Comorbidities Associated With RA

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RA reduces a patient's average life expectancy by 5 to 10 years, but RA alone rarely 11 12

causes death. ' Instead, specific comorbidities contribute to premature death independent of safety issues surrounding the use of immunomodulating medications.

O The comorbidities with the greatest impact on morbidity and mortality associated with RA are: (a) cardiovascular disease; (b) infections; (c) malignancy; and (d) osteoporosis.11' 2

Cardiovascular Disease

Half of all deaths in RA patients are cardiovascular related.11 Because a patient with

RA experiences inflammation and swelling in his or her joints, it is likely that there is inflammation elsewhere, such as in the blood vessels, termed vasculitis. C-reactive protein (CRP), a nonspecific marker of inflammation, is associated with an increased risk of cardiovascular disease; CRP is elevated in patients with RA. Chronic systemic inflammation may contribute to the relationship between RA and cardiovascular dis-


ease, but the exact mechanism is still under investigation. ' Uncontrolled hypertension is common in patients with RA. Clinicians should screen for and aggressively

treat elevated blood pressure in this population. Infections

RA itself leads to changes in cellular immunity and causes a disproportionate increase

in pulmonary infection and sepsis. Because medications that alter the immune system are linked to an increased risk of infection, it is difficult to distinguish between an increased risk of infection secondary to RA and the medications used to treat RA.

Patients and clinicians must pay close attention to signs and symptoms of infection

because of this increased risk.


Patients with RA have an increased risk of developing lymphoproliferative malignancy (e.g., lymphoma, leukemia, and multiple myeloma) and a decreased risk of developing cancer of the digestive tract.12,14,1 The relationship between RA and cancer is not clear. To confound the issue, medications for the treatment of RA may contribute to increased cancer risk. Patients presenting with new onset of symptoms (e.g., fevers, night sweats, chills, or anorexia) out of proportion with disease activity and patients not responding to conventional RA treatment should be evaluated further for lymphoproliferative malignancy.12,15


Osteoporosis associated with RA follows a multifaceted pathogenesis, but the primary mechanism likely is mediated by increased osteoclast activity.12 The cytokines involved in the inflammatory process directly stimulate osteoclast and inhibit osteoblast activity. Additionally, arthritis medications can lead to increased bone loss. Bone mineral density should be evaluated at baseline and routinely using dual-energy x-ray absorptiometry. 12

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