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Rice bran oil could favorably ameliorate atherogenicity and insulin resistance indices among men with coronary artery disease: post hoc analysis of a randomized controlled trial.
Mahdavi-Roshan, M, Salari, A, Vakilpour, A, Savar Rakhsh, A, Ghorbani, Z
Lipids in health and disease. 2021;(1):153
Abstract
BACKGROUND Despite recent advances in recognizing more reliable indicators to estimate the coronary artery disease (CAD) patients' response to treatment and prognosis, less attention has been paid to evaluating them in clinical trials. Hence, the present research was conducted to study the impact of rice bran oil (RBO) versus sunflower oil (SFO) on various atherogenicity and insulin resistance markers. METHODS In the present 8-week randomized controlled trial, 40 CAD men with an average age of 56 years were allocated randomly into the intervention or control group to use RBO or SFO (30 g/day) plus a standardized dietary plan. As a further analysis, eight atherosclerosis-related indices were calculated before and after the study. RESULTS Analysis of covariance test in which potential confounders and baseline levels were considered, indicated that using RBO compared to SFO reduced Castelli's risk index I and II (adjusted means:3.29, 1.52 vs. 4.61, 2.20, respectively), atherogenic coefficient (2.29 vs. 3.61), lipoprotein combine index (6.54 vs. 17.53), and cholesterol index (0.46 vs. 1.20) after the trial (P-value ≤ 0.002). Also, the RBO group yielded significantly lower triglyceride glucose index (8.73 vs. 9.13) (P-value = 0.010). Further, marginally significant amelioration in triglyceride/HDL ratio and atherogenic index of plasma (1.48 and 0.13 vs. 1.86 and 0.24 respectively) were noted (P-value = 0.07). Spearman correlation analysis detected significant positive correlations between alterations in TNF-α serum levels (ng/L) and the majority of evaluated indices (P-value < 0.05). CONCLUSION Taken together, incorporating 30 g of RBO into the patient's usual diet appeared effective in ameliorating atherogenicity and insulin resistance indicators among men with CAD, probably in relation to its anti-inflammatory properties. TRIAL REGISTRATION The protocol of the current trial was retrospectively recorded in the Iranian clinical trial registration system (IRCT) with the registration number of IRCT20190313043045N1 (URL: https://en.irct.ir/trial/38346 ; Registration date: 2019-04-27).
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The Beneficial Effects of Astaxanthin on Glucose Metabolism and Modified Low-Density Lipoprotein in Healthy Volunteers and Subjects with Prediabetes.
Urakaze, M, Kobashi, C, Satou, Y, Shigeta, K, Toshima, M, Takagi, M, Takahashi, J, Nishida, H
Nutrients. 2021;(12)
Abstract
UNLABELLED Astaxanthin (ASTX) is an antioxidant agent. Recently, its use has been focused on the prevention of diabetes and atherosclerosis. We examined the effects of astaxanthin supplementation for 12 weeks on glucose metabolism, glycemic control, insulin sensitivity, lipid profiles and anthropometric indices in healthy volunteers including subjects with prediabetes with a randomized, placebo-controlled trial. METHODS We enrolled 53 subjects who met our inclusion criteria and administered them with 12 mg astaxanthin or a placebo once daily for 12 weeks. Subsequently, their HbA1c levels, lipid profiles and biochemical parameters were determined. The participants also underwent a 75 g oral glucose tolerance test (OGTT), vascular endothelial function test and measurement of the visceral fat area. RESULTS After astaxanthin supplementation for 12 weeks, glucose levels after 120 min in a 75 g OGTT significantly decreased compared to those before supplementation. Furthermore, the levels of HbA1c (5.64 ± 0.33 vs. 5.57 ± 0.39%, p < 0.05), apo E (4.43 ± 1.29 vs. 4.13 ± 1.24 mg/dL, p < 0.05) and malondialdehyde-modified low-density lipoprotein (87.3 ± 28.6 vs. 76.3 ± 24.6 U/L, p < 0.05) were also reduced, whereas total cholesterol (TC), triglyceride (TG) and high-density lipoprotein-C (HDL-C) levels were unaltered. The Matuda index, which is one of the parameters of insulin resistance, was improved in the ASTX group compared to that before supplementation. CONCLUSIONS our results suggest that ASTX may have preventive effects against diabetes and atherosclerosis and may be a novel complementary treatment option for the prevention of diabetes in healthy volunteers, including subjects with prediabetes, without adverse effects.
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Ertugliflozin and Slope of Chronic eGFR: Prespecified Analyses from the Randomized VERTIS CV Trial.
Cherney, DZI, Cosentino, F, Dagogo-Jack, S, McGuire, DK, Pratley, R, Frederich, R, Maldonado, M, Liu, CC, Liu, J, Pong, A, et al
Clinical journal of the American Society of Nephrology : CJASN. 2021;(9):1345-1354
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BACKGROUND AND OBJECTIVES A reduction in the rate of eGFR decline, with preservation of ≥0.75 ml/min per 1.73 m2 per year, has been proposed as a surrogate for kidney disease progression. We report results from prespecified analyses assessing effects of ertugliflozin versus placebo on eGFR slope from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease were randomized to placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg (1:1:1). The analyses compared the effect of ertugliflozin (pooled doses, n=5499) versus placebo (n=2747) on eGFR slope per week and per year by random coefficient models. Study periods (weeks 0-6 and weeks 6-52) and total and chronic slopes (week 0 or week 6 to weeks 104, 156, 208, and 260) were modeled separately and by baseline kidney status. RESULTS In the overall population, for weeks 0-6, the least squares mean eGFR slopes (ml/min per 1.73 m2 per week [95% confidence interval (95% CI)]) were -0.07 (-0.16 to 0.03) and -0.54 (-0.61 to -0.48) for the placebo and ertugliflozin groups, respectively; the difference was -0.47 (-0.59 to -0.36). During weeks 6-52, least squares mean eGFR slopes (ml/min per 1.73 m2 per year [95% CI]) were -0.12 (-0.70 to 0.46) and 1.62 (1.21 to 2.02) for the placebo and ertugliflozin groups, respectively; the difference was 1.74 (1.03 to 2.45). For weeks 6-156, least squares mean eGFR slopes (ml/min per 1.73 m2 per year [95% CI]) were -1.51 (-1.70 to -1.32) and -0.32 (-0.45 to -0.19) for the placebo and ertugliflozin groups, respectively; the difference was 1.19 (0.95 to 1.42). During weeks 0-156, the placebo-adjusted difference in least squares mean slope was 1.06 (0.85 to 1.27). These findings were consistent by baseline kidney status. CONCLUSIONS Ertugliflozin has a favorable placebo-adjusted eGFR slope >0.75 ml/min per 1.73 m2 per year, documenting the kidney function preservation underlying the clinical benefits of ertugliflozin on kidney disease progression in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER US National Library of Medicine, ClinicalTrials.gov NCT01986881. Date of trial registration: November 13, 2013.
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Modulation of Cardiometabolic Disease Markers by Type I Interferon Inhibition in Systemic Lupus Erythematosus.
Casey, KA, Smith, MA, Sinibaldi, D, Seto, NL, Playford, MP, Wang, X, Carlucci, PM, Wang, L, Illei, G, Yu, B, et al
Arthritis & rheumatology (Hoboken, N.J.). 2021;(3):459-471
Abstract
OBJECTIVE Neutrophil dysregulation and the type I interferon (IFN) axis have been proposed to contribute to premature cardiovascular disease, a leading cause of mortality in patients with systemic lupus erythematosus (SLE). In the present study, we evaluated the ability of anifrolumab, a type I IFN receptor-blocking antibody, to reduce neutrophil extracellular trap (NET) formation and modulate cardiometabolic disease markers in comparison to placebo. METHODS Study subjects comprised patients with moderate-to-severe SLE who were enrolled in phase IIb of the MUSE trial (A Phase II, Randomized Study to Evaluate the Efficacy and Safety of MEDI-546 in Subjects with Systemic Lupus Erythematosus), with healthy individuals as controls. Blood samples were collected from SLE patients (n = 305) and healthy controls (n = 10-20) before the initiation of treatment (baseline) and from SLE patients after they had been treated with 300 mg of anifrolumab (n = 99) or placebo (n = 102). Baseline IFN gene signature test status was determined, and the IFN gene signature (21-gene panel) was monitored over time. Serum proteins were measured by multiplex immunoassay or ultrasensitive Simoa assay. NET complexes, cholesterol efflux capacity (CEC), and glycoprotein acetylation (GlycA) and other lipid parameters were assessed in plasma. RESULTS Formation of NET complexes and levels of tumor necrosis factor (TNF) and interleukin-10 (IL-10) were correlated with extent of type I IFN pathway activity. NET complexes and IL-10 levels were up-regulated in SLE patients compared to healthy controls (P < 0.008). The cardiometabolic disease markers CEC and GlycA were also found to be dysregulated in patients with SLE (P < 0.001 versus healthy controls). Type I IFN receptor inhibition with anifrolumab significantly reduced NET complexes and GlycA and improved CEC compared to baseline (P < 0.05) whereas no improvements were seen with placebo. Levels of TNF and IL-10 were reduced with anifrolumab compared to placebo (P < 0.05). CONCLUSION These data support a key role for type I IFNs in modulating factors contributing to SLE vasculopathy and suggest that inhibition of this pathway could decrease cardiovascular risk in individuals with SLE.
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Low-Dose Methotrexate for the Prevention of Atherosclerotic Events.
Ridker, PM, Everett, BM, Pradhan, A, MacFadyen, JG, Solomon, DH, Zaharris, E, Mam, V, Hasan, A, Rosenberg, Y, Iturriaga, E, et al
The New England journal of medicine. 2019;(8):752-762
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BACKGROUND Inflammation is causally related to atherothrombosis. Treatment with canakinumab, a monoclonal antibody that inhibits inflammation by neutralizing interleukin-1β, resulted in a lower rate of cardiovascular events than placebo in a previous randomized trial. We sought to determine whether an alternative approach to inflammation inhibition with low-dose methotrexate might provide similar benefit. METHODS We conducted a randomized, double-blind trial of low-dose methotrexate (at a target dose of 15 to 20 mg weekly) or matching placebo in 4786 patients with previous myocardial infarction or multivessel coronary disease who additionally had either type 2 diabetes or the metabolic syndrome. All participants received 1 mg of folate daily. The primary end point at the onset of the trial was a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Near the conclusion of the trial, but before unblinding, hospitalization for unstable angina that led to urgent revascularization was added to the primary end point. RESULTS The trial was stopped after a median follow-up of 2.3 years. Methotrexate did not result in lower interleukin-1β, interleukin-6, or C-reactive protein levels than placebo. The final primary end point occurred in 201 patients in the methotrexate group and in 207 in the placebo group (incidence rate, 4.13 vs. 4.31 per 100 person-years; hazard ratio, 0.96; 95% confidence interval [CI], 0.79 to 1.16). The original primary end point occurred in 170 patients in the methotrexate group and in 167 in the placebo group (incidence rate, 3.46 vs. 3.43 per 100 person-years; hazard ratio, 1.01; 95% CI, 0.82 to 1.25). Methotrexate was associated with elevations in liver-enzyme levels, reductions in leukocyte counts and hematocrit levels, and a higher incidence of non-basal-cell skin cancers than placebo. CONCLUSIONS Among patients with stable atherosclerosis, low-dose methotrexate did not reduce levels of interleukin-1β, interleukin-6, or C-reactive protein and did not result in fewer cardiovascular events than placebo. (Funded by the National Heart, Lung, and Blood Institute; CIRT ClinicalTrials.gov number, NCT01594333.).
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Comparative effects of 2.5mg levamlodipine and 5mg amlodipine on vascular endothelial function and atherosclerosis.
Lu, Y, Yin, J, Wu, X, Fan, Y, Liu, F
Pakistan journal of pharmaceutical sciences. 2019;(5(Special)):2433-2436
Abstract
This study was designed to compare the efficacy of two different racemic antihypertensive drugs on elderly patients with hypertension and their effects on vascular endothelial function and atherosclerosis. A total of 84 elderly hypertensive patients were randomly divided into control and treatment group with 42 patients in each group. The control group was treated with 2.5mg levamlodipine while the treatment group was given 5mg amlodipine. Total effective rate of the treatment group was 90.5%, higher than the control group, that was 71.4% (P<0.05). The time for recovery of related indicators like blood pressure, the total duration of medication were significantly (P<0.05) shorter in the treatment group. Only 1 case of adverse drug reaction was found in the treatment group while 6 cases in control group. Compared to the control group, the treatment group had massive improvement in fingertip pulse volume, flow-mediated dilation of the brachial arteries and endothelin-1 level, carotid intima-media thickness, plaque length & thickness, and blood pressure after the administration. The rate of satisfaction with the in treatment group was 95.3%, higher than that the control group, which was 78.6%. The study concluded that in elderly patients with hypertension, the treatment with 5mg amlodipine enhanced curative effect, fully improved endothelial function & arteriosclerosis and reduced adverse reactions thereby shortening treatment time.
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Effect of rosuvastatin and eicosapentaenoic acid on neoatherosclerosis: the LINK-IT Trial.
Kuroda, K, Otake, H, Shinohara, M, Kuroda, M, Tsuda, S, Toba, T, Nagano, Y, Toh, R, Ishida, T, Shinke, T, et al
EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2019;(12):e1099-e1106
Abstract
AIMS: We aimed to assess the effect of 10 mg/day of rosuvastatin plus eicosapentaenoic acid (EPA) versus 2.5 mg/day of rosuvastatin on the extent of neoatherosclerosis using optical coherence tomography (OCT). METHODS AND RESULTS We randomly assigned 50 patients with non-obstructive neoatherosclerotic plaques detected on OCT to receive either rosuvastatin 10 mg/day and EPA 1,800 mg/day (intensive therapy group) or rosuvastatin 2.5 mg (standard therapy group). Follow-up OCT was performed one year later to evaluate serial changes in neoatherosclerosis. The serum low-density lipoprotein cholesterol (LDL-C) level decreased significantly from baseline to 12-month follow-up in the intensive therapy group (89 mg/dL to 70 mg/dL; p<0.001), while no change occurred in the standard therapy group. Lipid index change and percent changes in macrophage grade were significantly lower in the intensive therapy group than in the standard therapy group (-53.6 vs 310.1, p=0.001; -37.0% vs 35.3%, p<0.001; respectively). Percent changes in lipid index and macrophage grade were positively correlated with the changes in serum LDL-C and C-reactive protein levels, and negatively correlated with the change in serum EPA/arachidonic acid and 18-hydroxyeicosapentaenoic acid (EPA bioactive metabolite) level. CONCLUSIONS Compared with rosuvastatin 2.5 mg/day, rosuvastatin 10 mg/day and EPA 1,800 mg/day significantly stabilised non-obstructive neoatherosclerotic plaques. CLINICAL TRIAL REGISTRATION UMIN ID UMIN000012576. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014711.
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Effects of Endurance and Endurance-Strength Training on Endothelial Function in Women with Obesity: A Randomized Trial.
Ratajczak, M, Skrypnik, D, Bogdański, P, Mądry, E, Walkowiak, J, Szulińska, M, Maciaszek, J, Kręgielska-Narożna, M, Karolkiewicz, J
International journal of environmental research and public health. 2019;(21)
Abstract
Some investigations have demonstrated that a combined endurance-strength training is the most effective in the treatment of obesity. The aim of the research was to access how different trainings influence: endothelial function, lipid metabolism, and risk of atherosclerosis in women with obesity. In a randomized trial, 39 obese women aged 28-62 completed endurance (n = 22, 60-80% HRmax) or combined training (n = 17, 20 minutes of strength exercises, 50-60% 1RM and 25 minutes of endurance training, 60-80% HRmax). Before and after the intervention vascular endothelial function (endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), thiobarbituric acid reactive substances (TBARS), blood total antioxidant capacity (TAC)), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides and C-reactive protein (CRP)as well as visceral adiposity index (VAI), total-body skeletal muscle mass and atherogenic index of plasma (AIP) were determined. After the trainings, in both groups total cholesterol and total-body skeletal muscle mass increased (p < 0.05). In the group undergoing combined training, lower (p < 0.05) VAI, AIP, CRP and LDL-C were noted. In the group undergoing endurance training TBARS concentration decreased (p < 0.01), while the HDL-C (p < 0.01) concentration as well as eNOS (p < 0.05) activity increased. No significant differences between groups were found, either before or after the programs. Both training programs led to the improvement of lipid metabolism, but only endurance training alone favorably changed indicators of endothelial functions in women with obesity.
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Icosapent ethyl reduces atherogenic markers in high-risk statin-treated patients with stage 3 chronic kidney disease and high triglycerides.
Vijayaraghavan, K, Szerlip, HM, Ballantyne, CM, Bays, HE, Philip, S, Doyle, RT, Juliano, RA, Granowitz, C
Postgraduate medicine. 2019;(6):390-396
Abstract
Objective: Patients with chronic kidney disease (CKD) have increased cardiovascular disease (CVD) risk, likely driven by atherogenic and inflammatory markers beyond low-density lipoprotein cholesterol (LDL-C). The objective of this hypothesis-generating post hoc subgroup analysis was to explore the effects of icosapent ethyl at 2 or 4 g/day (prescription pure ethyl ester of the omega-3 fatty acid eicosapentaenoic acid [EPA]) on atherogenic lipid, apolipoprotein, inflammatory parameters (high-sensitivity C-reactive protein [hsCRP], lipoprotein-associated phospholipase A2 [Lp-PLA2]), and oxidative parameters (oxidized-LDL [ox-LDL]) in statin-treated patients from ANCHOR with stage 3 CKD.Methods: The 12-week ANCHOR study evaluated icosapent ethyl in 702 statin-treated patients at increased CVD risk with triglycerides (TG) 200-499 mg/dL despite controlled LDL-C (40-99 mg/dL). This post-hoc analysis included patients from ANCHOR with stage 3 CKD (estimated glomerular filtration rate [eGFR] ≤60 mL/min/1.73 m2 for ≥3 months) randomized to icosapent ethyl 4 g/day (n = 19), 2 g/day (n = 30), or placebo (n = 36).Results: At the prescription dose of 4 g/day, icosapent ethyl significantly reduced TG (-16.9%; P = 0.0074) and other potentially atherogenic lipids/lipoproteins, ox-LDL, hsCRP, and Lp-PLA2, and increased plasma and red blood cell EPA levels (+879% and +579%, respectively; both P < 0.0001) versus placebo. Icosapent ethyl did not significantly alter eGFR or serum creatinine. Safety and tolerability were similar to placebo.Conclusions: In patients with stage 3 CKD at high CVD risk with persistent high TG despite statins, icosapent ethyl 4 g/day reduced potentially atherogenic and other cardiovascular risk factors without raising LDL-C, with safety similar to placebo. These findings suggest prospective investigation may be warranted.
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The Effect of Health Education by Pharmacists on 10-Year Atherosclerotic Cardiovascular Disease Risk: A Cluster-Randomized Control Study in a Low Socioeconomic Status Javanese Population.
Suhadi, R, Virginia, DM, Setiawan, CH
Journal of primary care & community health. 2018;:2150132718773674
Abstract
BACKGROUND Evidence from previous studies demonstrates that lifestyle modification reduces the incidence and complications of atherosclerotic cardiovascular disease. The study aimed to investigate the effect of a lifestyle intervention provided by pharmacists on the 10-year atherosclerotic cardiovascular disease (ASCVD) risk and quality of life (QoL) in a low socioeconomic status Javanese population. METHODS This research was a cluster-randomized controlled study of 1-year duration, conducted in a lower social economic community in the Sleman District of Yogyakarta, Indonesia. The eligible subjects were dichotomized into 2 groups: 40 to 55 years (n = 61 vs 65) and 56 to 70 years (n = 21 vs 43) for intervention and control subjects, respectively. The ASCVD score and risk factors within the age-based groups were analyzed using T test/Mann-Whitney test for continuous data or chi-square test for categorical data. RESULTS The intervention and control subjects had similar baseline characteristics ( P > .05), including the ASCVD risk with the low- and high-risk classification for younger and elder subjects, respectively. At final follow-up, the younger intervention subjects had lower 10-year ASCVD risk ( P = .001), higher high-density lipoprotein cholesterol ( P = .02), smoking status ( P = .001), persistence rate ( P = .03), and QoL value for the physical and social function domains ( P < .05) than the control subjects, whereas the elder intervention subjects only had better ASCVD risk score than controls ( P = .03). Smoking interacting with intervention was the most influential variable on ASCVD risk in logistic regression analysis. CONCLUSION The study demonstrates that the health education by the pharmacists produce significant outcomes of the ASCVD risk, smoking status, and QoL of physical and social function particularly in the younger group.