Women who are overweight or obese, particularly those becoming so by late adolescence, have an elevated risk for developing rheumatoid arthritis.

by Nancy Walsh, Senior Staff Writer, MedPage Today
August 01, 2014

Women who are overweight or obese, particularly those who acquire the excess weight by late adolescence, have an elevated risk for developing rheumatoid arthritis (RA), analysis of data from two prospective studies showed.

While there was a nonsignificant trend for increased risk for RA among all overweight or obese women (P=0.068), there was a 35% higher risk among those with body mass index (BMI) values of 25 or higher at age 18 (HR 1.35, 95% CI 1.11-1.64, P=0.002), according to Bing Lu, MD, DPH, and colleagues from Harvard University’s medical and public health schools in Boston.

In addition, the risk among those women for developing seropositive RA — generally considered more severe — increased by almost 50% (HR 1.49, 95% CI 1.08-2.06, P<0.001), the researchers reported online in Annals of the Rheumatic Diseases.

Obesity contributes to the development of multiple disease states, including osteoarthritis and diabetes.

“One pathway by which obesity may increase the risk of several diseases is via systemic inflammation. Adipose tissue secretes proinflammatory adipocyte-derived cytokines, or adipokines, into the circulation,” explained Lu and colleagues.

However, previous studies examining the relationship between obesity and RA have had conflicting results, and the researchers suggested that risk factors may differ according to age at disease onset.

To examine this hypothesis, they analyzed data from the Nurses’ Health Study (NHS) and the Nurses’ Health Study II (NHSII), comparing risks for women who developed RA at or before age 55 with those whose disease onset was later.

The analysis included 109,896 women in NHS, which began enrolling participants in 1976, and 108,727 from NHSII, which started in 1989.

Every 2 years, women in both cohorts filled out questionnaires on health, lifestyle, and disease diagnoses.

Those whose BMI was 25 to 30 were considered overweight, and obesity was defined as BMI above 30.

During 32 years of follow-up in NHS, 826 cases of RA were reported and verified, along with 355 cases during 20 years of follow-up in NHSII.

In the earlier cohort, age at diagnosis was a decade older than in the later group (58 versus 48 years), and 41% of cases were diagnosed before age 55, compared with 83% of cases in NHSII.

mong those diagnosed before 55 in the combined groups, the hazard ratios for RA were 1.45 (95% CI 1.03-2.03) for women who were overweight and 1.65 (95% CI 1.34-2.05) for those who were obese.

The population-attributable risk for the two categories of excess weight was 10% in NHS and 40% in NHSII.

The researchers also calculated the risk according to cumulative average BMI and found a hazard ratio of 1.23 (95% CI 1.06-1.44) for BMI in the overweight range and 1.34 (95% CI 1.06-1.68, P<0.001) for values considered obesity.

They also found a “dose effect,” in that 10 cumulative years of obesity resulted in a 37% higher risk of onset earlier than 55 (HR 1.37, 95% CI 1.11-1.69).

“Our study findings are consistent with those of prior studies that identified an association between obesity and RA diagnosis among younger women,” they noted.

For instance, in a Minnesota case-control study, a significant association was seen between obesity and the development of RA before age 60 (OR 1.32, 95% CI 1-1.72) but not after that age (OR 1.15, 95% CI 0.82-1.61).

“Given the recent rapid increase in the prevalence of obesity, this risk factor appears to have a significant impact on the incidence of RA and may account for a large proportion of the recent increase in incidence of RA among women,” the authors of the case-control study wrote.

Adipocytes can produce inflammatory markers such as tumor necrosis factor, interleukin-6, and C-reactive protein, which have been detected in individuals with preclinical disease, according to Lu and colleagues.

“Hence, there is biological plausibility to implicate obesity in RA pathogenesis,” they observed.

The very high risk seen among women who were obese at age 18 underscores “the public health importance of combatting the obesity epidemic at all ages,” they wrote.

Limitations of the study included reliance on BMI as a measure for bodily fat, which may be less accurate in older individuals who lose lean body mass, and the possibility that a poor diet associated with obesity also may contribute to RA risk.

• Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania