Factors associated with pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc)

Abstract

Background: Pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) is a lethal complication affecting 8-15% of patients. Screening tests such as echocardiography and pulmonary function tests allow for triaging patients for diagnosis by right heart catheterization. Understanding risk factors of SSc-PAH could help differentiate high-risk patients.

Methods: A systematic review was conducted to determine associations with SSc-PAH, including clinical/disease characteristics, antibodies, labs and biomarkers. The frequencies of publications featuring each risk/association were reported.

Results: Among 2654 articles, 984 duplicates and 1578 irrelevant articles were removed, leaving 92 articles for manual screening. After excluding 55 papers with small sample sizes, publications from identical cohorts, not English language, or PAH not ascertained by RHC, 37 articles were eligible. A total of 43 factors for SSc-PAH were identified within seven categories. Several associations were due to PAH and risk factors such as dynpnea, right heart failure, and short 6-minute walk distance. Patient characteristics (14), pulmonary physiology (6), antibody profiles (6) and genetics/epigenetics (6) had the most numerous and diverse factors, while biomarkers (4) and other labs (2) features were infrequent. Low carbon monoxide (DLCO) (6), older age (4), longer disease duration (4), positive anticentromere antibodies (ACA) (4), telangiectasias (4), high brain natriuretic peptide (4) were frequent associations.

Conclusions: Risk factors for SSc-PAH such as ACA, older age, longer disease duration limited cutaneous SSc subset and presence of ILD may enrich screening programs. Genes and other antibody profiles are inconsistent and requires further validation.