VIENNA, Austria-Interleukin-6 (IL-6), rheumatoid factor, and chronic kidney disease predict endothelial dysfunction among rheumatoid arthritis (RA) patients and need to be suppressed to stave off atherosclerosis, according to new research presented here on Thursday at the Annual European Congress of Rheumatology of the European League Against Rheumatism (EULAR).

Moreover, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1) are biomarkers of the increased risk, the study showed.

"The major message is that you need to suppress inflammation and disease activity and that it's not inflammatory molecules like C-reactive protein, but a direct effect of cytokines from the joint released into circulation that cause the endothelial dysfunction that precedes cardiovascular disease in these patients," Patrick Dessein, MD, rheumatologist at Johannesburg Hospital in South Africa, tells CIAOMed. Specifically, he says, "disease modifying agents that most effectively suppress both cytokine and rheumatoid factor production may also be most effective at protecting against CV disease in RA, [and] interventions aimed at preserving renal function may need to be considered in CV disease prevention in RA."

 

New findings establish initial link to cardiovascular disease (CVD) in RA patients

The new research comprised three parts. First, Dessein et al compared biomarkers of endothelial dysfunction in 74 RA patients and 80 healthy control subjects before and after controlling for traditional CV risk factors including age; gender; race; smoking, alcohol, and exercise status; diabetes; waist circumference; systolic blood pressure; total cholesterol, high density lipoprotein (HDL) cholesterol, and triglycerides; and such nontraditional CV risk factors as high sensitivity C-reactive protein (hs-CRP), interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α). The second stage looked at the role of patient characteristics in endothelial dysfunction in the 74 RA patients. Third, researchers assessed the association between biomarkers of endothelial dysfunction and ultrasonographically determined common carotid artery intima-media thickness (CCA-IMT) and plaque in RA.

 

Circulating adhesion molecules predict risk

In general, the three biomarkers of endothelial dysfunction were higher in patients than in controls. "The initial essential link to CVD, endothelial dysfunction, can be assessed by these adhesion molecules," he says.

After controlling for all traditional CV risk factors, IL-6 predicted all three biomarkers, and rheumatoid factor titers and low glomerular filtration rate both predicted VCAM-1 and ICAM-1. The rheumatoid factor findings suggest that humoral immunity, rather than cellular immunity, is at play. Specifically VCAM-1 was associated with CCA-IMT and plaque in RA.

The nontraditional CV risk factors hs-CRP, IL-1, IL-6, and TNF-α were also each higher in patients than in controls. With regard to traditional CV risk factors, RA patients were older, exercised less, had a higher waist circumference, and had higher systolic blood pressure and triglyceride levels than RA-free controls. In addition, five RA patients had diabetes.

Reference:

Dessein P, Joffe BI, Singh S. Biomarkers of endothelial dysfunction, cardiovascular risk factors and atherosclerosis in rheumatoid arthritis. Presented at: The Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract THU0233.