Background/Purpose: Pulmonary hypertension (PH) is a disease entity characterized by elevated pulmonary artery pressure, which often results in right ventricular failure. As part of PH evaluation, anti-cyclic citrullinated protein antibody (ACPA) titers are intermittently checked. However, data regarding presence and clinical significance of elevated ACPA titers is unavailable.

Methods: A retrospective analysis of patients from 12/1/2006 to 12/31^/2016 was completed at a single tertiary center.  Patients with a diagnosis of PH, based on right heart catheterization and/or evaluation by a pulmonologist and consistent echocardiogram, in whom ACPA levels were obtained were included. Patients with RA and connective tissue disease (CTD), including SSc, SLE, MCTD, UCTD, PM, DM, Sjogren’s disease, Overlap and antisynthetase syndrome were identified based on a clinical  diagnosis by a rheumatologist. P values were computed using Fishers exact test.   

Results: A total of 263 charts were reviewed; 106 patients were confirmed to have PH and had ACPA measured. Of these patients, 21 (19.8%) were ACPA positive and 85 (80.2%) were ACPA negative.

Of the 21 patients who were ACPA positive, 15 (71%) had a concomitant diagnosis of RA and PH;  the diagnosis of RA preceded the diagnosis of PH in 7 patients (46.7%); followed by PH preceding the diagnosis of RA in 5 (33.3%); and a concurrent diagnosis was made in 3 (20%).

Similarly, of 85 ACPA negative patients, a concomitant diagnosis of RA and PH was made in 7 (8.2%); the diagnosis of RA preceded the diagnosis of PH in 3 (42.8%); a concurrent diagnosis of PH and RA was seen in 3 (42.8%), followed by a diagnosis of PH preceding the diagnosis of RA in 1 (14.4%).

In the 15 patients who were ACPA positive and had RA, 5 (33%) also had a diagnosis of interstitial lung disease (ILD).  Of those who were ACPA negative and had RA, 3 of 7 (42.9%) had ILD (p=1).

Among ACPA positive patients (21) only 4 had a diagnosis of CTD along with RA as compared to the ACPA negative group of 85 patients of whom 44 (51.8%) had CTD alone and 3 had CTD with RA (47, 55.2%) (p=0.003).  

The ACPA positive patients (7/21, 33.3%) had similar mortality compared to the ACPA negative patients (26/85, 30%) and ACPA positivity was not associated with an increased risk of death (p=0.79).

Conclusion: In a cohort of patients with PH who had ACPA levels obtained, 20% were positive.  In majority of both ACPA positive and ACPA negative patients, the diagnosis of RA preceded or was made concurrently with the diagnosis of PH. However, the diagnosis of PH preceded that of RA in a relatively higher percentage of ACPA positive patients compared to ACPA negative patients. Interestingly, about 30% of ACPA positive patients with PH did not develop RA over the course of the follow-up.  The link between positive ACPA and PH is not explained by ILD in isolation. Further data is required to understand the prognostic implications of the presence of ACPA in patients with PH.