Improvements in High-Density Lipoprotein Quantity and Quality Contribute to the Cardiovascular Benefits by Anti-tumor Necrosis Factor Therapies in Rheumatoid Arthritis: A Systemic Review and Meta-Analysis

Abstract

Objective: Inflammation plays important role in atherosclerotic cardiovascular diseases (CVDs), but the interaction between the inflammation and lipid profile is largely unrevealed in humans. Patients with rheumatoid arthritis (RA) suffer from a higher risk of CVDs. Decreased total cholesterol (TC) and high-density lipoprotein (HDL) were prevalent in patients with RA. Anti-tumor necrosis factor (TNF) therapies relieve disease activity and decrease CVDs risk in RA, but their comprehensive effects on the lipid profile are unclear. This study aims to investigate the changes in blood lipid profile along time in the patients with RA accepting anti-TNF therapies by meta-analysis.Methods: The MEDLINE, the Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for eligible literature. Data of lipids were classified into short-, mid-, and long-term according to treatment duration. Meta-analyses were performed to compare the lipid levels before and after treatments.Results: A total of 44 records and 3,935 patients were included in the meta-analyses. Anti-TNF therapies were associated with significant increase in TC [mean difference (MD): +0.14, +0.23, and +0.26 mmol/l, respectively] and HDL (MD): +0.11, +0.12, and +0.11 mmol/l, respectively) in the short-, mid-, and long-term; anti-TNF therapies were associated with increased low-density lipoprotein (LDL) (MD: +0.06 mmol/l) and apolipoprotein A1 (ApoA1) (MD: +0.07 g/l) in the short-term, but not in the mid-term and long-term; triglyceride (TG) and apolipoprotein B (ApoB) do not change significantly in all the periods; proatherosclerotic indexes (TC/HDL, ApoB/ApoA1, and LDL/HDL) tend to decrease in the short- and mid-term, but return to baseline in the long-term after TNF inhibition.Conclusion: Anti-TNF therapies were related to a long-term raised HDL level, which, together with evidence of improved HDL function, may contribute partially to the decreased CVDs risk by TNF inhibition.

Dysfunctional antioxidant capacity of high‐density lipoprotein in rheumatoid arthritis

“…On the contrary, DMARDs or biological therapies can also influence the functionality of lipoproteins, although there are few studies on this topic and with contradictory results. 52,53 Regarding biological therapies, Popa et al described a beneficial effect on HDL antioxidative capacity that significantly improved after anti-tumour necrosis factor therapy with infliximab. 54 Differing from these previous findings, the present study found no differences in relation to biological therapies and functional lipid metabolism in RA patients, or with the presence or not of plaque or with the cIMT value.…”

“…Interestingly, we observed in the current study that patients with plaque were taking a significantly lower equivalent dose of prednisone than those without plaque. On the contrary, DMARDs or biological therapies can also influence the functionality of lipoproteins, although there are few studies on this topic and with contradictory results 52,53 . Regarding biological therapies, Popa et al described a beneficial effect on HDL antioxidative capacity that significantly improved after anti‐tumour necrosis factor therapy with infliximab 54 .…”

Cystic fibrosis and fat malabsorption: Pathophysiology of the cystic fibrosis gastrointestinal tract and the impact of highly effective CFTR modulator therapy

“…In addition, a direct correlation between serum TNF‐α and plasma triglyceride levels in adolescents with CF has been described by Levy et al, 139 although the finding was not confirmed in another study 145 . In patients with Crohn's disease and rheumatoid arthritis, anti‐TNF therapies can be associated with increased total and HDL cholesterol 170,171 . A retinoic acid analog (fenretinide) and antioxidants (glutathione and deferoxamine) with anti‐inflammatory activities also have been shown to partially correct oxidative stress and lipid imbalance in CFTR‐deficient epithelial cells 172 …”

“…145 In patients with Crohn's disease and rheumatoid arthritis, anti-TNF therapies can be associated with increased total and HDL cholesterol. 170,171 A retinoic acid analog (fenretinide) and antioxidants (glutathione and deferoxamine) with anti-inflammatory activities also have been shown to partially correct oxidative stress and lipid imbalance in CFTR-deficient epithelial cells. 172 The prevalence of dyslipidemias is likely to increase in the era of highly effective CFTR modulators because life expectancy of pwCF is steadily increasing.…”