Background/Purpose: People with rheumatoid arthritis (RA) suffer an excess burden of cardiovascular disease (CVD), yet standard risk assessments designed for the general population do not accurately predict their CVD risk. The purpose of this study was to identify traditional CVD risk factors that have a significantly different impact on CVD development in the presence of RA. Recognition of potentially distinctive contributions of CVD risk factors in RA could inform the development of improved CVD risk assessment tools for patient management.

Methods: A population-based inception cohort of RA subjects aged ≥30 years who fulfilled 1987 ACR criteria for RA between 1-1-1988 and 1-1-2008 was assembled and followed until death, migration, or 12-31-2008. Medical records were reviewed to ascertain the presence of CVD risk factors (age, blood pressure, lipids, smoking, and diabetes mellitus) at RA incidence and to ascertain the development of CVD (myocardial infarction, CVD death, angina, heart failure, stroke and intermittent claudication) during follow-up. The 10-year Framingham risk score (FRS) for CVD was calculated. Cox models were used to examine the effects of CVD risk factors included in the FRS in patients with RA, and whether RA disease characteristics (e.g., rheumatoid factor [RF] positivity, acute phase reactants, extra-articular manifestations) modify the effects of CVD risk factors. Models were adjusted for the FRS and stratified by sex.

Results: The study included 525 patients with RA without prior CVD (mean age: 55 years, 71% women; 68% RF positive). The patients were followed for a mean of 8.4 years, during which 84 developed CVD (47 women, 37 men). The FRS predicted only 45.7 events (23.3 women, 22.4 men). Essentially all of the excess events (37.2 of 38.3) were among the RF-positive patients. Analysis of CVD risk factors revealed a greater effect of age on the risk of developing CVD among RF-positive but not RF-negative patients.  As estimated by the FRS, the effect of age on CVD risk in the RF-positive group was nearly double its effect in the general population (p<0.001). The impact of this additional aging effect was negligible for patients younger than 50 years, when CVD risk in the general population is generally low. However, the impact was observed to increase exponentially as CVD risk rose with age. For example, patients over 65 years with RF-positive RA had similar CVD risk as persons in the general population aged >90 years. The unique influence of age in RF-positive RA was not explained by other CVD risk factors or RA disease characteristics. Acute phase reactants and severe extra-articular manifestations also appear to influence CVD risk in RF positive RA after accounting for this additional age effect.

Conclusion: The results revealed an exponentially increasing effect of age on CVD risk in patients who have seropositive RA, supporting prior reports of accelerated aging in this disease. In contrast, the impact of age on CVD risk among RF-negative patients was similar to the general population.  These findings suggest that the advent of CVD risk scores that better account for accelerated aging and other factors in RF-positive patients could improve CVD risk assessment for persons with RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/accelerated-aging-influences-cardiovascular-disease-risk-in-rheumatoid-arthritis/