HERAKLION, Greece—Metabolic syndrome is not more common in middle and older age rheumatoid arthritis (RA) patients than in non-RA controls, but it tends to correlate with RA disease activity, which adds to the evidence that inflammation plays a role in the high cardiovascular risk associated with RA, according to a new study in Annals of Rheumatic Diseases.¹ Related work in a similar study suggests that a reduced level of inflammatory markers associated with metabolic syndrome might be an additional benefit of TNF inhibitor therapy.²

"RA patients have an increased risk and a higher mortality from cardiovascular diseases; thus rheumatologists should be aware of those metabolic syndrome risk factors and attempt to modify them accordingly in order to prevent cardiovascular disease," researcher Dimitrios T. Boumpas, MD, rheumatologist at the University of Crete in Heraklion, Greece, told CIAOMed.

Metabolic syndrome (also known as Syndrome X) refers to a constellation of symptoms including abdominal obesity, hypertension, high triglycerides, elevated glucose, and low high-density lipoprotein (HDL) cholesterol. Until recently, the very existence of this syndrome as a diagnostic entity was controversial, with the American Heart Association and the National Heart, Lung, and Blood Institute referring to it as a real and growing health problem and the American Diabetes Association publicly discounting its significance. The warring groups have called a truce stating that they are all committed to reducing the burden of cardiovascular disease.

In the retrospective, cross-sectional study, Dr. Boumpas and colleagues compared 200 RA out-patients with 400 age- and sex-matched healthy controls. The presence of metabolic syndrome was assessed according to the Adult Treatment Panel (ATP) III criteria. RA disease activity was assessed by the disease activity score of 28 joints (DAS28). Researchers conducted a standard clinical evaluation and patients answered a health and lifestyle questionnaire.

The overall prevalence of metabolic syndrome was similar in both groups: 44% in RA patients and 41% in controls, the study showed. Patients with RA were more likely to have low HDL cholesterol compared to controls, and controls were more likely to have increased waist circumference and/or elevated blood pressure.

Elevated levels of inflammatory markers such as C-reactive protein (CRP) associated with metabolic syndrome are thought to be the result of production of such mediators by omental fat, which is typically more extensive in subjects with the abdominal obesity that is one hallmark of the syndrome.

Presence of Risk Factors Correlate With High DAS28

Among RA patients, the risk of having moderate-to-high disease activity or a DAS28 >3.2 was significantly higher in patients with symptoms of the metabolic syndrome compared to those without metabolic syndrome.

"Our results suggest that, although the prevalence of MetS in RA patients is not different than [that] in a relative risk population, the prevalence of MetS correlates with disease activity," the authors write.

"Our data that correlate DAS28, a combined inflammatory index of RA, with metabolic syndrome further support the role of chronic inflammation in insulin resistance/metabolic syndrome development," according to the researchers. "On the other hand, the presence of chronic inflammation could explain, in part, the high prevalence of metabolic syndrome among RA patients," Dr. Boumpas told CIAOMed.

Role of TNF

The new study has several limitations. For one, 40% of the RA patients were taking anti-TNF blockers, and as a result, the prevalence of metabolic syndrome could have been underestimated. Studies have shown a positive effect of anti-TNF treatment on insulin resistance.

Bernstein et al reported that etanercept (EnbrelR) can improve several inflammatory markers in patients with metabolic syndrome.2  Patients who took etanercept had lower levels of C-reactive protein and higher levels of adiponectin, according to the study in the April 25 issue of Archives of Internal Medicine.

Dr. Boumpas said that data on inflammatory markers were not collected in the study of metabolic syndrome in RA patients but are an area of interest. "We will now prospectively investigate the effect of newer potent therapies—namely the anti-TNF—in the metabolic syndrome development," Dr. Boumpas told CIAOMed. "Our study hypothesis is that TNF is a major contributor to the metabolic syndrome."

References