AMSTERDAM, The Netherlands—High levels of cholesterol and other blood lipids in patients who will develop rheumatoid arthritis (RA) may predate RA onset by as much as 10 years, according to new research in the Annals of Rheumatic Diseases1 that sought to determine when dyslipidemia begins in early RA.

"Our study supports the observation that patients with rheumatoid arthritis have a more atherogenic lipid profile even in the preclinical phase of rheumatoid arthritis." —V.P. van Halm, MD, VU University Medical Centre in Amsterdam.
"This phenomenon starts more than 10 years before the clinical onset of rheumatoid arthritis," conclude the researchers led by V.P. van Halm, MD, of the VU University Medical Centre in Amsterdam. "Our study supports the observation that patients with rheumatoid arthritis have a more atherogenic lipid profile even in the preclinical phase of rheumatoid arthritis, which ultimately could explain the increased cardiovascular risk in patients with rheumatoid arthritis."

Researchers measured levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein AI (apo AI), apolipoprotein B (apo B), and lipoprotein(a) (Lp[a]) in 1078 stored, deep-frozen, serial blood bank samples of 79 blood donors who later developed RA. The samples were collected between 1984 and 1999. The researchers compared these samples with 1071 control samples matched for age, sex, and storage-time controls.

On average, the patients who went on to develop RA had 4% higher total cholesterol, 9% lower HDL, 17% higher triglyceride, and 6% higher apo B levels than matched controls (P <e;.05), the study showed.

Inflammation only partly to blame

The magnitude of the differences in lipid levels between groups with regard to C-reactive protein (CRP) was limited. For example, only 3.6% of the difference in HDL levels between the groups was with regard to the CRP concentrations. Secretory phospholipase A2 (sPLA2)  also only accounted for marginal differences on the atherogenic profiles between RA patients and controls.

"We show that inflammation is associated with (further) deterioration of the lipid profile, but inflammation can explain only a small part of the observed differences in lipids between people who develop RA and controls," the study authors write.

"Whether lipids modulate the susceptibility of inflammatory disease such as rheumatoid arthritis remains to be elucidated," they conclude. Several hypothesis exist. Perhaps, they write, a marginally deteriorated lipid level predisposes a person to inflammation or inflammatory disorders. "In other words, one or more of the examined lipids could have a regulatory effect on inflammation," or "a less favorable lipid profile is related to the development of rheumatoid arthritis by a common or linked background."

CIAOMed recently reported on data in The Journal of Rheumatology2 that suggested RA should be considered an independent cardiovascular risk factor and should trigger interventions to lower the low density lipoprotein (LDL) cholesterol in many RA patients who are not currently receiving such treatment.

 "Despite an inordinately high risk of cardiovascular events in RA, assessment of cardiovascular risks was uncommon in our practice, and cholesterol-lowering treatment was insufficiently prescribed," the authors of that study wrote.

References

1. van Halm VP, Nielen MMJ, Nurmohamed MT, et al. Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis. Ann Rheum Dis. 2007;66:184-188.
2. Soubrier M, Zerkak D, Dougados M. Indications for lowering LDL cholesterol in rheumatoid arthritis: an unrecognized problem. J Rheumatol. 2006;33:1766-1769.