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Effect of JAK inhibitors on high- and low-density lipoprotein in patients with rheumatoid arthritis: a systematic review and network meta-analysis.
Li, N, Gou, ZP, Du, SQ, Zhu, XH, Lin, H, Liang, XF, Wang, YS, Feng, P
Clinical rheumatology. 2022;(3):677-688
Abstract
OBJECTIVES Janus kinase (JAK) inhibitors are a new class of medication for treatment of rheumatoid arthritis (RA), and such inhibitors alter levels of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in RA patients. However, the extent of such changes has not been systematically reviewed. METHOD A systematic review and network meta-analysis was performed on randomized trials in RA patients in response to JAKi identified from Pubmed, Medline, Embase, and Cochrane Controlled Trials Register. The primary outcome was mean change of HDL-C and LDL-C from baseline. Mean treatment differences and the rank of the effect of various JAKi on HDL-C and LDL-C were estimated. RESULTS Based on data from 18 unique studies involving five approved JAK inhibitors and 6697 RA patients (JAKi = 3341, placebo = 3356), such inhibitors led to a mean increase of 8.11 mg/dl (95% CI 6.65-9.58, I2 = 82%) in HDL levels from baseline, and a mean increase of 11.37 mg/dl (95% CI 7.84-14.91, I2 = 88%) in LDL levels from baseline. Cardiovascular disease risk did not differ significantly between patients who received JAK inhibitors or those who received placebo or active agents. CONCLUSIONS Our analysis suggests that, at their recommended doses, all five JAK inhibitors lead to an increase in HDL and LDL levels in RA patients. Further long-term research is required to extend these results and understand whether changes in lipid levels in RA patients can affect cardiovascular risk. Key Points • This is the first systematic review and NMA examining the effect of all five clinically approved JAK inhibitors on lipid levels in RA patients. • Recommended doses of JAK inhibitors used for the treatment of RA patients can induce a significant increase in HDL and LDL levels. • Indirect pairwise comparisons suggest that only upadacitinib and peficitinib have significantly different ability to induce LDL change in RA patients.
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The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Jamialahmadi, T, Baratzadeh, F, Reiner, Ž, Simental-Mendía, LE, Xu, S, Susekov, AV, Santos, RD, Sahebkar, A
Mediators of inflammation. 2021;:9661752
Abstract
BACKGROUND Elevated plasma low-density lipoprotein cholesterol (LDL-C) is the main risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the drugs of choice for decreasing LDL-C and are used for the prevention and management of ASCVD. Guidelines recommend that subjects with high and very high ASCVD risk should be treated with high-intensity statins or a combination of high-intensity statins and ezetimibe. The lipophilicity or hydrophilicity (solubility) of statins is considered to be important for at least some of their LDL-C lowering independent pleiotropic effects. Oxidative modification of LDL (ox-LDL) is considered to be the most important atherogenic modification of LDL and is supposed to play a crucial role in atherogenesis and ASCVD outcomes. OBJECTIVE The aim of this systematic review and meta-analysis was to find out what are the effects of statin intensity, lipophilicity, and combination of statins plus ezetimibe on ox-LDL. METHODS PubMed, Scopus, Embase, and Web of Science were searched from inception to February 5, 2021, for randomized controlled trials (RCTs). Two independent and blinded authors evaluated eligibility by screening the titles and abstracts of the studies. Risk of bias in the studies included in this meta-analysis was evaluated according to the Cochrane instructions. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. Evaluation of funnel plot, Begg's rank correlation, and Egger's weighted regression tests were used to assess the presence of publication bias. RESULTS Among the 1427 published studies identified by a systematic databases search, 20 RCTs were finally included in the systematic review and meta-analysis. A total of 1874 patients are included in this meta-analysis. This meta-analysis suggests that high-intensity statin treatment is associated with a significant decrease in circulating concentrations of ox-LDL when compared with low-to-moderate treatment (SMD: -0.675, 95% CI: -0.994, -0.357, p < 0.001; I 2: 55.93%). There was no difference concerning ox-LDL concentration between treatments with hydrophilic and lipophilic statins (SMD: -0.129, 95% CI: -0.330, -0.071, p = 0.206; I 2: 45.3%), but there was a significant reduction in circulating concentrations of ox-LDL associated with statin plus ezetimibe combination therapy when compared with statin monotherapy (SMD: -0.220, 95% CI: -0.369, -0.071, p = 0.004; I 2: 0%). CONCLUSION High-dose statin or combination of statins with ezetmibe reduces plasma ox-LDL in comparison low-to-moderate intensity statin therapy alone. Statin lipophilicity is not associated with reduction in ox-LDL plasma concentrations.
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3.
The Effect of Bariatric Surgery on Circulating Levels of Oxidized Low-Density Lipoproteins Is Apparently Independent of Changes in Body Mass Index: A Systematic Review and Meta-Analysis.
Jamialahmadi, T, Reiner, Ž, Alidadi, M, Kroh, M, Cardenia, V, Xu, S, Al-Rasadi, K, Santos, RD, Sahebkar, A
Oxidative medicine and cellular longevity. 2021;:4136071
Abstract
BACKGROUND Obesity is related to dyslipidemia and increased circulating oxidated LDL (ox-LDL) concentrations that may predispose to atherosclerosis. Bariatric surgery may lower the risk of cardiovascular mortality. Elevated plasma ox-LDL has been associated with atherogenesis and atherosclerotic cardiovascular disease (ASCVD) events. The aim of this meta-analysis was to investigate the impact of bariatric surgery on proatherogenic circulating ox-LDL levels in patients with severe obesity. METHODS Four databases were systematically searched from inception to May 1, 2021. Also, to clarify the heterogeneity of studies with regard to treatment duration, research design, and the demographic features, a random-effects model and the generic inverse variance weighting approach were utilized. To determine the association with the estimated effect size, a random-effect meta-regression approach was performed. Finally, a meta-regression analysis was conducted to explore the influence of, respectively, baseline and changes in body mass index (BMI), baseline ox-LDL, and postsurgery follow-up period with the estimated effect size of surgery on ox-LDL levels. RESULTS Meta-analysis of 11 studies including 470 subjects showed a significant decline in circulating ox-LDL following bariatric surgery (SMD: -0.971, 95% CI: -1.317, -0.626, p < 0.001, I 2: 89.43%). The results of meta-regression did not show any significant association between the changes in ox-LDL after bariatric surgery and baseline BMI, duration of follow-up or baseline ox-LDL values. However, there was a significant association between ox-LDL alteration and percentage of BMI change. CONCLUSION Bariatric surgery in patients who had severe obesity causes a decrease of circulating ox-LDL that was apparently dependent in BMI changes.
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4.
Serum lipids and risk of atherosclerosis in xanthelasma palpebrarum: A systematic review and meta-analysis.
Chang, HC, Sung, CW, Lin, MH
Journal of the American Academy of Dermatology. 2020;(3):596-605
Abstract
BACKGROUND The association between dyslipidemia and xanthelasma palpebrarum (XP) remains controversial, and no definite evidence has indicated atherosclerosis risk in patients with XP. OBJECTIVE The present study was a systematic review and meta-analysis to elucidate the association of serum lipid profiles and risk of atherosclerotic diseases with XP. METHODS We systematically searched for the eligible comparative studies published before April 15, 2019, in the databases of PubMed, Web of Science, Embase, and Cochrane Library. A random-effects model was used to calculate the standard mean difference with 95% confidence interval for each pooled estimate. RESULTS The qualitative analyses included 15 case-control studies with 854 patients with XP. Compared with the controls, the patients with XP had significantly higher serum levels of total cholesterol and low-density lipoproteins, significantly higher apolipoprotein B levels, and relatively lower apolipoprotein A1 levels, and the carotid intima-media thickness was significantly higher. CONCLUSION Patients with XP had significantly higher serum levels of atherogenic low-density lipoproteins and bore significantly higher risk of atherosclerosis than the controls. Careful monitoring and targeted intervention for prevention of cardiovascular diseases is essential for these patients.
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5.
Effect of Strength Training on Lipid and Inflammatory Outcomes: Systematic Review With Meta-Analysis and Meta-Regression.
Costa, RR, Buttelli, ACK, Vieira, AF, Coconcelli, L, Magalhães, RL, Delevatti, RS, Kruel, LFM
Journal of physical activity & health. 2019;(6):477-491
Abstract
Background: The aim of this study was to perform a systematic review with meta-analysis and meta-regressions evaluating the effects of isolated strength training (ST), compared with a control group, on total cholesterol (TC), triglycerides (TG), low-density (LDL), high-density lipoprotein (HDL), C-reactive protein (CRP), and adiponectin of adults. Methods: Embase, PubMed, Cochrane, and Scopus data sources were searched up to May 2017. Clinical trials that compared ST with a control group of adults older than 18 years, which evaluated blood TC, TG, LDL, HDL, CRP, or adiponectin as an outcome were included. Random effect was used and the effect size (ES) was calculated by using the standardized mean difference with a 95% confidence interval. Results: ST promotes a reduction in TC (ES: -0.399; P < .001), TG (ES: -0.204; P = .002), LDL (ES: -0.451; P < .001), and CRP (ES: -0.542; P = .01) levels. In addition, ST is associated to an increase in HDL (ES: 0.363; P < .001) and adiponectin concentrations (ES: 1.105; P = .01). Conclusion: ST promotes decreases in TC, TG, LDL, and CRP levels and increases HDL and adiponectin concentrations. Thus, progressive ST could be a potential therapeutic option for improving abnormalities in lipid and inflammatory outcomes in adults.
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Favorable effects of hydroxychloroquine on serum low density lipid in patients with systemic lupus erythematosus: A systematic review and meta-analysis.
Babary, H, Liu, X, Ayatollahi, Y, Chen, XP, Doo, L, Uppaluru, LK, Kwak, MK, Kulaga, C, Modjinou, D, Olech, E, et al
International journal of rheumatic diseases. 2018;(1):84-92
Abstract
AIMS: Hydroxychloroquine (HCQ) has shown to have significant immunomodulatory effects in the treatment of systemic lupus erythematosus (SLE). Current studies show favorable effects of HCQ on traditional cardiac risk factors in patients with SLE. This review examined the effects of HCQ on serum low-density lipoprotein (LDL) level in patients with SLE. METHODS A systematic search of seven major literature search databases from their inception until 3 April, 2017 identified nine studies. Random-effects pooled mean difference with corresponding 95% confidence intervals (CI) were estimated. Heterogeneity was measured by I2 . Publication bias was assessed by visual inspection of funnel plots. Sensitivity analysis examined whether HCQ effect on serum total cholesterol level was similar to the main analysis. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the overall quality of evidence. RESULTS Pooled study participants were 559 patients from eight observation studies (two before-after studies; six case-control studies) examining the effects of HCQ on serum LDL. Pooled study participants' characteristics were as follows: mean age 45.719, female 95.262%, and prednisone use 58.366%. HCQ reduced mean LDL levels by 24.397 mg/dL (95% CI 8.921-39.872; P = 0.002). The number of studies identifying statin use was too few to perform meta-regression analysis of statin use. Heterogeneity was extensive (I2 = 94.739%). Symmetrical funnel plot visualized no evidence of publication bias. CONCLUSION HCQ was associated with serum LDL level reduction by mean 24.397 mg/dL in patients with SLE. Future prospective studies are need to fully characterize the treatment effect.