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Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein-Enriched Serum in Rheumatoid Arthritis.

ABSTRACT: OBJECTIVE:Patients with rheumatoid arthritis (RA) have an increased risk of coronary heart disease (CHD). Some RA therapies may modify this risk, but the underlying mechanisms are unclear. The cholesterol efflux capacity of high-density lipoprotein (HDL) is associated with a reduced CHD risk in non-RA populations; however, inflammation may impair the function of HDL. The aim of this study was to evaluate whether reduced inflammation resulting from treatment with methotrexate (MTX), adalimumab (ADA), or tocilizumab (TCZ) would increase the net cholesterol efflux capacity of HDL in patients with RA. METHODS:A longitudinal multicenter study repository (Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository) provided clinical information for and serum samples from 70 patients with RA before and 6 months after starting treatment with a new drug (MTX [n?=?23], ADA [n?=?22], or TCZ [n?=?25]). Disease activity was measured using the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). The net cholesterol efflux capacity was measured in paired serum samples using THP-1 macrophages, and total cellular cholesterol was measured by fluorometric assay. RESULTS:The DAS28-ESR decreased with all treatments (P?

SUBMITTER: Ormseth MJ

PROVIDER: S-EPMC5001900 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein-Enriched Serum in Rheumatoid Arthritis.

Ormseth Michelle J MJ Yancey Patricia G PG Solus Joseph F JF Bridges S Louis SL Curtis Jeffrey R JR Linton MacRae F MF Fazio Sergio S Davies Sean S SS Roberts L Jackson LJ Vickers Kasey C KC Kon Valentina V Michael Stein C C

Arthritis & rheumatology (Hoboken, N.J.) 20160901 9

<h4>Objective</h4>Patients with rheumatoid arthritis (RA) have an increased risk of coronary heart disease (CHD). Some RA therapies may modify this risk, but the underlying mechanisms are unclear. The cholesterol efflux capacity of high-density lipoprotein (HDL) is associated with a reduced CHD risk in non-RA populations; however, inflammation may impair the function of HDL. The aim of this study was to evaluate whether reduced inflammation resulting from treatment with methotrexate (MTX), adali ...[more]

PMID: 26991245

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Project description:High-density lipoprotein (HDL) may provide cardiovascular protection by promoting reverse cholesterol transport from macrophages. We hypothesized that the capacity of HDL to accept cholesterol from macrophages would serve as a predictor of atherosclerotic burden.We measured cholesterol efflux capacity in 203 healthy volunteers who underwent assessment of carotid artery intima-media thickness, 442 patients with angiographically confirmed coronary artery disease, and 351 patients without such angiographically confirmed disease. We quantified efflux capacity by using a validated ex vivo system that involved incubation of macrophages with apolipoprotein B-depleted serum from the study participants.The levels of HDL cholesterol and apolipoprotein A-I were significant determinants of cholesterol efflux capacity but accounted for less than 40% of the observed variation. An inverse relationship was noted between efflux capacity and carotid intima-media thickness both before and after adjustment for the HDL cholesterol level. Furthermore, efflux capacity was a strong inverse predictor of coronary disease status (adjusted odds ratio for coronary disease per 1-SD increase in efflux capacity, 0.70; 95% confidence interval [CI], 0.59 to 0.83; P<0.001). This relationship was attenuated, but remained significant, after additional adjustment for the HDL cholesterol level (odds ratio per 1-SD increase, 0.75; 95% CI, 0.63 to 0.90; P=0.002) or apolipoprotein A-I level (odds ratio per 1-SD increase, 0.74; 95% CI, 0.61 to 0.89; P=0.002). Additional studies showed enhanced efflux capacity in patients with the metabolic syndrome and low HDL cholesterol levels who were treated with pioglitazone, but not in patients with hypercholesterolemia who were treated with statins.Cholesterol efflux capacity from macrophages, a metric of HDL function, has a strong inverse association with both carotid intima-media thickness and the likelihood of angiographic coronary artery disease, independently of the HDL cholesterol level. (Funded by the National Heart, Lung, and Blood Institute and others.).

Project description:BackgroundPoor cholesterol efflux capacity (CEC) has been proposed to be an independent risk factor for cardiovascular diseases. However, current evidence is inconsistent, especially in rheumatoid arthritis (RA) patients. This meta-analysis aims to identify whether CEC is impaired or altered by drug therapy in RA.MethodsThe PubMed/MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov databases were browsed to identify studies on CEC in RA patients. The searches mainly focused on studies in human subjects that were published before November 14, 2020, without any language restrictions. The effect size was pooled by the standardized mean differences and mean differences (SMD & MD) as well as the corresponding 95% confidence intervals (CIs) in a random or fixed effect model. Heterogeneity across the studies was tested using Cochran's Q test and I2 statistic. Newcastle-Ottawa Scale and the Downs and Black scale (D&B) were applied to evaluate the quality of included studies. The GRADE-system with its 4-grade evidence scale was used to assess the quality of evidence.ResultsA total of 11 eligible articles, including 6 observational and 5 interventional studies, were retrieved. The pooled results showed that in patients with RA, CEC was not significantly different than in healthy controls (SMD: -0.34, 95% CI: - 0.83 to 0.14), whereas the plasma HDL-C levels was significantly lower (MD: -3.91, 95% CI: - 7.15 to - 0.68). Furthermore, in the before-after studies, the CEC of RA patients (SMD: 0.20, 95% CI: 0.02 to 0.37) increased, but the plasma HDL-C levels (MD: 3.63, 95% CI: - 0.13 to 7.39) remained at a comparable quantity after anti-rheumatic treatment comparing with the baseline. In addition, the funnel plot of included studies displayed a lightly asymmetry, while Egger's and Begg's test did not suggest the existence of publication bias. The quality of evidence was rated according to GRADE as moderate to very low.ConclusionThe current meta-analysis demonstrated that HDL-mediated CEC can be improved by the early control of inflammation and anti-rheumatic treatment in RA patients, which is independent of the plasma HDL-C levels. However, the results should be interpreted with caution because of low-quality and limited quantity of evidence. Future randomized controlled trials are needed to determine whether therapeutic strategies to enhance CEC in RA patients have beneficial effects for preventing CVD.

Dataset Information

Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein-Enriched Serum in Rheumatoid Arthritis.

Publications

Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein-Enriched Serum in Rheumatoid Arthritis.

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