TY - JOUR
T1 - Prevalence of subclinical atherosclerosis is increased in systemic sclerosis and is associated with serum proteins
T2 - A cross-sectional, controlled study of carotid ultrasound
AU - Schiopu, Elena
AU - Au, Karen M.
AU - Mcmahon, Maureen A.
AU - Kaplan, Mariana J.
AU - Divekar, Anagha
AU - Singh, Ram R.
AU - Furst, Daniel E.
AU - Clements, Philip J.
AU - Ragvendra, Nagesh
AU - Zhao, Wenpu
AU - Maranian, Paul
AU - Khanna, Dinesh
N1 - Funding Information:
K.M.A. and this project were supported by the ACR Research and Education Foundation (REF) Physician Scientist Development Award. D.K. is supported by the National Institutes of Health. D.E.F. is partially supported by the National Institutes of Health. The sJAM-A assay was done with funds from Jonathan and Lisa Rye and the Marvin and Betty Danto Scleroderma Research Endowments to the University of Michigan. The type I IFN assay was done in M.J.K.’s laboratory, which is supported by the National Institutes of Health. Authors’ contributions: E.S. analysed the data and wrote the first draft of the manuscript; K.M.A. designed the protocol, carried out the project, collected the data, organized it and drafted the manuscript; M.A.M., M.J.K., W.Z. and A.D. carried out the biomarker measurements and significantly contributed to the writing of the manuscript; R.R.S. and N.R. performed the radiology portion of the study and contributed to the design and the manuscript; D.E.F. and P.J.C. reviewed the design and the manuscript; P.M. did all the statistical analysis and D.K. conceived the study and coordinated the final version of the manuscript. All authors read and approved the final manuscript.
Funding Information:
Funding statement: The study was partly funded by the National Institutes of Health/NIAMS (grants K23 AR053858 and K24 AR063120) to D.K.
PY - 2014/4
Y1 - 2014/4
N2 - Objectives: SSc is associated with an increased prevalence of atherosclerosis (ATS). This study assessed the prevalence of subclinical ATS as measured by carotid US and explored serum proteins to identify potential biomarkers of SSc-ATS.Methods: Forty-six SSc female patients and 46 age- and ethnicity-matched controls underwent carotid US to assess the presence of plaque and carotid intima media thickness (CIMT). Abstracted data included demographics, ATS risk factors and serum measurements [cholesterol, proinflammatory high-density lipoprotein (piHDL), CRP, lipoproteins]. Serum cytokines/proteins analyses included circulating type I IFN activity by quantifying IFN-inducible genes, soluble junctional adhesion molecule A (sJAM-A) and 100 serum proteins by using a microplate-based multiplex platform. Proteins significant at P < 0.05 on bivariate analyses for the presence of plaque were used to develop a composite measure.Results: Patients with SSc had more plaque (45.6% vs 19.5%, P = 0.01) but similar CIMT compared with controls. Multiplex analysis detected significant associations between serum proteins of inflammation, vasculopathy and fibrosis with ATS in SSc, including IL-2, IL-6, CRP, keratinocyte growth factor, intercellular adhesion molecule 1, endoglin, plasminogen activator inhibitor 1 and insulin-like growth factor binding protein 3 associated with carotid plaque. Myeloid progenitor inhibitory factor 1, serum amyloid A, thrombomodulin, N-terminal pro-brain natriuretic peptide (BNP), and Clara cell secretory protein 16 kD correlated with CIMT. The median composite score for the plaque group was 6 and for the no plaque group it was 2 (P < 0.0001).Conclusion: Patients with SSc have a higher prevalence of carotid plaque than matched controls, and patients with SSc-plaque vs patients without plaque have elevated serum proteins implicated in both vasculopathy and fibrosis. Further studies are needed to evaluate the role of these proteins in SSc compared with healthy controls.
AB - Objectives: SSc is associated with an increased prevalence of atherosclerosis (ATS). This study assessed the prevalence of subclinical ATS as measured by carotid US and explored serum proteins to identify potential biomarkers of SSc-ATS.Methods: Forty-six SSc female patients and 46 age- and ethnicity-matched controls underwent carotid US to assess the presence of plaque and carotid intima media thickness (CIMT). Abstracted data included demographics, ATS risk factors and serum measurements [cholesterol, proinflammatory high-density lipoprotein (piHDL), CRP, lipoproteins]. Serum cytokines/proteins analyses included circulating type I IFN activity by quantifying IFN-inducible genes, soluble junctional adhesion molecule A (sJAM-A) and 100 serum proteins by using a microplate-based multiplex platform. Proteins significant at P < 0.05 on bivariate analyses for the presence of plaque were used to develop a composite measure.Results: Patients with SSc had more plaque (45.6% vs 19.5%, P = 0.01) but similar CIMT compared with controls. Multiplex analysis detected significant associations between serum proteins of inflammation, vasculopathy and fibrosis with ATS in SSc, including IL-2, IL-6, CRP, keratinocyte growth factor, intercellular adhesion molecule 1, endoglin, plasminogen activator inhibitor 1 and insulin-like growth factor binding protein 3 associated with carotid plaque. Myeloid progenitor inhibitory factor 1, serum amyloid A, thrombomodulin, N-terminal pro-brain natriuretic peptide (BNP), and Clara cell secretory protein 16 kD correlated with CIMT. The median composite score for the plaque group was 6 and for the no plaque group it was 2 (P < 0.0001).Conclusion: Patients with SSc have a higher prevalence of carotid plaque than matched controls, and patients with SSc-plaque vs patients without plaque have elevated serum proteins implicated in both vasculopathy and fibrosis. Further studies are needed to evaluate the role of these proteins in SSc compared with healthy controls.
KW - Atherosclerosis
KW - Carotid intima media thickness
KW - Endothelial dysfunction
KW - Serum proteins
KW - Systemic sclerosis
KW - Type I interferon
UR - http://www.scopus.com/inward/record.url?scp=84897867507&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897867507&partnerID=8YFLogxK
U2 - 10.1093/rheumatology/ket411
DO - 10.1093/rheumatology/ket411
M3 - Article
C2 - 24357811
AN - SCOPUS:84897867507
SN - 1462-0324
VL - 53
SP - 704
EP - 713
JO - Rheumatology and Rehabilitation
JF - Rheumatology and Rehabilitation
IS - 4
M1 - ket411
ER -