Anti-TNFs Have Not Leveled Cardiovascular Risk in RA



WASHINGTON – The advent of effective anti-inflammatory therapies and the increased use of cardioprotective therapies in recent years have failed to reduce the risk of incident cardiovascular disease in patients with rheumatoid arthritis, according to findings from the prospective longitudinal CARRE study.

During the 10-year Dutch study, 58 cardiovascular events occurred in 353 patients with more than 2,361 patient-years of follow-up, for an incidence rate of 25.3/1,000 patient-years. This did not differ significantly from the incidence rate of 22.8/1,000 patient-years between 3 years and 10 years of follow-up, Dr. Alper M. van Sijl reported at the annual meeting of the American College of Rheumatology.

Nonetheless, the findings do suggest that improving disease activity and inflammatory markers over time might mitigate cardiovascular risk, said Dr. van Sijl of the Jan van Breemen Research Institute, Reade, Amsterdam.

Patients with RA have a twofold increase in the risk of mortality compared with the general population, and this is largely attributable to cardiovascular disease, he said, noting that it has been unclear what role cardiovascular risk factors vs. the underlying inflammatory processes of RA play in this.

"Most research only accounts for cardiovascular risk factors at baseline, and does not look at longitudinal data," he said.

To evaluate whether the increased use of anti-inflammatory and cardioprotective medications has reduced the risk, Dr. van Sijl and his colleagues compared changes in cardiovascular risk factors, RA-related factors, and medication use over time based on whether study participants did or did not develop cardiovascular disease during follow-up. The investigators found that general cardiovascular risk increased over time, as did the use of antihypertensives, statins, and tumor necrosis factor inhibitors, while RA-related factors improved significantly over time.

For example, with respect to cardiovascular disease risk, changes in markers such as intima-media thickness and cardiovascular risk score were seen. Intima-media thickness increased by 0.030 mm between baseline and 3-year follow-up, and decreased by 0.006 mm between 3 and 10 years. Ten-year CV risk (SCORE) increased by 0.5 points between baseline and 3-year follow-up, and by 4.4 points between 3 and 10 years. Antihypertensive use increased by 4% and 11% during the same periods (from 24% at baseline), respectively; statin use increased by 3% and 5% (from 9% at baseline) during the same periods; and use of biologic agents increased 9% and 14% (from 2% at baseline).

As for RA-related factors, improvements were seen in erythrocyte sedimentation rate in those who did not develop cardiovascular disease, while the rate increased in those who did develop cardiovascular disease. Similarly, disease activity scores (DAS28) improved in both groups between baseline and 3 years, then increased between the assessment done at 3 and that done at 10 years in those who developed cardiovascular disease, while they continued to decrease in those who did not.

The use of biologics increased significantly more over time in those without cardiovascular disease, compared with those with cardiovascular disease (to about 35% vs. 15%).

Generalized estimating equation analysis demonstrated a positive association between the use of tumor necrosis factor inhibitors and a reduction in incident cardiovascular disease, Dr. van Sijl said.

The findings suggest that more aggressive cardioprotective and anti-inflammatory treatment might mitigate the burden of cardiovascular disease in patients with RA, he said.

CARRE study participants were enrolled beginning in 2000. All fulfilled ACR 1987 criteria for RA, and had a mean disease duration of 7 years. Most were women in their 60s with high levels of disease activity, Dr. van Sijl said.

"In summary, the risk of incident cardiovascular disease persists in RA despite incremental use of cardioprotective medication and/or TNF blocking agents. At baseline, cardiovascular risk factors such as blood pressure and renal function were more associated with incident cardiovascular disease than RA-related factors, and changes in RA-related factors during follow-up were associated with an increased risk of incident cardiovascular disease," he said. Although traditional cardiovascular risk factors remain relevant in the risk of cardiovascular disease in RA patients, improving disease activity and inflammatory markers over time might positively influence this risk, he added.

Dr. van Sijl reported having no disclosures.

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