Cardiovascular Morbidity and Mortality in Rheumatoid Arthritis

https://doi.org/10.1016/j.amjmed.2008.06.011Get rights and content

Abstract

Patients with rheumatoid arthritis (RA) are at increased risk of mortality compared with the general population. Evidence suggests that this increased mortality can largely be attributed to increased cardiovascular (CV) death. In a retrospective study of an inception cohort of RA patients in Rochester, MN, we found that patients with RA were at increased risk of CV death, ischemic heart disease, and heart failure compared with age- and sex-matched community controls. In addition, when we examined coronary artery tissue from autopsied RA patients, we observed increased evidence of inflammation and an increased proportion of unstable plaques. We also investigated the contribution of traditional and RA-specific risk factors to this increased risk of CV morbidity and mortality. Although traditional CV disease risk factors were found to contribute to the increased risk of mortality in RA patients, they did not fully explain the increased CV mortality observed in RA. Instead, increased inflammation associated with RA appears to contribute substantially to the increased CV mortality. Together with other studies that have demonstrated similar associations between RA and CV mortality, these data suggest that more aggressive management of inflammation in RA may lead to significant improvements in outcomes for patients with RA.

Introduction

Many studies, dating back more than 50 years, have reported an increased risk of mortality in patients with rheumatoid arthritis (RA).1, 2, 3, 4, 5 Recent evidence has demonstrated that this increased risk may be largely attributable to cardiovascular (CV) events.6, 7, 8, 9 Although it has been previously reported that CV morbidity and mortality are increased in RA, it has been unclear whether the pattern of CV disease is similar in patients with and without RA. Furthermore, the contribution of traditional risk factors, RA disease characteristics, and RA treatments to this mortality has been uncertain. In particular, given the recent appreciation of the important role of inflammatory processes in the development and progression of atherosclerosis,10 interest has focused on the CV risk that might be associated with systemic inflammation in RA. This review will focus on studies investigating these questions conducted using the Rochester Epidemiology Project and will compare data obtained in these studies with other published literature. Additionally, the implications of these findings for the management of inflammation in RA will be discussed.

Section snippets

Study design

The Rochester Epidemiology Project is a data resource that is ideally suited to the population-based investigation of long-term outcomes in RA. Its data linkage system provides access to the Mayo Clinic unified medical record system, and the complete (inpatient and outpatient) medical records of all healthcare providers in Olmsted County, MN are captured.11 Consequently, virtually every case of RA fulfilling American College of Rheumatology (ACR) diagnostic criteria in the local population is

Cardiovascular Death

Data from the Rochester Epidemiology Project have confirmed and extended previous studies that demonstrated an increased mortality in individuals with RA. Overall, patients in the RA cohort were found to have a markedly increased risk of death compared with the general population. Between 1955 and 1994, patients in the RA cohort had a significantly increased risk of death compared with age- and sex-matched controls (P < 0.001; standardized mortality ratio [SMR], 1.27; 95% confidence interval

Risk factors for cardiovascular disease in rheumatoid arthritis

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

Conclusions

In summary, we observed a significantly increased risk of overall mortality, CV death, ischemic heart disease, and heart failure compared with the general population in a population-based incidence cohort of RA patients followed up for approximately 15 years. The overall mortality gap between RA patients and the general population is not closing. Indeed, it appears to be widening. In addition to the increased prevalence of CV mortality in the RA population, the pattern of CV disease in this

Author disclosures

  • Sherine E. Gabriel, MD, has no financial arrangement or affiliation with a corporate organization or a manufacturer of a product discussed in the supplement.

Acknowledgment

The author would like to thank Ali Hassan, PhD, for assistance in drafting this manuscript.

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    This work was supported by grants from the National Institutes of Health: R01 AR46849 and AR-30582.

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