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1.
Bempedoic Acid: A New Tool in the Battle Against Hyperlipidemia.
Powell, J, Piszczatoski, C
Clinical therapeutics. 2021;(2):410-420
Abstract
PURPOSE This article discusses the pharmacology of bempedoic acid, the trials that led to United States Food and Drug Administration (FDA) approval of its use, and the overall safety and efficacy of this therapy in heterozygous familial hypercholesterolemia, established atherosclerotic cardiovascular disease (ASCVD), and hyperlipidemia. METHODS A database search of PubMed and ClinicalTrials.gov was conducted for articles published between January 2012 to September 2020 and containing the key words bempedoic acid, ezetimibe, Nexletol and Nexlizet. Trials from the CLEAR series were selected, as they played a pivotal role in the establishment of FDA approval, along with additional trials published after FDA approval, which provided novel evidence on the use of bempedoic acid in the treatment of hypercholesterolemia. Publications that were not randomized, controlled trials were not included in this review. Only randomized controlled trials in which ezetimibe was used in conjunction with bempedoic acid were included in this review as they were relevant to the new FDA approval of bempedoic acid. FINDINGS The findings of the present review show that bempedoic acid is both an effective and well-tolerated option for the treatment of hypercholesterolemia when used without ezetimibe in addition to standard therapy. It also appears that the combination with ezetimibe increases the cholesterol-lowering effect more than either agent alone when added to standard therapy. IMPLICATIONS Hypercholesteremia continues to be a major contributing factor leading to ASCVD. Bempedoic acid is an additional treatment option, along with both statins and diet and exercise, for reducing cholesterol levels and ASCVD events. With the new FDA approval, bempedoic acid may offer an effective therapy for reducing low-density lipoprotein cholesterol in patients at high risk for cardiovascular events due to established ASCVD or heterozygous familial hypercholesterolemia.
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Bempedoic acid as adjunct for traditional lipid-lowering therapy in patients with hyperlipidaemia.
Schimmenti, C, Sucato, V, Manzone, E, Cancellieri, G, Mortillaro, F, Novo, G, Galassi, AR, Venturella, F
Coronary artery disease. 2021;(4):340-344
Abstract
Statin therapy has been the cornerstone for the reduction of cholesterol and circulating low-density lipoprotein (LDL) in patients with cardiovascular diseases. However, statin monotherapy has disadvantages attributable to myopathies and to the insufficient cholesterol reduction observed in some patients. There is a need for new well-tolerated therapies for lowering LDL. This review will focus on bempedoic acid in combination with traditional statin therapy or other lipid-lowering agents and its emerging role in LDL-C lowering. Bempedoic acid is also a viable alternative for reducing LDL cholesterol in the treatment of some patients suffering from heterozygous familial hypercholesterolemia.
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3.
Dietary Fiber: An Opportunity for a Global Control of Hyperlipidemia.
Nie, Y, Luo, F
Oxidative medicine and cellular longevity. 2021;:5542342
Abstract
Dietary fiber has a long history in the intervention study of hyperlipidemia. In this review, current understandings of structures, sources, and natures of various kinds of dietary fibers (DFs) were analyzed first. Available evidences for the use of different varieties of DFs in the lipid-lowering action both in vitro and in vivo were subsequently classified, including both soluble ones, such as glucans, pectins, and gums, and insoluble ones, including arabinooxylans and chitosans, in order to draw a primary conclusion of their dose and molecular weight relationship with lipid-lowering effect. Their potential mechanisms, especially the related molecular mechanism of protective action in the treatment and prevention of hyperlipidemia, were summarized at last. Five major mechanisms are believed to be responsible for the antihyperlipidemic benefits of DFs, including low levels of energy, bulking effect, viscosity, binding capacity, and fermentation thus ameliorating the symptoms of hyperlipidemia. From the molecular level, DFs could possibly affect the activities of HMG-CoA reductase, LDL receptors, CYP7A1, and MAPK signaling pathway as well as other lipid metabolism-related target genes. In summary, dietary fibers could be used as alternative supplements to exert certain lipid-lowering effects on humans. However, more clinical evidence is needed to strengthen this proposal and its fully underlying mechanism still requires more investigation.
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4.
Abdominal and gluteofemoral fat depots show opposing associations with postprandial lipemia.
Christiansen, MR, Ureña, MG, Borisevich, D, Grarup, N, Martínez, JA, Oppert, JM, Sørensen, TI, Hansen, T, Blaak, EE, Kilpeläinen, TO
The American journal of clinical nutrition. 2021;(4):1467-1475
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Abstract
BACKGROUND High postprandial lipemia is associated with increased risk of cardiovascular disease, independently of fasting lipid concentrations. Abdominal and gluteofemoral fat depots handle lipoproteins differently, which could affect postprandial lipemia and contribute to the relation between abdominal fat distribution and cardiovascular disease risk. OBJECTIVES We aimed to study the influences of higher abdominal compared with gluteofemoral fat on postprandial lipemia after a high-fat meal in individuals with obesity. METHODS A total of 755 adults with obesity from a randomized controlled trial in 7 European countries consumed a liquid high-fat meal. Concentrations of triglycerides (TG), glycerol, free fatty acids, and the cholesterol component of remnant-like particles (RLP), LDL, and HDL were measured postprandially for 3 h. Associations of waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR) with changes in postprandial lipid concentrations, adjusted for fasting concentrations and BMI, were examined using linear regression models. To assess whether the association of WHR with postprandial lipemia could be causal, we performed instrumental variable analyses using a genetic score of 442 variants known to be associated with WHR adjusted for BMI in 2-stage least-squares regression models. RESULTS WHR was associated with higher TG and RLP cholesterol concentrations, independent of fasting lipid concentrations and BMI. Instrumental variable analyses suggested that the associations of WHR with postprandial TG (β = 0.038 μmol/L*min, SE = 0.019 μmol/L*min, P = 0.044) and RLP cholesterol concentrations (β = 0.059 mmol/L, SE = 0.025 mmol/L, P = 0.020) may be causal. WC and HC showed opposite effects: higher WC was associated with higher TG and RLP cholesterol concentrations whereas higher HC was associated with lower concentrations. CONCLUSIONS Our results suggest that higher fat deposition abdominally versus gluteofemorally may be causally associated with elevated postprandial lipemia after a high-fat meal, independent of fasting lipid concentrations and BMI. Furthermore, higher abdominal and gluteofemoral fat depots show opposing effects on postprandial lipemia.This trial was registered at www.isrctn.com as ISRCTN25867281.
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Clinical hemocompatibility of double-filtration lipoprotein apheresis comparing polyethersulfone and ethylene-vinyl alcohol copolymer membranes.
Krieter, DH, Jeyaseelan, J, Rüth, M, Lemke, HD, Wanner, C, Drechsler, C
Artificial organs. 2021;(9):1104-1113
Abstract
Activation of the complement system and leukocytes by blood-membrane interactions may further promote arteriosclerosis typically present in patients on lipoprotein apheresis. As clinical data on the hemocompatibility of lipoprotein apheresis are scarce, a controlled clinical study comparing two different types of plasma separation and fractionation membranes used in double-filtration lipoprotein apheresis was urgently needed, as its outcome may influence clinical decision-making. In a prospective, randomized, crossover controlled trial, eight patients on double-filtration lipoprotein apheresis were subjected to one treatment with recent polyethersulfone (PES) plasma separation and fractionation membranes and one control treatment using a set of ethylene-vinyl alcohol copolymer (EVAL) membranes. White blood cell (WBC) and platelet (PC) counts, complement factor C5a and thrombin-antithrombin III (TAT) concentrations were determined in samples drawn at defined times from different sites of the extracorporeal blood and plasma circuit. With a nadir at 25 minutes, WBCs in EVAL decreased to 33.5 ± 10.7% of baseline compared with 63.8 ± 22.0% at 20 minutes in PES (P < .001). The maximum C5a levels in venous blood reentering the patients were measured at 30 minutes, being 30.0 ± 11.2 µg/L with EVAL and 12.3 ± 9.0 µg/L with PES (P < .05). The highest C5a concentrations were found in plasma after the plasma filters (EVAL 56.1 ± 22.0 µg/L at 15 minutes vs PES 23.3 ± 15.2 µg/L at 10 minutes; P < .001). PC did not significantly decrease over time with both membrane types, whereas TAT levels did not rise until the end of the treatment without differences between membranes. Regarding lipoprotein(a) and low-density lipoprotein (LDL) cholesterol removal, both membrane sets performed equally. Compared with EVAL, PES membranes cause less leukocyte and complement system activation, the classical parameters of hemocompatibility of extracorporeal treatment procedures, at identical treatment efficacy. Better hemocompatibility may avoid inflammation-promoting effects through blood-material interactions in patients requiring double-filtration lipoprotein apheresis.
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Aerobic exercise improves postprandial inflammatory and hemostatic markers after a high-fat meal: a randomized crossover study.
Teixeira, BC, Krüger, RL, Farinha, JB, Boeno, FP, Macedo, RCO, Fonseca, GA, Bandinelli, E, Duarte, MMMF, Reischak-Oliveira, A
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2021;(6):637-643
Abstract
Exercise intensity modulates postprandial lipemia. However, its effect on hemostatic and pro- and anti-inflammatory markers in the postprandial state is still unknown. Eleven young males performed a 2-day trial on different conditions: (i) REST rest for 45 min; (ii) MIE: moderate-intensity exercise; and (iii) HIE: heavy-intensity exercise. Experimental conditions were performed in the evening. On the following morning, blood samples were taken in the fasted state (0 h) and at 1, 3, and 5 h after the consumption of a high-fat meal (HFM). Interleukin-10 (IL-10) levels were higher in the HIE vs. MIE trial at 0 and 1 h (p < 0.033) and IL-10 incremental area under the curve (iAUC) was greater in the MIE (p = 0.027) and HIE (p = 0.045) trials vs. REST. Lower levels of anti-coagulation factor VII (FVII) were observed at 1 h in the MIE condition vs. REST (p = 0.043). In comparison with REST, MIE improved hemostatic (FVII) and anti-inflammatory markers (IL-10 iAUC) whereas HIE enhanced IL-10 in the postprandial state. Regardless of the exercise intensity, aerobic exercise mitigates the deleterious consequences of an HFM. Novelty: Prior aerobic exercise at moderate-intensity attenuates next day's postprandial FVII and IL-10 levels whereas exercise performed at heavy-intensity increases IL-10 levels. Moderate-intensity exercise may be more beneficial to improve hemostatic (FVII) and anti-inflammatory (IL-10) responses while heavy-intensity exercise may improve anti-inflammatory (IL-10) levels only.
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Is a treat-to-target approach to lipid-lowering therapy appropriate in patients with chronic kidney disease? A prospective French cohort study.
Massy, ZA, Kolla, E, Ferrières, J, Bruckert, E, Lambert, O, Mansencal, N, Laville, M, Frimat, L, Fouque, D, Combe, C, et al
Journal of nephrology. 2021;(5):1467-1477
Abstract
BACKGROUND Whereas European guidelines recommend adjusting lipid-lowering therapy (LLT) to meet prespecified targets ('treat-to-target') for low-density lipoprotein cholesterol (LDL-C), other guidelines do not ('fire and forget'). In a large observational prospective cohort, we sought to evaluate which strategy could be associated with better cardiovascular outcomes in chronic kidney disease (CKD). METHODS In CKD-REIN, patients (CKD stages 3 and 4) on LLT were categorized according to achievement of LDL-C targets for high and very high cardiovascular risk (< 2.6 and < 1.8 mmol/L, respectively) at baseline. Primary outcome was fatal/non-fatal atheromatous cardiovascular disease (CVD). Secondary outcomes were non-atheromatous CVD, atheromatous or non-atheromatous CVD, and major adverse cardiovascular events. RESULTS The population comprised 1521 patients (68 ± 12 years, 31% women, mean estimated glomerular filtration rate [eGFR] 35 mL/min/1.73 m2). Overall, 523 (34%) met their LDL-C targets at baseline. Median follow-up was 2.9 years (interquartile range 2.2-3.0). Incidence rates per 100 patient-years were 6.2% (95% confidence interval [CI] 5.5-7.0) for atheromatous CVD, 9.2% (8.3-10.1) for non-atheromatous CVD, 15.2% (14.0-16.4) for atheromatous/non-atheromatous CVD, and 6.3% (5.5-7.1) for major adverse cardiovascular events. Corresponding rates in patients who achieved targets were 6.6%, 9.8%, 16.1%, and 6.3%, respectively. Target achievement was not associated with risk of fatal/non-fatal atheromatous CVD (adjusted hazard ratio 1.04, 95% CI 0.76-1.44, p = 0.77) or fatal/non-fatal atheromatous or non-atheromatous CVD (0.98, 0.78-1.23, p = 0.91). CONCLUSIONS These findings do not appear to support a treat-to-target approach in CKD patients on LLT, and may favor the hypothesis of an advantage of fire-and-forget. Randomized trials are needed to confirm this theory.
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Almond Bioaccessibility in a Randomized Crossover Trial: Is a Calorie a Calorie?
Nishi, SK, Kendall, CWC, Bazinet, RP, Hanley, AJ, Comelli, EM, Jenkins, DJA, Sievenpiper, JL
Mayo Clinic proceedings. 2021;(9):2386-2397
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Abstract
OBJECTIVE To investigate the energy and macronutrient bioaccessibility of almonds in individuals with hyperlipidemia. METHODS In a previously reported randomized crossover trial, men and postmenopausal women with hyperlipidemia incorporated 3 isoenergetic supplements into a National Cholesterol Education Program Step 2 diet for 1 month each between September 20, 2000, and June 27, 2001. Supplements provided consisted of full-dose almonds (73±5 g/d), half-dose almonds (38±3 g/d) plus half-dose muffins, and full-dose muffins (control). Energy and macronutrients, including individual fatty acids, were measured in the dietary supplements and fecal samples using gas chromatography and Association of Official Analytical Chemists methods. Serum was measured for lipids and fatty acids. Bioaccessibility of energy and macronutrients from almond consumption was assessed from dietary intake (7-day food records) and fecal output. RESULTS Almond-related energy bioaccessibility was 78.5%±3.1%, with an average energy loss of 21.2%±3.1% (40.6 kcal/d in the full-dose almond phase). Bioaccessibility of energy and fat from the diet as a whole was significantly less with almond consumption (in both half- and full-dose phases) compared with the control. Bioaccessibility of fat was significantly different between treatment phases (P<.001) and on average lower by 5.1% and 6.3% in the half- and full-dose almond phases, respectively, compared with the control phase. Energy bioaccessibility was significantly different between the treatment phases (P=.02), decreasing by approximately 2% with the inclusion of the full dose of almonds compared with the control. CONCLUSION Energy content of almonds may not be as bioaccessible in individuals with hyperlipidemia as predicted by Atwater factors, as suggested by the increased fat excretion with almond intake compared with the control. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00507520.
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Cholesterotic fibrous histiocytoma: Case report and literature review.
Lukach, AJ, Adams, AK, Werling, RW
Journal of cutaneous pathology. 2021;(7):958-960
Abstract
Cholesterotic fibrous histiocytoma is a particularly rare variant of dermatofibroma that is distinguished histopathologically by the presence of prominent cholesterol deposits within the lesion. We report the case of a 54-year-old male with poorly controlled hyperlipidemia who presented with a firm violaceous papule on the right shin, diagnosed as a cholesterotic fibrous histiocytoma. We also review and summarize the existing literature on this uncommon entity.
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Safety and Efficacy of Pitavastatin in Patients With Impaired Fasting Glucose and Hyperlipidemia: A Randomized, Open-labeled, Multicentered, Phase IV Study.
Lee, HY, Han, KH, Chung, WB, Her, SH, Park, TH, Rha, SW, Choi, SY, Jung, KT, Park, JS, Kim, PJ, et al
Clinical therapeutics. 2020;(10):2036-2048
Abstract
PURPOSE Although the role of high-intensity lipid-lowering therapy in cardiovascular protection has broadened, concerns still exist about new-onset diabetes mellitus (NODM), especially in vulnerable patients. This study aimed to compare the effect of high-dose (4 mg/d) and usual dose (2 mg/d) pitavastatin on glucose metabolism in patients with hyperlipidemia and impaired fasting glucose (IFG). METHODS In this 12-month study, glucose tolerance and lipid-lowering efficacy of high-dose pitavastatin (4 mg [study group]) was compared with that of usual dose pitavastatin (2 mg [control group]) in patients with hyperlipidemia and IFG. The primary end point was the change of glycosylated hemoglobin (HbA1c) after 24 weeks of treatment. The secondary end points were as follows: (1) NODM within 1 year after treatment, (2) change of lipid parameters, (3) changes of adiponectin, and (4) change of blood glucose and insulin levels. FINDINGS Of the total 417 patients screened, 313 patients with hypercholesterolemia and IFG were randomly assigned into groups. The mean (SD) change in HbA1c was 0.06% (0.20%) in the study group and 0.03% (0.22%) in the control group (P = 0.27). Within 1 year, 27 patients (12.3%) developed NODM, including 12 (10.6%) of 113 patients in the study group and 15 (14.2%) of 106 in the control group (P = 0.43). The study group had a significantly higher reduction of total cholesterol and LDL-C levels and a higher increase in apolipoprotein A1/apolipoprotein B ratio (0.68 [0.40] vs 0.51 [0.35], P < 0.01). IMPLICATIONS The high-dose pitavastatin therapy did not aggravate glucose metabolism compared with the usual dose therapy. Moreover, it had a better effect on cholesterol-lowering and apolipoprotein distribution in the patients with hyperlipidemia and IFG.