The Utility of Plasma Vascular Biomarkers in Systemic Sclerosis: A Prospective Longitudinal Analysis.

Publication date: Mar 21, 2020

Pulmonary hypertension (PH) and ischemic digital lesions (DL) are two scleroderma vascular outcomes that in cross-sectional studies are associated with abnormalities in biomarkers of angiogenesis. The clinical usefulness of these biomarkers is unknown in part due to lack of data on longitudinal measurement.

We conducted a prospective cohort study of 300 patients with systemic sclerosis (SSc) who were followed for at least a five-year period, who at enrollment lacked evidence of PH and/or active DL. Levels of hepatocyte growth factor (HGF), soluble Flt-1, soluble endoglin, endostatin, and platelet-derived growth factor (PlGF) were obtained at multiple time points and assessed for their ability to predict the development of PH/DL.

46 patients (15%) developed PH and 69 (23%) developed a DL. In time-to-event analyses, three biomarkers measured at cohort entry were found to significantly associate with the development of PH: HGF (HR 1.99, 95%CI 1.24-3.17, p=0.004), sFlt1 (HR 3.04, 95%CI 1.29-7.14, p=0.011), and PlGF (HR 2.74, 95%CI 1.32-5.69, p=0.007). As time approaching PH diagnosis decreased, there was no corresponding increase in any biomarker level. Upon converting each continuous vascular biomarker into a binary variable, a dose-response relationship was observed for the number of elevated biomarkers at cohort entry and risk of developing PH: With each additional elevated biomarker at cohort entry, there was a 78% increase in hazard of developing PH (HR 1.78, 95% CI 1.2-2.6, p=0.004).

These data suggest that molecules involved in angiogenesis reflect vascular perturbation and elevations at first encounter can risk-stratify patients.

Mecoli, C.A., Shah, A.A., Boin, F., Wigley, F.M., and Hummers, L.K. The Utility of Plasma Vascular Biomarkers in Systemic Sclerosis: A Prospective Longitudinal Analysis. 20511. 2020 Arthritis Rheumatol.

Concepts Keywords
Angiogenesis Lesions DL scleroderma
Arthritis Medicine
Binary Variable Clinical medicine
Biomarker Organ systems
Biomarkers Autoimmune diseases
Cohort Mucinoses
Cross RTT
Digital Biomarkers
DL Medical signs
Dose Response Scleroderma
Growth Factor Systemic scleroderma
Hepatocyte Growth Factor Pulmonary hypertension
HR 2
Pulmonary Hypertension
Systemic Sclerosis


Type Source Name
disease MESH Systemic Sclerosis
disease MESH Pulmonary hypertension
disease MESH abnormalities
disease MESH development
disease MESH diagnosis

Original Article

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