Endothelial Biomarkers of Systemic Sclerosis-Associated Pulmonary Hypertension
Arthritis Care and Research
Objective: Despite 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. Methods: ADMA, 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]). Results: PTX-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. Conclusion: PTX-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. (Figure presented.).
Lammi, Matthew R.; Kolstad, Kathleen D.; Saketkoo, Lesley Ann; Khatri, Avani; Utz, Paul J.; Steen, Virginia D.; and Chung, Lorinda, "Endothelial Biomarkers of Systemic Sclerosis-Associated Pulmonary Hypertension" (2023). School of Medicine Faculty Publications. 1457.