited... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The VOYAGER meta-analysis reported on the low-density lipoprotein cholesterol (LDL-C)-lowering effect of commonly used statins in Caucasian subjects. As there is limited literature available on the efficacy of statins in Asian populations, the current meta-analysis compared the effects of rosuvastatin and atorvastatin on LDL-C levels in an East Asian population.
METHODS
The MEDLINE, PubMed, Embase, Cochrane Library, and Web of Science databases were searched for randomized controlled trials comparing lipid-lowering effects of rosuvastatin and atorvastatin in an East Asian population. Data on the study design, participant characteristics, and outcomes were extracted. Odds ratios (OR), weighted mean differences (WMD), or standardized mean differences were calculated using the random-effects model.
RESULTS
The meta-analysis comprised 16 randomized controlled trials with 5930 participants. Compared with atorvastatin, patients treated with rosuvastatin had a significant reduction in LDL-C: WMD = -7.15 mg/dl (95% confidence intervals [CI]: -10.71--3.60) mg/dl, p < 0.0001. Meta-regression analyses revealed no significant association between the superior benefits of rosuvastatin and other variables including age, sex, baseline LDL-C level, and follow-up duration. Additionally, the rosuvastatin group of patients, who were treated with half the dose of atorvastatin, achieved a significantly greater reduction in LDL-C levels (WMD = -3.57; 95% CI: -5.40--1.74 mg/dl, p < 0.001). Both rosuvastatin and atorvastatin were well tolerated, with similar incidences of adverse events.
CONCLUSION
Similar to the VOYAGER meta-analysis, which reported a greater efficacy of rosuvastatin in comparison with atorvastatin and simvastatin in Caucasian patients, we found that the efficacy of rosuvastatin was superior to atorvastatin in East Asian patients with hypercholesterolemia.
Topics: Atorvastatin; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Rosuvastatin Calcium; Treatment Outcome
PubMed: 30483816
DOI: 10.1007/s00059-018-4767-2