Roles of Postdiagnosis Accumulation of Morbidities and Lifestyle Changes in Excess Total and Cause-Specific Mortality Risk in Rheumatoid Arthritis

Abstract

Objective: To elucidate how postdiagnosis multimorbidity and lifestyle changes contribute to the excess mortality of rheumatoid arthritis (RA).

Methods: We performed a matched cohort study among women in the Nurses' Health Study (1976-2018). We identified women with incident RA and matched each by age and year to 10 non-RA comparators at the RA diagnosis index date. Specific causes of death were ascertained via death certificates and medical record review. Lifestyle and morbidity factors were reported biennially; 61 chronic conditions were combined into the Multimorbidity Weighted Index (MWI). After adjusting for baseline confounders, we used inverse probability weighting analysis to examine the mediating influence of postindex MWI scores and lifestyle factors on total, cardiovascular, and respiratory mortality, comparing women with RA to their matched comparators.

Results: We identified 1,007 patients with incident RA and matched them to 10,070 non-RA comparators. After adjusting for preindex confounders, we found that hazard ratios (HRs) and 95% confidence intervals (95% CIs) were higher for total mortality (HR 1.46 [95% CI 1.32, 1.62]), as well as cardiovascular (HR 1.54 [95% CI 1.22, 1.94]) and respiratory (HR 2.75 [95% CI 2.05, 3.71]) mortality in patients with RA compared to non-RA comparators. Adjusting for postindex lifestyle factors (physical activity, body mass index, diet, smoking) attenuated but did not substantially account for this excess RA mortality. After additional adjustment for postindex MWI scores, patients with RA had HRs of 1.18 (95% CI 1.05, 1.32) for total, 1.19 (95% CI 0.94, 1.51) for cardiovascular, and 1.93 (95% CI 1.42, 2.62) for respiratory mortality.

Conclusion: We found that MWI scores substantially accounted for the excess total and cardiovascular mortality among women with RA. This finding underscores the importance of monitoring for the total disease burden as a whole in monitoring patients with RA.

Figure 1.

Cohort construction diagram. For each incident rheumatoid arthritis (RA) case, 10 non-RA comparators were matched on age and calendar time. The follow-up for this current study started at the time of RA diagnosis or the comparable date for the comparators (index date). Abbreviations: f/u: follow-up; IPW: inverse probability weights.

Figure 2.

Accumulation of multimorbidity after the index date of RA diagnosis (n=1,007) or matched date for comparators (n=10,070) for women in the Nurses’ Health Study, as quantified by the Multimorbidity Weighted Index. The mean slope difference represents the additional accumulation of the Multimorbidity Weighted Index per 10 years [95% confidence interval] among women with RA compared to their matched non-RA comparators, as well as the p for interaction. RA: rheumatoid arthritis.

Figure 3.

Accumulation of the major components (musculoskeletal, cardiovascular, pulmonary, endocrine, gastrointestinal, and nervous) of the Multimorbidity Weighted Index after the index date of RA diagnosis (n=1,007) or matched date for comparators (n=10,070) for women in the Nurses’ Health Study. The in-figure numbers are the mean slope differences that represent additional increase of each component Multimorbidity Weighted Index per 10 years [95% confidence interval] among women with RA compared their matched non-RA comparators, as well as the p for interaction. See Supplemental Table for further information on the components. RA: rheumatoid arthritis.

Figure 4.

Changes in continuous measures of lifestyle factors (body mass index, moderate to vigorous physical activity, dietary intake, and smoking) over time after the index date of RA diagnosis (n=1,007) or matched date for comparators (n=10,070) for women in the Nurses’ Health Study. The numbers represent the mean slope difference per 10 years [95% confidence interval] comparing women with RA to their matched non-RA comparators, as well as the p for interaction. AHEI: Alternate Healthy Eating Index; BMI: body mass index; RA: rheumatoid arthritis.