Background/Purpose:

Increased risk of cardiovascular disease (CVD) and premature mortality in rheumatoid arthritis (RA) has been established, but the impact of inflammatory and disease related factors has been inconsistent across studies.

Here, we determined if occurrence of subsequent CVD and mortality outcomes was influenced by disease related factors at RA onset and the first years of disease, and if the impact of these factors differed between age groups. Further we investigated the role of antibodies against phosporylcholine (anti-PC), a promising atheroprotective biomarker.

Methods:

This is a cohort study derived from the BARFOT inception RA cohort, to which patients were consecutively recruited from 1994 through 1999, disease duration <13 months. Participants with prevalent CVD at study enrollment or aged <20 years were excluded. The outcomes were an incident CVD event (myocardial infarction, cardiac arrest, angina pectoris, peripheral arterial disease, coronary or vascular surgery, stroke and transient ischemic attack) and all-cause mortality, and were tracked through the Swedish Hospital Discharge Registry and the National Cause of Death Registry until December 2010.

Area under the curve (AUC) was calculated for disease measures assessed at inclusion and after 1 and 2 years, and differences (D) between inclusion and 1 year after enrollment. IgM anti-PC was determined by ELISA.

Cox proportional regression models in age groups <65 and ≥65 years at RA onset, adjusted for age, gender, smoking, presence of hypertension, diabetes or hyperlipidemia, and Kaplan Meier analysis were used for statistical tests.

Results:

The study population comprised 741 patients with early RA, whose mean age at entry was 55 years (SD 14.7), range 20-93 years, 67.5% of the participants were women, and 60% were RF positive. The median observation was 13 years (range 2-17). During follow-up, 177 patients developed an incident CVD event, and 151 deceased, corresponding rates of 2.1 (1.8-2.4) and 1.7 (1.4-1.9) per 100 person-years.

Only in the younger individuals, RF or ACPA positivity, CRP-AUC, ESR-AUC, and VAS pain-AUC were associated with higher risk of CVD event, adjusted hazard ratios (HRs) 2.72 (95% CI, 1.48-5.02), 1.87 (1.01-3.34), 1.07 (1.01-1.14), 1.10 (1.02-1.17), and 1.06 (1.00-1.13), respectively. On the other hand, only in the older patients, DCRP, DESR, DHAQ, and also regular use of methotrexate and daily oral glucocorticoids were associated with incident CVD, respective HRs 0.94 (0.89-1.00), 0.90 (0.82-0.97), 0.71 /0.52-0.97), 0.64 (0.43-0.96), and 1.69 (1.13-2.51). Similarly, RF or ACPA positivity and VAS pain-AUC were associated with higher death risk in the younger patients, while CRP-AUC, ESR-AUC and HAQ-AUC were independently related to risk of death in both age groups.

CVD outcome but not mortality was associated with the levels of anti-PC at baseline, the 10-year CVD event-free survival rates were 66%, 74% and 76% in the first (lowest), second and third anti-PC tertiles, respectively, p=0.024.

Conclusion:

In early RA, age stratification could improve evaluation of risk factors for CVD and mortality. The IgM anti-PC antibodies may perform atheroprotective in RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/age-specific-association-between-disease-related-measures-and-incident-cardiovascular-events-and-all-cause-mortality-in-early-rheumatoid-arthritis/