Soluble Urokinase Plasminogen Activator Receptor Is Associated With Subclinical Myocardial Impairment by Speckle Tracking Echocardiography in Lung Cancer Patients

Abstract

Background: Plasma cardiac biomarkers have emerged as a cost-effective diagnostic tool aimed at early identification of cardiotoxicity. Soluble urokinase plasminogen activator receptor (suPAR) is a bone marrow cell derived signaling molecule that is associated with cardiovascular disease outcomes.

Objectives: We investigated associations between suPAR and global longitudinal strain (GLS) as a marker of early myocardial impairment in lung cancer patients.

Methods: We retrospectively analyzed 52 patients with stage IV non-small cell lung cancer with normal left ventricular ejection fraction (LVEF >55%) and without known heart disease or end-stage renal disease (ESRD). We studied associations between cardiac biomarkers and echocardiographic measures of systolic and diastolic function. GLS was analyzed using 2D speckle-tracking echocardiography via vendor-independent software (TomTec).

Results: Median plasma suPAR was 7.0 ng/mL (interquartile range: 5.4-9.0). Mean LVEF was 61.9 ± 8.3% and mean GLS was-19.3 ± 2.1%. Inter-observer reproducibility was excellent for GLS as determined by Intraclass Correlation Coefficient analysis, ICC = 0.81 (0.68-0.89). After multivariate analysis, suPAR was the only biomarker associated with GLS (p = 0.009). suPAR was also associated with diastolic parameters E velocity (p = 0.018), A velocity (p = 0.017), and E/E' ratio (p = 0.033). Interestingly, suPAR was not associated with LVEF (p = 0.916). In addition, suPAR and GLS were found to be age-independent predictors of all-cause mortality, though only GLS remained significant after multivariate adjustment.

Conclusions: In this cohort of stage IV non-small cell lung cancer patients with normal LVEF and without known heart disease or ESRD, suPAR was associated with GLS and diastolic impairment. suPAR is a readily available inexpensive biomarker; further research is required to evaluate the possible role of suPAR in screening for subclinical LV dysfunction in the high-risk oncological population.

Keywords: biomarkers; cancer; myocardial global longitudinal strain; soluble urokinase plasminogen activator receptor (suPAR); speckle tracking echocardiography.

Figure 1

Study population flowchart. Displays the initial study population through the final study population, exclusions included. ESRD, End Stage Renal Disease; LVEF, Left Ventricular Ejection Fraction; NSCLC, Non-Small Cell Lung Cancer; suPAR, soluble urokinase-type Plasminogen Activator Receptor.

Figure 2

Two-dimensional speckle tracking echocardiography analysis. Strain curves and a color-coded 16-segment bull's eye plot are presented. Color lines indicate regional strain. Values of longitudinal strain are negative (sign –). Endocardial border tracing in apical four-chamber view can be achieved automatically. Global longitudinal strain (GLS) can be calculated from standard apical 4-, 2-, and 3- chamber views.

Figure 3

Correlation Analysis between the serum concentration of suPAR and echocardiographic parameters. The correlation analysis graphs demonstrate significant correlations between suPAR levels and GLS, E velocity, A velocity, and E/E'. suPAR levels were not associated with LVEF. GLS, Global Longitudinal Strain; LVEF, Left Ventricular Ejection Fraction; r, Pearson's correlation coefficient; suPAR, soluble urokinase-type Plasminogen Activator Receptor.