Effect Modification of Cigarette Smoking on the Relationship between Post-traumatic Stress Disorder, Other Mental Health Conditions and Rheumatoid Arthritis Risk: A Large Case-Control Study in U.S. Veterans.

Objective

We examined associations of post-traumatic stress disorder (PTSD) and other mental health disorders (OMH) with rheumatoid arthritis (RA), accounting for effects of smoking.

Methods

We conducted a matched case-control study, identifying incident RA cases and controls using national Veteran Health Administration data (2006-2019). PTSD/OMH exposures prior to RA diagnosis were identified using administrative/diagnostic codes. Conditional logistic regression examined associations of RA (vs. no-RA) with PTSD (±OMH) and OMH. Relative Excess Risk of Interaction was calculated between OMH/PTSD and smoking using standard multivariable logistic regression with standard errors clustered within match groups stratified by ever/never smoking. Analyses were repeated excluding individuals without a visit in the previous year.

Results

A total of 357,361 Veterans (mean age 53 years, 87% male, 70% ever smoked) were studied. Both PTSD (19% vs. 13%) and OMH (31% vs. 26%) were more frequent in RA than controls. Multivariable analyses demonstrated associations of PTSD and OMH with RA with evidence of PTSD/OMH-smoking interactions; associations were stronger in never (aORs 1.54/1.40, respectively) vs. ever smokers (aORs 1.20/1.08). Excluding individuals without a healthcare visit, PTSD and OMH remained associated with seronegative RA in ever (aOR 1.17; 95% CI 1.09-1.26 and aOR 1.14; 95% CI 1.06-1.21) and never smokers (aOR 1.37; 95% CI 1.16-1.62 and aOR 1.27; 95% CI 1.10-1.47); similar associations of PTSD/OMH with seropositive RA were not observed.

Conclusion

This study demonstrates that the relationships of PTSD (and OMH) with RA differ by smoking status. The strongest associations between PTSD/OMH and incident RA were among never smokers and in seronegative disease.