Elevated levels of small, low-density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis: possible contribution of phospholipase A2 to this atherogenic profile

Arthritis Rheum. 2001 Dec;44(12):2761-7. doi: 10.1002/1529-0131(200112)44:12<2761::aid-art463>3.0.co;2-5.


Objective: This work studied the presence of inflammatory and atherogenic lipoprotein markers that could explain the high incidence of cardiovascular disease (CVD) reported in rheumatoid arthritis (RA) patients.

Methods: Inflammatory markers were 1) soluble adhesion molecules (intercellular adhesion molecule [ICAM] and vascular cell adhesion molecule [VCAM]), 2) C-reactive protein (CRP), 3) fibrinogen (Fb), 4) cytokines (interferon-gamma [IFNgamma], tumor necrosis factor alpha [TNFalpha]), and 5) secretory group IIA phospholipase A2 (sPLA2-IIA). Atherogenic lipoprotein markers were 1) the size distribution of plasma lipoprotein subclasses, and 2) the binding affinity of low-density lipoprotein (LDL) to chondroitin 6-sulfate glycosaminoglycan (GAG).

Results: RA patients (n = 31) and matched controls (n = 28) had similar plasma concentrations of total cholesterol, triglycerides, Apo B, Apo A-I, very low-density lipoprotein, intermediate-density lipoprotein, and high-density lipoprotein (HDL). RA patients had significantly higher plasma levels of sPLA2-IIA, ICAM, CRP, Fb, TNFalpha, and IFNgamma compared with controls. RA patients also had significantly higher levels of small, dense LDL-1 (P < 0.05) and lower levels of small HDL-2 particles (P < 0.001) compared with controls. In addition, LDL from RA patients had a significantly higher binding affinity (Kd) to GAG (mean +/- SD Kd 204+/-22.4 nM Apo B) than did LDL from control subjects (Kd 312+/-36 nM Apo B) (P < 0.05). This Kd value showed a significant negative correlation with the plasma levels of LDL-1 (r = -0.566, P < or = 0.004). In RA patients, a significant positive correlation was obtained between sPLA2-IIA and CRP, ICAM, and LDL-1. HDL-2 showed a negative correlation with sPLA2-IIA.

Conclusion: These atherogenic lipoprotein factors combined with the presence of chronic inflammation may contribute to the high CVD-related mortality in RA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arteriosclerosis / blood*
  • Arteriosclerosis / epidemiology
  • Arteriosclerosis / immunology
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / immunology
  • Biomarkers
  • C-Reactive Protein / metabolism
  • Female
  • Fibrinogen / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / blood
  • Interferon-gamma / blood
  • Lipoproteins, LDL / blood*
  • Male
  • Middle Aged
  • Phospholipases A / blood*
  • Phospholipases A2
  • Risk Factors
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / blood


  • Biomarkers
  • Lipoproteins, LDL
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma
  • Fibrinogen
  • C-Reactive Protein
  • Phospholipases A
  • Phospholipases A2