| Summary: | Most studies of mortality in rheumatoid arthritis patients (RA) have found increased mortality rates compared with the general population, and the majority suggest that one third to one half of the premature deaths in RA are due to increased cardiovascular disease (CVD), including myocardial infarction (MI) and cerebrovascular accidents (CVA). The increased risk of CVD mortality is not explained by traditional risk factors. The risk could be mediated by the deleterious effects of glucocorticoids (GC) used to treat RA. Alternatively, GC may have cardio-protective effects mediated by their anti-inflammatory and anti-proliferative actions in the endothelial wall, especially at low doses. Little is known regarding the long-term effects of GC on the development of CVD.
A systematic review and a meta-analysis of all observational studies was conducted and described in Chapter two. This study found that study design is the main driver in the reported variation in mortality. The increased mortality was attributable to increased death from MI and CVA.
In Chapters three and four, we assessed the risk of MI and CVA associated with the use of GC, respectively. We assembled a large population-based cohort using administrative health data that included cases with newly-diagnosed RA that were not exposed to GC prior to disease onset. Thus, for the first time, we assessed GC exposure over the entire course of the disease. We used comprehensive GC exposure measures that considered actual and past cumulative exposure individually or together. In addition to the traditional method that considers the lifetime past cumulative exposure measures (duration of use and dose) regardless of recency of use, we used a novel time-dependent method to evaluate if weighting for recency of use would improve the prediction of MI and CVA risk. This thesis has addressed the associated risk of CVD in patients with RA. Further, we have comprehensively assessed the association between GC use and risk of MI and CVA in unique cohort of patients with RA. Our results showed that GC use is associated with an increased risk of MI but not with an increased risk of CVA . === Medicine, Faculty of === Medicine, Department of === Experimental Medicine, Division of === Graduate
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