Rheumatoid Arthritis and Cardiovascular Mortality

Rheumatoid arthritis (RA) has long been associated with elevated mortality and morbidity. Patients with RA have significantly higher rates than the overall population of ischemic heart disease, atherosclerosis, peripheral vascular disease, congestive heart failure, cerebrovascular disease, type 2 diabetes, hyperlipidemia, and hypertension.^1-3 Not surprisingly, patients with RA also have higher usage rates of ACE inhibitors, calcium channel blockers, diuretics, nitrate/vasodilators, anticoagulants, and antihyperlipidemia agents than do individuals in the general population.¹

A recent meta-analysis demonstrated that RA is associated with an increased risk of cardiovascular death (standardized mortality rate [SMR] of 1.5) relative to the general population.³ This was largely accounted for by increased mortality rates of ischemic heart disease and cerebrovascular accidents (SMR of 1.59 and 1.52, respectively). The clinical patterns of cardiovascular disease seen in patients with RA do not mimic those seen in the overall population, with RA patients experiencing silent myocardial infarctions and sudden death at approximately twice the frequency than their control counterparts.²

Although independent risk factors such as family history and smoking may contribute to the increased risk of cardiovascular disease in RA patients, current evidence suggests shared mechanisms between the inflammation associated with RA and the associated increased risk of cardiovascular mortality. For instance, the pathogenesis of atherosclerosis has been linked to many of the proinflammatory cytokines released by joints affected by RA, including tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, and interferon (IFN)-γ (Figure 1).⁴

The link between RA and inflammation leading to cardiovascular mortality highlights the need to appropriately assess cardiovascular risk factors in patients with RA and the potential benefits of minimizing inflammation in patients with RA. Further research is needed, but some studies suggest that statins may have a role in reducing lipid levels and modulating inflammation and joint symptoms in patients with RA.⁵ Additionally, some antirheumatic therapies such as cyclooxegenase (COX) inhibitors and TNF inhibitors may influence cardiovascular disease risk.^2,5

Practice Points

• Patients with RA have increased cardiovascular mortality rates and higher rates of ischemic heart disease
• Chronic inflammatory processes likely account for the association between RA severity and cardiovascular disease
• Treatments that target inflammation may reduce risk of cardiovascular mortality in patients with RA

Figure 1. Shared inflammatory pathways between rheumatoid arthritis and atherosclerosis.⁴
Reprinted from Am J Med 121. Libby P. Role of inflammation in atherosclerosis associated with rheumatoid arthritis, S21-S31. Copyright 2008, with permission from Elsevier.

PAI-1, plasminogen activator inhibitor–1; CRP, C-reactive protein; IFN, interferon

References

1. Han C, Robinson DW, Jr., Hackett MV, et al. Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol. 2006;33:2167-2172.
2. Gabriel SE. Cardiovascular morbidity and mortality in rheumatoid arthritis. Am J Med. 2008;121:S9-14.
3. vina-Zubieta JA, Choi HK, Sadatsafavi M, et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008;59:1690-1697.
4. Libby P. Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am J Med. 2008;121:S21-S31.
5. Turesson C, Jacobsson LT, Matteson EL. Cardiovascular co-morbidity in rheumatic diseases. Vasc Health Risk Manag. 2008;4:605-614.