The Utility of Plasma Vascular Biomarkers in Systemic Sclerosis: A Prospective Longitudinal Analysis.
Adult
Biomarkers
/ blood
Endoglin
/ blood
Endostatins
/ blood
Female
Fingers
/ blood supply
Heart Disease Risk Factors
Hepatocyte Growth Factor
/ blood
Humans
Hypertension, Pulmonary
/ diagnosis
Ischemia
/ diagnosis
Longitudinal Studies
Male
Middle Aged
Neovascularization, Pathologic
/ diagnosis
Placenta Growth Factor
/ blood
Predictive Value of Tests
Proportional Hazards Models
Prospective Studies
Risk Assessment
Scleroderma, Systemic
/ blood
Vascular Endothelial Growth Factor Receptor-1
/ blood
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
18
10
2019
accepted:
17
03
2020
pubmed:
23
3
2020
medline:
15
12
2020
entrez:
23
3
2020
Statut:
ppublish
Résumé
In cross-sectional studies, pulmonary hypertension (PH) and ischemic digital lesions are 2 scleroderma vascular outcomes 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. This prospective longitudinal study was undertaken to evaluate vascular biomarker measurements in patients with systemic sclerosis (SSc) over time. We conducted a prospective cohort study of 300 patients with SSc who were followed up for at least a 5-year period and lacked evidence of PH and/or active ischemic digital lesions at enrollment. Levels of hepatocyte growth factor (HGF), soluble Flt-1 (sFlt-1), soluble endoglin, endostatin, and placental growth factor (PLGF) were obtained at multiple time points and assessed for their ability to predict the development of PH/ischemic digital lesions. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated. Forty-six patients (15%) developed PH and 69 patients (23%) developed an ischemic digital lesion. In time-to-event analyses, the following 3 biomarkers measured at cohort entry were found to be significantly associated with the development of PH: HGF (HR 1.99 [95% CI 1.24-3.17], P = 0.004), sFlt-1 (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 the risk of developing PH. With each additional elevated biomarker at cohort entry, there was a 78% increase in the risk 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 that elevations in these biomarkers at first encounter can indicate patients who are at risk of PH development.
Identifiants
pubmed: 32200572
doi: 10.1002/art.41265
pmc: PMC8214152
mid: NIHMS1710765
doi:
Substances chimiques
Biomarkers
0
ENG protein, human
0
Endoglin
0
Endostatins
0
HGF protein, human
0
PGF protein, human
0
Placenta Growth Factor
144589-93-5
Hepatocyte Growth Factor
67256-21-7
FLT1 protein, human
EC 2.7.10.1
Vascular Endothelial Growth Factor Receptor-1
EC 2.7.10.1
Types de publication
Evaluation Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1341-1349Subventions
Organisme : NHLBI NIH HHS
ID : P50 HL084946
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR073208
Pays : United States
Organisme : NIAMS NIH HHS
ID : 1K23AR075898-01A1
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30-AR-070254
Pays : United States
Organisme : NIAMS NIH HHS
ID : K23 AR052742
Pays : United States
Organisme : NIAMS NIH HHS
ID : K23 AR075898
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32AR048522
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR-073208
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR070254
Pays : United States
Organisme : NHLBI NIH HHS
ID : P50-HL084946-01
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR048522
Pays : United States
Organisme : NIAMS NIH HHS
ID : 5K23AR52742-5
Pays : United States
Informations de copyright
© 2020, American College of Rheumatology.
Références
Stat Med. 2012 Oct 15;31(23):2676-86
pubmed: 22307964
Arthritis Rheum. 2011 Aug;63(8):2456-64
pubmed: 21538327
Arthritis Rheum. 2013 Sep;65(9):2412-23
pubmed: 23740572
J Dermatol Sci. 2010 Jun;58(3):229-31
pubmed: 20451352
Clin Rheumatol. 2018 Sep;37(9):2429-2437
pubmed: 29804150
Arthritis Rheum. 2011 Sep;63(9):2790-6
pubmed: 21547892
Arthritis Res Ther. 2015 Aug 06;17:201
pubmed: 26245195
N Engl J Med. 2016 Jan 7;374(1):13-22
pubmed: 26735990
JAMA Cardiol. 2017 Dec 1;2(12):1361-1368
pubmed: 29071338
Ann Rheum Dis. 2007 Jun;66(6):754-63
pubmed: 17234652
Circulation. 1999 Nov 9;100(19 Suppl):II301-8
pubmed: 10567320
J Rheumatol. 2009 Mar;36(3):576-82
pubmed: 19228661
Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii19-24
pubmed: 19487218
Arthritis Rheum. 2008 Jan;58(1):284-91
pubmed: 18163505
Arthritis Rheumatol. 2014 Jul;66(7):1900-8
pubmed: 24729406
Ann Rheum Dis. 2013 Jul;72(7):1136-40
pubmed: 22887850
J Rheumatol. 2007 Dec;34(12):2423-30
pubmed: 17985402
Semin Arthritis Rheum. 2016 Oct;46(2):200-208
pubmed: 27312381
Arthritis Rheum. 2003 Dec;48(12):3503-8
pubmed: 14674001
Ann Rheum Dis. 2003 Nov;62(11):1088-93
pubmed: 14583573
Microcirculation. 2014 Jul;21(5):368-79
pubmed: 24410720
Am J Respir Crit Care Med. 2009 Nov 1;180(9):881-6
pubmed: 19679693
Oncol Lett. 2018 Jul;16(1):687-702
pubmed: 29963134
Eur Respir J. 2019 Jan 24;53(1):
pubmed: 30545968
Hepatology. 2018 Aug;68(2):634-651
pubmed: 29023811
Ann Rheum Dis. 2012 Mar;71(3):394-9
pubmed: 22085793
Arthritis Rheumatol. 2018 Feb;70(2):162-170
pubmed: 29145709
Autoimmun Rev. 2015 Apr;14(4):314-22
pubmed: 25485941
Circulation. 2016 Mar 29;133(13):1240-8
pubmed: 26873944
Eur J Haematol. 2018 Jun;100(6):630-635
pubmed: 29543340
Arthritis Care Res (Hoboken). 2011 Jan;63(1):142-9
pubmed: 20740608
Ann Rheum Dis. 2008 Jan;67(1):120-3
pubmed: 17660220
Ann Rheum Dis. 2007 Jul;66(7):940-4
pubmed: 17329309
J Rheumatol. 2011 Oct;38(10):2186-92
pubmed: 21885489
JCI Insight. 2017 Feb 9;2(3):e90905
pubmed: 28194443
Clin Exp Rheumatol. 2017 Sep-Oct;35 Suppl 106(4):106-113
pubmed: 27908301