There may also be an ACPA/BMI interaction at work in some cases. A recent study found a 20-fold increased RA risk for those with two or more ACPA antibodies on research assays and overweight/obese women compared with women with fewer than two ACPA antibodies and normal BMI in the Nurse’s Health Studies.8
“To me this indicates that perhaps men and women have different paths to RA in this framework,” he says. “ACPA status can define a phenotype that is more homogenous so it may be that the ACPA-negative aspect makes this a more malleable phenotype. Perhaps the obesity is driving RA risk for this subset instead of just being a bystander.”
Qin and colleagues completed a meta-analysis of 11 studies on the subject. Their results showed that the higher the BMI, the higher the relative risk of RA. Overall, there was a 31% increase in RA for those with obesity when compared to normal body mass index.9
“Something to consider when looking at these results is that these studies typically compare one BMI category to another,” Dr. Sparks says. “This implies that if someone lost weight and changed from the obese to normal category, their risk for RA would be reduced. However, few studies have actually evaluated whether weight change also affects RA risk.”
Food & Drink Intake
Food and drink intake are also linked to RA risk, according to the results of multiple studies. Increased sugar-sweetened soda intake was associated with RA, especially the older-onset, seropositive phenotype.10 On the other side, consuming one to three servings of fish per week showed a protective effect (relative risk ratio of 0.76) compared with less frequent intake.11 Moderate alcohol intake also had a modest protective effect compared with infrequent drinking.12
Dr. Sparks and colleagues assessed the effect of healthful eating on RA risk using the Healthy Eating Index scale. Those who ate the healthiest had a significantly decreased risk for rheumatoid arthritis. The result was especially strong among those diagnosed with RA before 55 years of age.13
Studies of the Etiology of Rheumatoid Arthritis (SERA) findings from first-degree relatives of RA patients who were showing no signs of the disease did see an association of smoking and joint inflammation, but no association with BMI.14 This gives less clarity on the issue of when the obesity/RA hazard period begins.
Consistent Picture
“There is a very consistent picture developing whether you look at the animal studies, the molecular studies or the human studies for RA risk,” says Dr. Sparks. “We see the same cytokines and inflammatory cells in obesity studies that are also important in RA pathogenesis. In the epidemiologic results in the preclinical period, we are finding the observations we would expect from those molecular underpinnings.”
