Growth differentiation factor 15 – a strong prognostic marker in patients presenting with acute chest pain without acute myocardial infarction
Authors: Myrmel G M S , Steiro O T , Tjora H L , Langoergen J , Bjoerneklett R , Skadberg Ø , Bonarjee V V S , Mjelva Ø.R , Vikenes K , Omland T , Aakre K M 
Published: October 2021

Abstract

Background
Patients who present with acute chest pain who are not diagnosed with acute myocardial infarction (AMI) may still carry an increased cardiovascular risk. Growth differentiation factor-15 (GDF-15) has earlier been shown to be a strong prognostic marker in the general population and after AMI. However, the prognostic value in the chest pain population without AMI is unknown.

Purpose
The objective of this study was to investigate the prognostic power of GDF-15 in patients presenting with acute chest pain without myocardial infarction.

Methods
A total of 984 patients admitted with suspected NSTE-ACS were included. After excluding patients with AMI the remaining 849 patients were followed for median 722 days (range 1 to 1112 days). The primary endpoint was all-cause mortality. The secondary endpoint was all-cause mortality or AMI. GDF-15 was measured in biobanked admission samples, and patients were divided into two groups based on GDF-15 levels (1: ≤1800 pg/ml, 2: &gt;1800 pg/ml). Kaplan-Meier survival curves according to GDF-15 concentrations ≤1800 pg/ml or &gt;1800 pg/ml were generated. Cox proportional hazards regression analysis was used to estimate unadjusted and adjusted hazard ratios, the latter using age, sex, hypercholesterolemia, current smoking, diabetes, hypertension, BMI, previous myocardial infarction and eGFR &lt;60ml/min/1.73m2 as covariates. The incremental prognostic value of adding GDF-15 to cardiac troponin T was estimated.

Results
GDF-15 concentrations were strongly associated with outcome. GDF-15 concentration were higher in non-survivors than survivors (median 2572 pg/ml vs. 910 pg/ml, p&lt;0,001). In the category with GDF-15 &gt;1800 pg/ml, 28 (17.9%) died, and 49 (31.4%) patients met the secondary endpoint, whereas in the category with GDF-15 levels &lt;1800 pg/ml, only 12/693 (1.7%) died and 25 (3.6%) reached the secondary endpoint, respectively. GDF-15 &gt;1800 pg/ml was associated with an increased risk of death with an unadjusted hazard ratio (HR) of 10.9 (95% CI: 5.6 – 21.5, p: 0.001) and an adjusted HR of 5.2 (95% CI: 1.4 – 19.4, p: 0.014). The risk of death or AMI in patients with GDF-15 &gt;1800 pg/ml was also increased with an unadjusted HR of 9.5 (95% CI 5.9 – 17.7 p: 0.001) and an adjusted hazard ratio of 4.6 (95% CI: 1.7–12.27, p: 0.002). Adding GDF-15 to troponin T led to an increase in C-statistic from: 0.80 (95% CI: 0.73- 0.88) to 0.86 (95% CI 0.79 – 0.91) in predicting all-cause mortality. The optimal cut-off value for predicting the primary endpoint was estimated to be 1818 pg/ml, resulting in a Youden Index of 0.55 with a specificity of 85% and sensitivity of 70%.

Conclusion
GDF-15 is a strong prognostic marker in patients presenting with acute chest pain without AMI and may aid identifying those patients with high cardiovascular risk who require further diagnostics and treatment.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Western Norway Regional Health Authority