title: Serum levels of lipoprotein(a) and E-selectin are reduced in rheumatoid arthritis patients treated with methotrexate or methotrexate in combination with TNF-α-inhibitor.
abstract: OBJECTIVE
  To examine the effect of methotrexate (MTX) with or without tumor necrosis factor alpha (TNF-α)-inhibitors on serum lipoprotein(a) (s-Lp(a)), and to explore a possible relationship between s-Lp(a) and endothelial function (EF) in terms of serum levels of adhesion molecules and reactive hyperaemic index (RHI) in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Serum levels of Lp(a), endothelial adhesion molecules, RHI and inflammatory markers were studied in 64 RA patients, starting with either MTX (n=34) or MTX+TNF-α-inhibitor treatment (n=30) at baseline and after 6 weeks and 6 months.
  
  
  RESULTS
  Compared to baseline values, s-Lp(a) was significantly reduced after 6 weeks (p=0.001) and 6 months (p=0.001) in RA patients treated with MTX, and after 6 weeks (p=0.001) in the MTX+TNF-α-inhibitor group. A non-significant reduction was found after 6 months (p=0.102) in the MTX+TNFα-inhibitor group. Serum E-selectin (s-E-selectin) was significantly reduced in both RA treatment groups at both control points. S-Lp(a) correlated positively with s-E-selectin at baseline (p=0.004), and change in s-E-selectin correlated with the change in s-Lp(a) during follow-up (p6weeks= 0.008, p 6months=0.009). No association was found between s-Lp(a) and the other adhesion molecules and RHI.
  
  
  CONCLUSIONS
  MTX or MTX combined with a TNFα-inhibitor appears to significantly reduce Lp(a). This finding indicate that s-Lp(a) might be related to systemic inflammation, or that the examined drugs might reduce s-Lp(a) by other mechanisms. Anti-inflammatory treatment might be a novel therapeutic option to decrease s-Lp(a). The associations between s-E-selectin and s-Lp(a) suggest an interaction between these factors, or a common cause.
authors: Oslo University, Norway. gunn.hjeltnes@revmatismesykehuset.no
authors: Gunnbjørg
authors: G
authors: Hjeltnes
authors: Ivana
authors: I
authors: Hollan
authors: Oystein
authors: O
authors: Førre
authors: Allan
authors: A
authors: Wiik
authors: Torstein
authors: T
authors: Lyberg
authors: Knut
authors: K
authors: Mikkelsen
authors: Stefan
authors: S
authors: Agewall
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D019040:E-Selectin / Q000097:blood* / Q000502:physiology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects / Q000502:physiology; D017270:Lipoprotein(a) / Q000097:blood* / Q000502:physiology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D019040:E-Selectin; C573420:ICAM1 protein, human; D007074:Immunoglobulin G; D017270:Lipoprotein(a); D018124:Receptors, Tumor Necrosis Factor; C546936:SELE protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate