Original Article

Screening for Connective Tissue Disease in Pulmonary Arterial Hypertension

Authors: Ricardo J. Pagán, MD, Augustine S. Lee, MD, Christopher O. Austin, MD, Charles D. Burger, MD


Objectives: 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).

Methods: 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.

Results: 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%.

Conclusions: 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.

This content is limited to qualifying members.

Existing members, please login first.

If you have an existing account please login now to access this article or view your purchase options.

Purchase only this article ($15)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.


1. Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013;62:D34-41.
2. Benza RL, Gomberg-Maitland M, Miller DP, et al. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest 2012;141:354-362.
3. Chung L, Liu J, Parsons L, et al. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest 2010;138:1383-1394.
4. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol 2009;53:1573-1619.
5. Vazquez AA, Aduen JF, Aduen P, et al. Should all patients with pulmonary hypertension undergo HIV serologic testing? South Med J 2011;104:589-592.
6. Alpert MA, Goldberg SH, Singsen BH, et al. Cardiovascular manifestations of mixed connective tissue disease in adults. Circulation 1983;68:1182-1193.
7. Condliffe R, Kiely DG, Peacock AJ, et al. Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am J Respir Crit Care Med 2009;179:151-157.
8. Kamel SR, Omar GM, Darwish AF, et al. Asymptomatic pulmonary hypertension in systemic lupus erythematosus. Clin Med Insights Arthritis Musculoskelet Disord 2011;4:77-86.
9. Lambova S, Muller-Ladner U. Pulmonary arterial hypertension in systemic sclerosis. Autoimmun Rev 2010;9:761-770.
10. Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest 2010;137:376-387.