Research Article: Serum Soluble Urokinase-Type Plasminogen Activator Receptor Is Associated with Low Left Ventricular Ejection Fraction and Elevated Plasma Brain-Type Natriuretic Peptide Level

Date Published: January 30, 2017

Publisher: Public Library of Science

Author(s): Shu-ichi Fujita, Suguru Tanaka, Daichi Maeda, Hideaki Morita, Tomohiro Fujisaka, Yoshihiro Takeda, Takahide Ito, Nobukazu Ishizaka, Vincenzo Lionetti.


Recent studies have suggested that soluble urokinase plasminogen activator receptor (suPAR), a biomarker of subclinical levels of inflammation, is significantly correlated with cardiovascular events.

We investigated the association between suPAR and left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), and plasma B-type natriuretic peptide (BNP) among cardiac inpatients.

In total, 242 patients (mean age 71.3 ± 9.8 years; 70 women) admitted to the cardiology department were enrolled in the study. suPAR was significantly correlated with LVEF (R = -0.24, P<0.001), LVMI (R = 0.16, P = 0.014) and BNP (R = 0.46, P<0.001). In logistic regression analysis, the highest suPAR tertile (> 3236 pg/mL) was associated with low LVEF (< 50%) and elevated BNP (> 300 pg/mL) with an odds ratio of 3.84 (95% confidence interval [CI], 1.22–12.1) and 5.36 (95% CI, 1.32–21.8), respectively, after adjusting for age, sex, log-transformed estimated glomerular filtration rate (log(eGFR)), C-reactive protein, and diuretic use. The association between suPAR and LVMI was not statistically significant. In multivariate receiver operating characteristic analysis, addition of log(suPAR) to the combination of age, sex, log(eGFR) and CRP incrementally improved the prediction of low LVEF (area under the curve [AUC], 0.827 to 0.852, P = 0.046) and BNP ≥ 300 pg/mL (AUC, 0.869 to 0.906; P = 0.029).

suPAR was associated with low LVEF and elevated BNP, but not with left ventricular hypertrophy, independent of CRP, renal function, and diuretic use among cardiac inpatients who were not undergoing chronic hemodialysis.

Partial Text

The receptor for urokinase-type plasminogen activator (uPAR), a membrane-linked protein, may mediate immune and inflammatory activation and cancer cell progression [1,2,3,4]. Soluble uPAR (suPAR), which is formed by the cleavage and release of uPAR, has been gathering increasing attention owing to its potential as a biomarker for the presence or progression of various diseased conditions. For example, elevated suPAR levels have been shown to be associated with chronic kidney disease (CKD) and cardiovascular abnormalities, including coronary artery disease, early cardiac systolic and diastolic myocardial impairment, heart failure, and incident cardiovascular events [5,6,7,8,9,10,11,12,13]. Recent cohort studies showed that elevated suPAR levels were independently associated with incident chronic kidney disease, a decline in the renal function [14] and hospitalization due to impaired kidney function [15].

We herein demonstrated that suPAR was associated positively with LVEF and negatively with plasma BNP levels among cardiac patients. These associations were found to be independent of eGFR, CRP, and diuretic use. On the other hand, the association between suPAR and LVH was not significant after adjusting for various confounders.




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