Background/Purpose: Cardiovascular disease is highly prevalent in Rheumatoid Arthritis (RA) and in non-RA subjects with low vitamin D levels. The aim of the present study was to evaluate the long-term risk of serious cardiovascular events (SCVE) RA patients having low vitamin D at time of diagnosis, compared to patients with normal vitamin D levels at RA diagnosis.

Methods: The study is a longitudinal observational study with retrospective evaluation of outcomes using patient record adjudication, based on post-hoc evaluation of an Investigator-Initiated, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study: The CIMESTRA Study (NCT00209859). Patients were recruited at 4 Danish University Clinics from October 1999 to October 2002: 160 early diagnosed, DMARD- and steroid RA-patients, fulfilling ACR 1987 criteria for RA were included in the original CIMESTRA study (NCT00209859). Eligibility criteria excluded most co-morbidities. The original CIMESTRA study treated all patients with methotrexate and intra-articular steroid, aiming at remission. Patients were further randomized to ciclosporine or placebo. Self-reported vitamin D intake was evaluated, and vitamin D supplemented according to national Danish Guidelines.

One-hundred-fifty-eight patients had vitamin D metabolites measured at time of diagnosis, prior to initiation of treatment and eventual vitamin D supplementation, and were included in the current study: Patients were allocated according to serum D_total (the sum of 25OHD₂ and 25OHD₃) at time of diagnosis, comparing  “low” = D_total < 50 nmol/l to “normal” = D_total ≥ 50 nmol/l. One-hundred-forty-two patients were alive without missing data for journal-adjudications after 10 years of follow-up. Primary outcome was a composite of fatal and non-fatal SCVEs. Secondary outcomes were cardiovascular mortality and all-cause mortality. All events were evaluated through patient-record adjudication, using a validated adjudication process (See figure 1).

Odds for SCVE were evaluated using multiple logistic regression, adjusted for original trial group-allocation (ciclosporine or placebo), Trial Center, and the pre-specified, potential confounding variables sex, age at time of diagnosis, smoking, adipositas and ACPA-status, whereas the fully adjusted model further included weight and 1,25(OH)₂D, both being statistical significant associated with D_total-status at time of diagnosis.

Results: Overall 10-year SCVE incidence was lower than expected (13.9% in patients with low D_total, 14.3% in patients with normal D_total) (See figure 2). There were no difference in SCVE between D_total groups in crude analysis OR=0.91, 95%CI (0.4; 2.3), or in fully adjusted model: OR=0.86, 95%CI (0.2; 3.2) (See table 1) Survival analyses showed no difference in SCVE according to baseline D_total, HR=1.15, 95 % CI (0.6; 2.3).

Conclusion: The 10-year SCVE incidence of 13.9% was unexpectedly low. Low vitamin D status at time of RA diagnosis was not associated with long-term SCVE in early diagnosed, aggressively controlled and DMARD treated RA patients.

Figure 1 – SCVE adjudication CIMESTRA CVD

Figure 2 – Kaplan-Meier-plot – observed vs expected SCVE

Table 1 – Results of logistic regression

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/are-vitamin-d-metabolite-levels-at-time-of-diagnosis-associated-with-long-term-severe-cardiovascular-events-in-early-diagnosed-rheumatoid-arthritis-patients-aggressively-treated-during-10-year-follow/