In this study of middle‐to‐old aged people, MetS was found to be common both in patients with rheumatoid arthritis (44%) as well as in age‐matched and sex‐matched controls (41%), and to correlate with disease activity. The prevalence of MetS was comparable between patients and controls both in the whole study population and in the different age groups. This is higher than what has recently been reported for the Greek adult population in the region of Attica (ATTICA study, prevalence 19.8%). Such a discrepancy may be attributed to differences in the selection criteria of the study population: participants in the ATTICA study were free of CHD, stroke, diabetes mellitus or any atherosclerotic disease, with a significantly lower mean age than our study population.23
The prevalence of MetS in our population was also assessed according to the criteria recently proposed by the American Heart Association/National Heart, Lung, and Blood Institute.24
As expected, prevalence was higher compared with the NCEP ATPIII criteria, yet no significant difference was found between patients and controls (data not shown).
When rheumatoid arthritis disease‐related factors were examined for a possible correlation with the presence of MetS, no significant differences were found regarding disease duration. Accordingly, in previous studies there was no relationship between disease duration and risk of CHD in patients with rheumatoid arthritis.21,25
It has been proposed that the increased risk of CHD may precede the clinical onset of rheumatoid arthritis,21
and that there is a preclinical phase of rheumatoid arthritis during which inflammatory activity and serological disturbances occur.22
Other disease‐related factors, such as extra‐articular manifestations and rheumatoid factor seropositivity, did not correlate with the presence of MetS.
In this study, a significant correlation between DAS28 and individual components of MetS—namely, systolic blood pressure (p
0.01) and a trend towards an inverse correlation with HDL‐C (p
0.056)—was found. Significantly more patients without MetS a had low DAS28 index (
3.2) compared with patients with MetS (16.5% v
0.003). A significant linear correlation (β
0.001) was found between the DAS28 and the number of MetS components present (fig 1). Moreover, in a multivariate model assessment, the risk of having moderate‐to‐high DAS28 was found to be significantly higher for patients with MetS compared with those without MetS components (p
0.016) even after adjusting for rheumatoid arthritis treatments, demographics and behavioural factors (table 5). On the contrary, the use of biologicals, steroids or MTX was not associated with a higher risk of DAS28. Taken together, these data suggest that rheumatoid arthritis disease activity correlates with MetS, implicating a significant role for the inflammatory burden in the evolution of metabolic disturbances in patients with rheumatoid arthritis.
Metabolic syndrome is considered a proinflammatory state, whereby the expanded adipose tissue is thought to represent a source of proinflammatory cytokines (ie, interleukin 6 and tumour necrosis factor (TNF)α).26
There is increasing evidence that insulin resistance, the basic metabolic disturbance of MetS, is not only associated with the abundance of proinflammatory cytokines but also is the direct result of this burden.27,28
TNFα interferes with insulin signalling, both inducing down regulation of the insulin‐responsive glucose transporter expression in adipocytes and muscle,29
and reducing the tyrosine kinase activity of the insulin receptor.30
Our data, which correlate DAS28, a combined inflammatory index of rheumatoid arthritis, with MetS, further support the role of chronic inflammation in insulin resistance/MetS development.
The results of this study must be interpreted within the limitations of the methods, the major limitation being the small number of patients studied, especially men. Also, we did not have information on inflammatory markers such as hs‐CRP in both groups, and hence we were unable to directly examine the possible relationship of these factors with the presence of MetS. We cannot exclude the possibility of patient selection bias, as our centre is a tertiary referral centre. At the time of assessment, the vast majority of the patients (97.5%) were on treatment for rheumatoid arthritis and about 40% of them were taking anti‐TNF agents. Published reports support a favourable effect of anti‐TNF treatment on insulin resistance in patients with rheumatoid arthritis or ankylosing spondylitis, and an increase in HDL cholesterol.31,32
We can say that as almost 40% of our patients were on anti‐TNF treatment, we may have underestimated the prevalence of MetS. We are currently prospectively investigating the effect of anti‐TNF treatment on MetS.
In summary, the prevalence of MetS appears to be high—albeit comparable—in patients with rheumatoid arthritis and in controls. Rheumatoid arthritis disease activity correlates with the presence of MetS, implicating a role for inflammation in MetS. Larger studies are required to clarify the importance of MetS in this population.