Circulating soluble urokinase plasminogen activator receptor levels and peripheral arterial disease outcomes

• Type of Material: Article
• Authors: Ayman Samman Tahhan, Emory University; Salim S. Hayek, Emory University; Pratik Sandesara, Emory University; Jamal Hajjari, Emory University; Muhammad Hammadah, Emory University; Wesley T. O'Neal, Emory University; Heval M. Kelli, Emory University; Ayman Alkhoder, Emory University; Nima Ghasemzadeh, Emory University; Yi-An Ko, Emory University; Hiroshi Aida, Emory University; Mohamad Mazen Gafeer, Emory University; Naser Abdelhadi, Emory University; Kareem Hosny Mohammed, Emory University; Keyur Patel, Emory University; Shipra Arya, Emory University; Jochen Reiser, Rush University; Viola Vaccarino, Emory University; Laurence S Sperling, Emory University; Arshed Ali Quyyumi, Emory University
• Language: English
• Date: 2017-09-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.atherosclerosis.2017.06.019
• Title of Journal or Parent Work: Atherosclerosis
• ISSN: 0021-9150
• Volume: 264
• Start Page: 108
• End Page: 114
• Grant/Funding Information: AAQ is supported by 5P01HL101398-02, 1P20HL113451-01, 1R56HL126558-01, 1RF1AG051633-01, R01 NS064162-01, R01 HL89650-01, HL095479-01, 1U10HL110302-01, 1DP3DK094346-01, 2P01HL086773-06A1.; PS is supported by the Abraham J. & Phyllis Katz Foundation (Atlanta, GA).; AT is supported by the Abraham J. & Phyllis Katz Foundation (Atlanta, GA) and NIH/NIA grant AG051633.
• Keywords: CAD; PAD-Related outcomes; UPAR; INFLAMMATION; CELLS; BIOMARKERS; Cardiac & Cardiovascular Systems; PATHOGENESIS; Life Sciences & Biomedicine; SuPAR; C-REACTIVE-PROTEIN; Atherosclerosis; RISK; Cardiovascular System & Cardiology; Peripheral Vascular Disease; ATHEROSCLEROSIS; EPIDEMIOLOGY; Cardiovascular outcomes; PAD; Science & Technology; EXPRESSION
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Epidemiology; Biology, Biostatistics

Abstract

Background and aims Circulating soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation associated with atherosclerosis. Whether suPAR levels are associated with prevalent peripheral arterial disease (PAD) and its adverse outcomes remains unknown and is the aim of the study. Methods SuPAR levels were measured in 5810 patients (mean age 63 years, 63% male, 77% with obstructive coronary artery disease [CAD]) undergoing cardiac catheterization. The presence of PAD (n = 967, 17%) was classified as carotid (36%), lower/upper extremities (30%), aortic (15%) and multisite disease (19%). Multivariable logistic and Cox regression models were used to determine independent predictors of prevalent PAD and outcomes including all-cause death, cardiovascular death and PAD-related events after adjustment for age, gender, race, body mass index, smoking, diabetes, hypertension, hyperlipidemia, renal function, heart failure history, and obstructive CAD. Results Plasma suPAR levels were 22.5% (p < 0.001) higher in patients with PAD compared to those without PAD. Plasma suPAR was higher in patients with more extensive PAD (≥2 compared to single site) p < 0.001. After multivariable adjustment, suPAR was associated with prevalent PAD; odds ratio (OR) for highest compared to lowest tertile of 2.0, 95% CI (1.6–2.5) p < 0.001. In Cox survival analyses adjusted for clinical characteristics and medication regimen, suPAR (in the highest vs. lowest tertile) remained an independent predictor of all-cause death [HR 3.1, 95% CI (1.9–5.3)], cardiovascular death [HR 3.5, 95% CI (1.8–7.0)] and PAD-related events [HR = 1.8, 95% CI (1.3–2.6) p < 0.001 for all]. Conclusions Plasma suPAR level is predictive of prevalent PAD and of incident cardiovascular and PAD-related events. Whether SuPAR measurement can help screen, risk stratify, or monitor therapeutic responses in PAD requires further investigation.