The presence of comorbidities, including inflammatory bowel disease, type 1 diabetes, venous thromboembolism, cardiovascular disease, and obstructive sleep apnea, may either predispose patients to rheumatoid arthritis (RA) development or may manifest following an RA diagnosis. Investigators of the research presented in Mayo Clinic Proceedings suggest the importance of screening for RA in these patient populations.
Researchers conducted a case-control study to explore comorbidities in RA. This included assessing the prevalence of comorbidities present in RA; targeting which comorbidities may predispose a person to develop RA; and identifying which comorbidities are most likely to develop following an RA diagnosis. Data were collected via a questionnaire from the Mayo Clinic Biobank. RA cases were matched 1:3 to control cases based on age, sex, recruitment year and location, and distance from recruitment location.
The cohort included 821 RA cases and 2455 controls (N=3276). At the index date, the mean age was 50±16 years. Patients in the RA group had a higher raw number of comorbidities compared with controls (median 5 vs 4; interquartile range [IQR] 3-8 vs 2-6, P <.001) but did not have more comorbidities at RA diagnosis index date (median 1 vs 1; IQR 0-3 vs 0-2, P =.49).
Investigators first calculated the prevalence of each of 74 comorbidities in both cases and controls at the time of the baseline questionnaire. After adjustments, many comorbidities were found to be associated with RA: cataracts, epilepsy, fibromyalgia, gastroesophageal reflux disease, inflammatory bowel disease, myocardial infarction, obstructive sleep apnea, osteoarthritis, pulmonary fibrosis, venous thromboembolism, and other rheumatic autoimmune disorders. Relative to RA diagnosis, the timing of comorbidity development “varied significantly.”
Inflammatory bowel disease, osteoarthritis, type 1 diabetes, and venous thromboembolism were identified as the 4 comorbidities that commonly preceded RA diagnosis. Other conditions, including hypo- and hyperthyroidism, stroke, and other rheumatic autoimmune disorders, more commonly occurred prior to RA diagnosis in RA cases, relative to controls.
Among RA cases relative to controls, myocardial infarction and venous thromboembolism occurred with increased frequency; congestive heart failure and obstructive sleep apnea also trended toward significance, per researchers, with an increased occurrence in RA cases relative to controls following the index date.
Sensitivity analyses were conducted in a subset of RA cases with incident RA. In this group, several comorbidities, including fibromyalgia, inflammatory bowel disease, osteoarthritis, pulmonary fibrosis, a rheumatologic autoimmune disorder, and venous thromboembolism, were significant at any time, whereas inflammatory bowel disease and osteoarthritis were significant prior to RA.
The incident cohort also demonstrated statistically significant associations not present in the full cohort, including hyper- and hypothyroidism at any time and before RA diagnosis, and other rheumatologic autoimmune disorders before RA diagnosis.
Study limitations include the use of a convenience sample and its associated potential for selection bias, as well as limited generalizability. RA diagnosis timing and comorbidity data relied on patient self-report and may have led to misclassification bias. Finally, there is a potential for unmeasured residual confounding due to the observational nature of the study.
“We found an association between RA and pre-existing comorbidities … which provides opportunities for earlier detection of RA,” the researchers concluded. “In addition, the associations with cardiovascular disease, [venous thromboembolism], and [obstructive sleep apnea] after RA diagnosis emphasize the importance of screening for these comorbidities among RA patients.”
Future studies, they added, should investigate why the overlap between RA and these comorbidities occurs.
Kronzer VL, Crowson CS, Sparks JA, Myasoedova E, Davis JM III. Comorbidities as risk factors for rheumatoid arthritis and their accrual after diagnosis. Mayo Clin Proc. 2019;94(12):2488-2498.