Rheumatoid Arthritis Increases Risk of Cardiovascular Disease Events After Fragility Fracture

Patients who met the diagnostic criteria for rheumatoid arthritis (RA) had an increased risk of cardiovascular events following fragility fractures, according to data from the Rochester Epidemiology Project (REP). REP is a long-standing research database that collects demographic characteristics, medical diagnostic codes, surgical procedure codes, and death information for almost all of the residents of Olmsted County, Minnesota, via a comprehensive medical records linkage system. Results were published ahead of print in The Journal of Rheumatology on January 15, 2017.

An increased risk for both fractures and cardiovascular disease (CVD) has been well documented in patients with RA, but prior to this study the risk in patients with RA of developing CVD subsequent to fragility fractures had not been established.

In the study, investigators identified 1171 patients (822 women, 349 men) who met American College of Rheumatology (ACR) 1987 revised criteria for the classification of RA between January 1, 1955, and December 31, 1994, and matched them with patients without RA of the same sex and birth year. 

Patients in the non-RA cohort were assigned an index date corresponding to the date of RA incidence. Records were searched for the occurrence of fractures postdiagnosis or post-index date and for cardiovascular outcomes, defined as the earliest occurrence of ischemic heart disease (IHD) or heart failure (HF).

Fragility fractures were found in 406 patients in the RA cohort (301 women, 105 men) and 346 patients in the non-RA cohort (260 women, 86 men). Major osteoporotic fractures occurred in 318 patients in the RA cohort (234 women, 84 men) and 245 patients in the non-RA cohort (186 women, 59 men). CVD events occurred in 286 patients in the RA cohort and 225 patients in the non-RA cohort. Fragility fractures significantly increased the risk of subsequent CVD events in patients with RA (HR 1.81, 95% CI, 1.38-2.37), an effect not seen in the non-RA cohort (HR 1.18, 95% CI, 0.85-1.63). No significant differences were seen in women vs men. The increased risk of CVD in patients in the RA cohort following fragility fractures was independent of glucocorticoid use, hormone replacement therapy, and many established cardiovascular risk factors.

Summary & Clinical Applicability

“Fragility fractures in patients with RA are associated with an increased risk for the development of future CVD events (including both IHD and HF), independent of traditional CV risk factors,” wrote the investigators. 

“While shared risk factors likely account for this association, inflammation is a key pathogenic mechanism that is associated with both fragility fractures and CVD and could be an especially important explanation for our findings. Further studies are required to better address this hypothesis. Based on our results, patients with RA who have experienced a fragility fracture should be particularly screened for CVD and may warrant more aggressive preventive therapy.”

Study Limitations

• The study cohort (residents of Olmsted County, Minnesota) is predominantly white; therefore, results may not be generalizable to other populations.
• Most patients in the RA cohort were treated prior to the advent of biologic therapies, agents which may lower the risk of both fractures and CVD.
• The investigators were unable to determine the role of inflammatory cytokines due to a lack of data.
• Available records did not allow for an analysis of RA disease activity in all subjects over follow-up

Reference

Ni Mhuircheartaigh O, Crowson CS, Gabriel SE, et al. Fragility fractures are associated with an increased risk for cardiovascular events in women and men with rheumatoid arthritis: a population-based study [published online January 15, 2017]. J Rheumatol. doi:10.3899/jrheum.160651