Screening for connective tissue disease in pulmonary arterial hypertension

To evaluate the utility of anti-nuclear antibody (ANA) levels in distinguishing the cause of pulmonary arterial hypertension as idiopathic (IPAH) or connective tissue disease related (CTD-PAH).

We retrospectively identified patients with IPAH or CTD-PAH seen between 2010 and 2012 at our institution. Medical records were reviewed for demographic and clinical data and laboratory values.

Of 115 patients identified, 65 (56%) had IPAH and 50 (44%) had CTD-PAH. The mean age was 59 years and most of the patients (76%) were women. Most patients (64%) were in World Health Organization functional class III or IV. Compared with the IPAH group, the CTD-PAH group had significantly increased B-type natriuretic peptide levels (635 vs 325 pg/mL; P = 0.02) and decreased pulmonary vascular resistance (6 vs 9 WU; P = 0.04). The median ANA level was significantly higher in the CTD-PAH group than the IPAH group (7 vs 0 U; P < 0.001). The area under the receiver operating characteristic curve for a positive ANA to predict CTD-PAH was 0.91 (P < 0.001). A cutoff of 5 U for predicting ANA provided an optimal specificity of 94% and a sensitivity of 70%. The resulting likelihood ratio using the same cutoff was 12 (P < 0.001), or a positive predictive value of 91% with a negative predictive value of 79%.

In this selected cohort of patients, a quantitative ANA value >5 U may be useful in distinguishing CTD-PAH from IPAH, but a lower level does not confidently exclude CTD-PAH.