Background/Purpose: Rheumatoid Arthritis (RA) is associated with an increased risk for both fracture (fx) and cardiovascular disease (CVD) and there is increasing evidence establishing a link between these conditions. In addition to common shared risk factors (e.g., smoking), chronic inflammation may also be key to the pathogenesis of bone loss and CVD. Our aim was to determine whether an incident fx following RA diagnosis increases the risk for subsequent CVD.

Methods: We studied a population-based inception cohort (age ≥18 yrs) who fulfilled 1987 ACR criteria for RA between 1955 and 2007 and an equal number of age- and sex-matched non-RA subjects from the same underlying population. All incident fxs, CVD events (including ischemic heart disease [IHD] and heart failure [HF]) and CVD risk factors (smoking, diabetes mellitus, hypertension, dyslipidemia) were identified through a review of complete (inpatient and outpatient) community medical records. Pathologic fxs and fxs resulting from severe trauma (e.g., motor vehicle accidents) were excluded from analyses. Subjects with prior CVD were also excluded. Adjusting for age, sex, calendar year and CVD risk factors, Cox proportional hazard models were used to examine the risk for CVD following incident fx (modeled as a time-dependent covariate) in both RA and non-RA subjects. CVD risk factors were also modeled as time-dependent covariates.

Results:   We identified 1171 RA and 1171 non-RA subjects (for each group: mean age ± SD, 57 ± 16 yrs; 822 [70%] women), of whom 137 RA and 139 non-RA subjects with prior CVD were excluded. Over a follow-up of 14,125 person-years (py) (median, 10 years) and 16,125 py (median, 12 years) for RA and non-RA subjects, respectively, 406 RA and 346 non-RA subjects had an incident fx and 284 RA and 225 non-RA subjects developed CVD. Among RA subjects, but not non-RA subjects, there was an increased risk for CVD following an incident fx (Table). Results were similar following a fx at a major osteoporotic fx site (hip, spine, wrist, shoulder) [results not shown].

Conclusion:  In women and men with RA, an incident fracture is associated with an increased risk of subsequent CVD. Although the mechanism underlying this association remains to be clarified, a new fx in an RA patient should be considered a sentinel event that prompts further evaluation of their cardiovascular risk.