Though it is apparent that RA patients are at increased risk of developing CV disease and that this contributes to the increased mortality observed in the RA population, the factors responsible for this increased CV disease are unclear. Therefore, we investigated the relative contribution of traditional risk factors (such as smoking and hypertension), measures of inflammation associated with RA, and RA treatments to the increased risk of CV disease and mortality observed in RA.
In the Rochester RA cohort, a number of traditional risk factors for CV disease were found to contribute to CV death. These included a personal history of ischemic heart disease, smoking, hypertension, and diabetes mellitus.15
Solomon et al30
reported an overall similar pattern of CV risk factors in a population of women with RA compared with women without RA. Our findings agree with these, in general, but we also observed some significant differences in the distribution of these risk factors between the 2 groups.18
During follow-up, RA patients were more likely to have low body mass index (BMI) (rate ratio [RR], 1.8; 95% CI, 1.3–2.5) and alcohol abuse (RR, 3.3; 95% CI, 1.7–7.6) but less likely to have dyslipidemia (RR, 0.8; 95% CI, 0.6–0.9). In addition, the CV risk factors in RA patients did not appear sufficient to explain the increased risk of CV death in RA patients. The proportion of the risk of congestive heart failure that could be attributed to CV risk factors and ischemic heart disease was significantly lower in RA patients than in non-RA patients (54% vs 77% at an age of 80 y).13
Systemic inflammation associated with rheumatoid disease appears to account for a large proportion of this unexplained risk of CV death in the RA population. After adjustment for demographics, traditional CV risk factors, and comorbidities, we found that higher erythrocyte sedimentation rate (ESR), small and large joint swelling, rheumatoid nodules, vasculitis, and RA lung disease were all independently associated with an increased risk of CV death.15
In RA patients who experienced new-onset heart failure, the proportion of patients with very high ESR values (≥40 mm/h) was greatest in the 6 months immediately preceding heart failure.31
These findings suggest that ESR, a marker of systemic inflammation, signals the onset of heart failure in persons with RA. These results are consistent with previous reports that have demonstrated an association between markers of systemic inflammation (including joint swelling32
) and the risk of mortality in RA.
Assessment of the effect of RA medications on CV outcomes is complicated by the potential for confounding by indications and contraindications of the respective treatments. Therefore, their contribution to CV mortality is controversial. It has been suggested that treatment with corticosteroids may promote premature atherosclerosis and CV disease in RA patients.34
In our RA cohort, we observed an increased risk of CV events in RF+ RA patients with high cumulative exposure to corticosteroids (>7000 mg; HR, 3.06; 95% CI, 1.81–5.18).35
In contrast, RF– RA patients with high cumulative exposure to corticosteroids were not at increased risk of CV events (HR, 0.85; 95% CI, 0.39–1.87). However, in RA patients with a personal history of ischemic heart disease, treatment with corticosteroids was found to attenuate the risk of CV death.15
Use of methotrexate may also alter the risk of CV death in RA, although the nature of the effect is, at present, unclear. In one frequently cited study, use of methotrexate was found to be associated with a reduced risk of CV death (HR, 0.3; 95% CI, 0.2–0.7), after adjustment for indication.36
Consistent with these data, treatment with methotrexate has also been associated with reduced vascular disease in RA patients (HR, 0.83; 95% CI, 0.71–0.96).37
However, in another study using similar analysis techniques, use of methotrexate in patients with CV disease was associated with marked and significant increase in mortality (HR, 3.40; P
Thus,more research is needed to fully understand the impact of disease modifying anti-rheumatic drugs on CV risk.39,40