Endothelial Biomarkers of Systemic Sclerosis‐Associated Pulmonary Hypertension

Abstract

ObjectiveDespite efforts at early detection, patients with systemic sclerosis (SSc) pulmonary hypertension (PH) present with advanced disease. We sought to determine whether endothelial biomarkers (asymmetric dimethylarginine [ADMA], soluble endoglin [sEng], and pentraxin‐3 [PTX‐3]) can determine SSc‐PH risk or differentiate between SSc‐PH subgroups.MethodsADMA, sEng, and PTX‐3 were measured by enzyme‐linked immunosorbent assay in four groups: 1) 18 healthy controls, 2) 74 patients with SSc‐PH, 3) 44 patients at high risk for PH features, and 4) 10 patients with low risk for PH features. High‐risk features included a diffusion capacity (DLco) less than 55% with a forced vital capacity (FVC) greater than 70%, an FVC/DLco ratio of >1.6, or a right ventricular systolic pressure on an echocardiogram greater than or equal to 40 mm Hg. ADMA, sEng, and PTX‐3 were compared between these four groups as well as stratified based on the three SSc‐PH clinical classification groups (pulmonary arterial hypertension [PAH], left‐heart disease, and interstitial lung disease [ILD]).ResultsPTX‐3 was significantly lower in subjects with SSc at low risk for PH (median 27.0 pg/ml [interquartile range (IQR) 19.0–47.3]; P < 0.003) than the other groups. The area under the receiver operating characteristic curve was 0.87 (95% confidence interval 0.76–0.98, P = 0.0002) to differentiate low risk from high risk for patients with PH. PTX‐3 was significantly lower in SSc‐PH from disease of the left side of the heart (57.5 pg/ml [IQR 39.8–79.0]; P < 0.01) compared to SSc‐PH from either PAH (85.5 pg/ml [IQR 56.3–104.5]) or ILD (90.3 pg/ml [IQR 74.9–111.0]). Neither ADMA nor sEng differed between the four groups.ConclusionPTX‐3 is a promising biomarker of PH risk status in patients with SSc as well as a possible marker of precapillary PH, which should be validated in an external cohort.image