The Value of 4D Speckle-Tracking Strain Echocardiography in Evaluating the Relationship Between Asprosin and Growth Differentiation Factor-15 Levels and Subclinical Systolic Dysfunction in Patients With Acromegaly and Prolactinoma
Authors: Firlatan Busra , Karakulak Ugur N , Hekimsoy Vedat , Iremli Burcin G , Lay Incilay , Yuce Deniz , Dagdelen Selcuk , Kabakci Giray , Erbas Tomris A 
Published: May 2021

Abstract
Introduction: In patients with acromegaly and prolactinoma, the long-term presence of elevated GH and PRL levels is associated with an unfavorable cardiovascular risk profile. Early recognition of dysfunctions related to cardiovascular complications, which can be a significant contributor to mortality, is important. The aim of this study was to assess the relationship of four-dimensional speckle-tracking strain echocardiographic (4DSTE) measurements with asprosin, GDF-15 levels, and the Framingham cardiovascular risk score (FRS) in patients with acromegaly and prolactinoma. Methods: The study included 41 acromegaly [20F/21M, age: 49 (41-57)], 29 prolactinoma patients [18F/11M, age: 40 (28-48)] and 33 healthy control subjects [15F/18M, age: 48 (37-54)]. Data are presented as median with interquartile ranges (IQR). Anthropometric, biochemical and echocardiographic measurements were performed. Asprosin and GDF-15 levels were measured by ELISA. Results: Plasma asprosin concentration in the prolactinoma group [2.4 ng/mL (0.0-9.7)] was significantly lower than the concentration in both the acromegaly group [6.8 ng/mL (2.6-9.9)] and the control group [10.2 ng/mL (2.3-18.0)] (p=0.022 and p=0.006, respectively). In the study population, asprosin levels were positively correlated with age, FRS, and GDF-15 levels (r=0.361, p&lt;0.001; r=0.275, p=0.005 and r=0.240, p=0.015; respectively). Plasma GDF-15 concentration was lower in prolactinoma group [262.2 pg/mL (169.3-336.1)] than in the acromegaly [332.5 pg/mL (257.4-438.8)] and control groups [331.3 pg/mL (233.6-428.9)] (p=0.008 and p=0.047, respectively). In multiple linear regression analysis, GDF-15 level was independently positively related to the FRS in both patient groups (p&lt;0.001). FRS was highest in patients with acromegaly (p=0.004). In 2DE; the left ventricular ejection fraction although within normal limits, was lower in acromegaly [63% (63-65)] and prolactinoma [63% (60-65)] patients compared to the healthy controls [66% (63-68)] (p=0.003). In both acromegaly and prolactinoma groups; global longitudinal, circumferential, areal and radial strain measurements identified by 4DSTE were lower than the control group (acromegaly: p=0.007, p=0.008, p=0.015, p=0.008; prolactinoma: p=0.033, p=0.019, p=0.030, p=0.025, respectively). In contrast, diastolic functions were evaluated as normal in 85% of acromegaly patients, 86% of prolactinoma patients, and 93% of the control group (p=0.365). Conclusion: This is the first study to demonstrate the isolated subclinical systolic dysfunction identified by four-dimensional echocardiography in patients with acromegaly and prolactinoma. Asprosin may be associated with cardiovascular diseases in addition to its role in the pathogenesis of type 2 diabetes mellitus, and GDF-15 can be used as a biomarker to predict cardiovascular risk in these patient groups.