June 12, 2007 — Men who carry the auto-antibody rheumatoid factor have an increased risk of heart disease than those who do not have the auto-antibody, a new study suggests.
The study, published online ahead of print in Heart, did not show any association between rheumatoid factor and risk of heart disease in women. The authors, led by Dr Christopher Edwards (University of Southampton, UK) say the findings in men add more weight to the growing evidence that inflammation is implicated in atherosclerosis. It also raises the possibility that auto-immune processes and rheumatoid factor in particular may actually have a role in the disease process itself.
Edwards et al explain that rheumatoid factor is an auto-antibody strongly associated with rheumatoid arthritis, but may be present in subjects many years before they develop the disease. The factor is also associated with other autoimmune rheumatic diseases, viral or bacterial infections and is present in as many as 15% of normal adults. Noting that chronic inflammatory diseases, such as rheumatoid arthritis, have been shown to increase the risk of ischemic heart disease, they hypothesized that rheumatoid factor may also identify subjects in the general population who have an increased likelihood of developing heart disease.
They investigated this idea in a population of elderly men and women who had taken part in the Hertfordshire Cohort Study. The study involved 567 men and 589 women born in Hertfordshire between 1931 and 1937 who were assessed for a history of ischemic heart disease, rheumatoid factor and traditional risk factors for heart disease. They were also assessed for other common auto-antibodies (antinuclear antibodies and anticardiolipin antibodies) to see if any effect observed was specific to rheumatoid factor or due to non-specific polyclonal B-cell expansion.
Results showed that rheumatoid factor was associated with about a three times increase in the risk ischemic heart disease in men, which could not be explained by traditional risk factors for heart disease.
There was no significant association between rheumatoid factor and heart disease in women or between the other auto-antibodies measured and heart disease in men or women.
Edwards et al say the association between rheumatoid factor and ischemic heart disease shown in this study is of a similar magnitude to that for diabetes and hypertension.
They note that although rheumatoid factor is strongly associated with rheumatoid arthritis, and that rheumatoid arthritis is associated with increased cardiovascular morbidity and mortality, the increased risk in this study is unlikely to be due to active rheumatoid arthritis or its treatment, as the prevalence of rheumatoid arthritis in men in the United Kingdom is only around 0.4%. In addition, after removing the 10 women and four men found to have rheumatoid arthritis from the analysis, the results did not change.
The authors suggest that the link between rheumatoid factor and heart disease provides further evidence of the importance of inflammation in heart disease and raises the possibility that autoimmune mechanisms may play a part. They say that this study cannot determine whether rheumatoid factor is a nonspecific marker of inflammation or is involved directly in the pathogenesis of atherosclerosis. But they add that the factor appears to cause direct tissue damage in rheumatoid arthritis as a constituent of immune complexes, perhaps by activating complement, and that it might cause damage to the endothelium in a similar way.
In addition, the lack of a relationship between the other auto-antibodies measured and heart disease suggests a unique role for rheumatoid factor in the pathogenesis of ischemic heart disease/atherosclerosis, they conclude.
Heart. Published online June 5, 2007.
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