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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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Fruit and Vegetable Consumption and High-Density Lipoproteins in Overweight or Obese Individuals: A Meta-analysis.
Arnotti, K, Bamber, M
The Journal of cardiovascular nursing. 2021;(1):78-87
Abstract
BACKGROUND Overweight and obesity are associated with low levels of high-density lipoprotein (HDL). The occurrence of cardiovascular disease is strongly predicted by HDL. Increased HDL reduces the risk of cardiovascular disease and stroke. Increased fruit and vegetable consumption (FVC) has been proposed to increase HDL in overweight and obesity; however, research outcomes are inconclusive on the effects of FVC on HDL in this population. OBJECTIVE The purpose of this study was to examine the effect of weight loss FVC interventions on HDL in overweight or obese individuals. METHODS We conducted a meta-analysis using a random-effects model to analyze the results of 6 primary studies. Secondarily, we conducted moderator analyses to explore the effects based on participants, methods, intervention, and source characteristics. RESULTS We found a small standardized mean difference of FVC on HDL (d = 0.18; 95% confidence interval, 0.06-0.29; z = 3.04, P < .01), minimal heterogeneity (Q = 6.10, P = .30, I = 18.05%), and possible publication bias. Moderator analyses indicated that masking of data collectors (Z = 3.73, P = .05) and intention-to-treat analysis (Z = 3.73, P = .05) significantly moderated the overall summary effect. Given that only 1 research team reported masking and intention to treat, these results should be interpreted with caution. CONCLUSIONS There was a small increase in HDL across studies (d = 0.18) in overweight and obese individuals. The effect size may be limited because of the small number of studies included in this meta-analysis. Nonetheless, obese and overweight individuals should be encouraged to increase their FVC to improve HDL and lower cardiovascular risk factors.
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A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids.
Jhun, MA, Mendelson, M, Wilson, R, Gondalia, R, Joehanes, R, Salfati, E, Zhao, X, Braun, KVE, Do, AN, Hedman, ÅK, et al
Nature communications. 2021;(1):3987
Abstract
Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.
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Lipid profile and risk of ovarian tumours: a meta-analysis.
Onwuka, JU, Okekunle, AP, Olutola, OM, Akpa, OM, Feng, R
BMC cancer. 2020;(1):200
Abstract
BACKGROUND Existing data from several reports on the association between lipid profile and ovarian tumour (OT) suggests divergent conclusions. Our aim was to examine whether circulating lipid profile: total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) differed between cases and non-cases of OT. METHODS Electronic repositories; PUBMED, EMBASE and Cochrane library were explored through December 2019 to retrieve published articles for inclusion in the meta-analysis after quality assessment. Heterogeneity was assessed using I2 statistics, the effect of individual studies on the overall effect size was tested using sensitivity analysis and funnel plot was used to evaluate publication bias. RESULTS Twelve studies, involving 1767 OT cases and 229,167 non-cases of OT were included in this meta-analysis and I2 statistics ranged between 97 and 99%. Mean circulating TC (- 16.60 [- 32.43, - 0.77]mg/dL; P = 0.04) and HDL (- 0.25[- 0.43, - 0.08]mmol/L; P = 0.005) were significantly lower among OT cases compared to non-OT cases. CONCLUSION Decreased TC and HDL profiles were observed among subjects with OT in this collection of reports. The implications of TC and HDL in tumour manifestations and growth need to be validated in a large multi-ethnic longitudinal cohort adjusting for relevant confounders.
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High density lipoprotein functionality and cardiovascular events and mortality: A systematic review and meta-analysis.
Soria-Florido, MT, Schröder, H, Grau, M, Fitó, M, Lassale, C
Atherosclerosis. 2020;:36-42
Abstract
BACKGROUND AND AIMS The aim of this systematic review and meta-analysis is to synthesize studies assessing the associations between high-density lipoprotein functionality and risk of cardiovascular disease and mortality. METHODS We searched Medline and Embase for the identification of observational studies meeting the inclusion criteria. This meta-analysis was conducted following the PRISMA statement and was registered in PROSPERO (CRD42017065857). We pooled risk estimates with a random-effect model separately for cardiovascular disease (fatal and non-fatal) and all-cause mortality. RESULTS Out of 29 manuscripts, 20 articles investigated cholesterol efflux capacity (13 prospective and 7 cross-sectional), 10 antioxidant capacity (7 prospective and 3 cross-sectional) and two anti-inflammatory capacity of high-density lipoprotein (1 prospective and 1 cross-sectional). A greater cholesterol efflux capacity was associated with lower risk of cardiovascular disease in 8 studies (RR for 1SD increase: 0.86; 95% CI: 0.76-0.98) and of mortality in 5 studies (RR for 1SD increase: 0,77; 0.60-1.00). Better antioxidant capacity was non-significantly associated with lower cardiovascular disease risk in 2 studies (RR for 1SD increase 0.70; 0.32-1.53) and significantly with mortality in 3 studies (RR for 1SD increase 0.48; 0.28-0.81). High-density lipoprotein anti-inflammatory ability was associated with a lower cardiovascular disease risk in the only prospective study. CONCLUSIONS Greater high-density lipoprotein cholesterol efflux capacity and antioxidant/anti-inflammatory capacities were associated with lower risk of cardiovascular disease. However, the heterogeneity between studies and evidence of publication bias warrants caution and highlights the need for larger prospective studies with standardized assays and specific outcomes.
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Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine.
Onderwater, GLJ, Ligthart, L, Bot, M, Demirkan, A, Fu, J, van der Kallen, CJH, Vijfhuizen, LS, Pool, R, Liu, J, Vanmolkot, FHM, et al
Neurology. 2019;(16):e1899-e1911
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Abstract
OBJECTIVE To identify a plasma metabolomic biomarker signature for migraine. METHODS Plasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a 1H-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g., lipids, fatty acids, and lipoproteins) and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with a random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Next, a global test analysis was performed to identify sets of related metabolites associated with migraine. The Holm procedure was applied to control the family-wise error rate at 5% in single-metabolite and global test analyses. RESULTS Decreases in the level of apolipoprotein A1 (β -0.10; 95% confidence interval [CI] -0.16, -0.05; adjusted p = 0.029) and free cholesterol to total lipid ratio present in small high-density lipoprotein subspecies (HDL) (β -0.10; 95% CI -0.15, -0.05; adjusted p = 0.029) were associated with migraine status. In addition, only in male participants, a decreased level of omega-3 fatty acids (β -0.24; 95% CI -0.36, -0.12; adjusted p = 0.033) was associated with migraine. Global test analysis further supported that HDL traits (but not other lipoproteins) were associated with migraine status. CONCLUSIONS Metabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.
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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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A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials.
de Denus, S, Rouleau, JL, Mann, DL, Huggins, GS, Cappola, TP, Shah, SH, Keleti, J, Zada, YF, Provost, S, Bardhadi, A, et al
The pharmacogenomics journal. 2017;(2):192-200
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We conducted a meta-analysis of pharmacogenomic substudies of three randomized trials conducted in patients with decompensated heart failure (HF) that were led by National Heart Lung and Blood Institute (NHLBI)-funded HF Network to test the hypothesis that candidate genes modulate net fluid loss and weight change in patients with decompensated HF treated with a furosemide-based diuretic regimen. Although none of the genetic variants previously shown to modulate the effects of loop diuretics in healthy individuals were associated with net fluid loss after 72 h of treatment, a set of rare variants in the APOL1 gene, which codes for apolipoprotein L1 (P=0.0005 in the random effects model), was associated with this end point. Moreover, a common variant in the multidrug resistance protein-4 coding gene (ABCC4, rs17268282) was associated with weight loss with furosemide use (P=0.0001). Our results suggest that both common and rare genetic variants modulate the response to a furosemide-based diuretic regimen in patients with decompensated HF.
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Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients.
Keene, D, Price, C, Shun-Shin, MJ, Francis, DP
BMJ (Clinical research ed.). 2014;:g4379
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OBJECTIVE To investigate the effects on cardiovascular outcomes of drug interventions that increase high density lipoprotein levels. DESIGN Meta-analysis. STUDIES REVIEWED Therapeutic benefit of niacin, fibrates, and cholesteryl ester transfer protein (CETP) inhibitors on cardiovascular events (all cause mortality, coronary heart disease mortality, non-fatal myocardial infarction, and stroke). RESULTS 117,411 patients were randomised in a total of 39 trials. All interventions increased the levels of high density lipoprotein cholesterol. No significant effect was seen on all cause mortality for niacin (odds ratio 1.03, 95% confidence interval 0.92 to 1.15, P=0.59), fibrates (0.98, 0.89 to 1.08, P=0.66), or CETP inhibitors (1.16, 0.93 to 1.44, P=0.19); on coronary heart disease mortality for niacin (0.93, 0.76 to 1.12, P=0.44), fibrates (0.92, 0.81 to 1.04, P=0.19), or CETP inhibitors (1.00, 0.80 to 1.24, P=0.99); or on stroke outcomes for niacin (0.96, 0.75 to 1.22, P=0.72), fibrates (1.01, 0.90 to 1.13, P=0.84), or CETP inhibitors (1.14, 0.90 to 1.45, P=0.29). In studies with patients not receiving statins (before the statin era), niacin was associated with a significant reduction in non-fatal myocardial infarction (0.69, 0.56 to 0.85, P=0.0004). However, in studies where statins were already being taken, niacin showed no significant effect (0.96, 0.85 to 1.09, P=0.52). A significant difference was seen between these subgroups (P=0.007). A similar trend relating to non-fatal myocardial infarction was seen with fibrates: without statin treatment (0.78, 0.71 to 0.86, P<0.001) and with all or some patients taking statins (0.83, 0.69 to 1.01, P=0.07); P=0.58 for difference. CONCLUSIONS Neither niacin, fibrates, nor CETP inhibitors, three highly effective agents for increasing high density lipoprotein levels, reduced all cause mortality, coronary heart disease mortality, myocardial infarction, or stroke in patients treated with statins. Although observational studies might suggest a simplistic hypothesis for high density lipoprotein cholesterol, that increasing the levels pharmacologically would generally reduce cardiovascular events, in the current era of widespread use of statins in dyslipidaemia, substantial trials of these three agents do not support this concept.
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Association of baseline high-density lipoprotein levels with restenosis after coronary stenting: a meta-analysis.
He, WJ, Zhou, Y, Liu, JX, Liu, J
Coronary artery disease. 2013;(5):386-91
Abstract
BACKGROUND Previous studies have reported inconsistent results on the association between serum baseline high-density lipoprotein cholesterol (HDL-C) levels and in-stent restenosis (ISR) after coronary stenting. MATERIALS AND METHODS We searched for studies without language restriction in PubMed, Embase, and the Cochrane library before June 2012. Inverse random weighted meta-analysis was carried out using logarithm of the odds ratio of ISR with its SE to assess the strength of association in each study. RESULTS Eight observational studies involving 422 ISR and 1113 non-ISR patients were eligible for our analysis. Overall, there was no association between baseline HDL-C levels and ISR (odds ratio: 1.00, 95% confidence interval: 0.96-1.04). The heterogeneity was not significant between individual studies (P=0.074, I=44.0%) and no publication bias was detected. A sensitivity analysis further confirmed the robustness of results. A similar association was detected in the subgroups with bare metal stent and drug-eluting stent implantation. CONCLUSION Our meta-analysis suggests that serum baseline HDL-C levels are not associated with ISR.