Background/Purpose:

Rheumatoid arthritis (RA) is associated with an increased rate of cardiovascular (CV) disease. Systemic inflammation has been implicated as a key factor behind CV comorbidity in RA. The objective of this study was to investigate the impact of disease activity and inflammation over the first two years on the risk of subsequent CV events in patients with early RA.

Methods:

An inception cohort of patients with early RA (symptom duration <12 months), recruited in 1995-2005 from a defined area, was investigated. Patients were followed according to a structured program, with follow-up visit at 6, 12 and 24 months after inclusion. The clinical examinations were performed by the same rheumatologist.  Those included in the study were managed according to usual care, with no pre-specified protocol for anti-rheumatic treatment or CV prevention. Patients with a 24-month visit in 1998 or later were included in the present analysis. Data on CV events (hospitalization or out-patient visit due to coronary artery disease, cerebrovascular disease or peripheral artery disease) during the period 1998-2011, based on diagnostic codes, were retrieved from a regional health care register. Traditional CV risk factors were investigated in a structured review of the medical records. Cox regression models were used to assess associations between the area under the curve (AUC) for disease activity parameters over the first two years, and CV events occurring later during the disease course. Furthermore, the impact of disease activity parameters at the 2-year follow-up were assessed in separate models. Since the assay for CRP was modified to a high-sensitivity analysis during the study period, the AUC for CRP could not be calculated. CRP was therefore modelled as a dichotomized variable (above vs. below the 75^th percentile at 2 years).

Results:

A total of 207 patients with early RA (70 % women, mean age 62 years) were followed from the 24-month visit to the first CV event, migration from the region, death or Dec 31, 2011. CV events occurred in 54 patients during the follow-up.  A high disease activity over the first two years (defined as AUC for DAS28 above the median) was associated with a significantly increased risk of CV events (age-sex adjusted hazard ratio (HR) 2.03; 95 % confidence interval (CI) 1.15-3.60).  In separate analyses, it was demonstrated that patients with CRP at two years within the highest quartile (>11 mg/l) had a significantly higher risk of CV events compared to those with lower CRP values (age-sex adjusted HR 1.82; 95 % CI 1.04-3.17). Results were similar in models adjusted for smoking, hypertension and diabetes in addition to age and sex (multivariate adjusted HRs for DAS28-AUC above the median:  2.05 (95% CI 1.13-3.73); for CRP>11 mg/l: 1.90 (95% CI 1.06-3.42)).

Conclusion:

A high disease activity during the first two years after RA diagnosis and a high CRP at the two-year follow-up were both associated with a doubled risk of CV events. These findings suggest that patients with persistently active RA are at particularly increased risk, and highlight the importance of disease control for CV prevention in patients with early RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/high-disease-activity-over-time-and-persistent-inflammation-are-associated-with-increased-risk-of-cardiovascular-disease-in-patients-with-early-rheumatoid-arthritis/