Prognostic value of growth differentiation factor-15 3 months after an acute chest pain admission

Abstract

ObjectiveGrowth differentiation factor-15 (GDF-15) is a predictor of death and cardiovascular events when measured during index hospitalisation in patients with acute chest pain. This study investigated the prognostic utility of measuring GDF-15 3 months after an admission with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS).MethodsGDF-15 was measured at baseline and 3 months after admission in 758 patients admitted with suspected NSTE-ACS. Patients were followed for a median of 1540 (IQR: 1087–1776) days after the 3-month visit. The primary endpoint was all-cause mortality, while the secondary composite endpoint included all-cause mortality, incident myocardial infarction and heart failure hospitalisation during follow-up.ResultsIn patients with GDF-15 ≥1200 pg/mL (n=248), 18% died and 25% met the composite endpoint. In patients with GDF-15 <1200 pg/mL (n=510), 1.7% died and 4% met the composite endpoint. The GDF-15 concentration (log2 transformed) at 3 months was significantly associated with all-cause mortality (adjusted HR: 2.2, 95% CI: 1.4 to 3.3, p<0.001) and the composite endpoint (adjusted HR: 1.9, 95% CI: 1.4 to 2.7, p<0.001), independently of traditional risk factors and baseline troponin T. A 10% change in GDF-15 concentration from baseline to the 3-month visit was associated with increased risk of all-cause mortality (HR: 1.06, 95% CI: 1.01 to 1.13, p=0.031), adjusting for baseline GDF-15 concentrations.ConclusionsHigh GDF-15 concentrations 3 months after admission for suspected NSTE-ACS are associated with long-term mortality and cardiovascular events, independent of traditional risk factors and troponin T. A change in GDF-15 concentration can provide prognostic information.

Evaluation of New Cardiac Damage Biomarkers in Polytrauma: GDF-15, HFABP and uPAR for Predicting Patient Outcomes

“…A cut off-value of GDF-15 was described at 1808 ng/mL in patients with a non-St-elevation acute coronary heart syndrome [32]. Interestingly, after a month of an acute chest pain, GDF-15 was also described as a prognostic marker for non-ST elevation acute coronary syndrome [33]. GDF-15 is a cytokine belonging to the transforming growth factor (TGF-) family, known to be highly up-regulated in stress and inflammatory conditions [34].…”

“…It correlates positively with several inflammatory biomarkers, including CRP, IL-6 and TNFα [41], and has been investigated as a marker of kidney-and heart-injury, as well as sepsis. suPAR or soluble urokinase plasminogen activator receptor has been described as an inflammation and immune activation -biomarker [33]. It correlates positively with several inflammatory biomarkers, including CRP, IL-6 and TNFα [34], and has been investigated as a marker of kidney-and heartinjury, as well as sepsis.…”

Psychobiological regulation of plasma and saliva GDF15 dynamics in health and mitochondrial diseases

“…Circulating GDF15 is produced by various somatic tissues and cell types, secreted and transported in the blood, eventually reaching the hindbrain (and possibly other tissues) where it signals energetic stress to alter behavior and whole-body energy expenditure [1][2][3][4][5] . GDF15 fulfills several criteria as a marker of systemic energetic stress: 1) GDF15 is the most robustly elevated circulating protein with aging 6,7 , 2) it is induced by some medications targeting mitochondria (e.g., metformin 8 ), and 3) it is elevated in several chronic physical and mental illnesses including cardiovascular disease 9 , cancer 10 , mood disorders 11 , Alzheimer's disease 12,13 autoimmune diseases 14 , and others. Moreover, 4) GDF15 is the leading candidate biomarker for primary mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations and deletions causing mitochondrial diseases (MitoD) [15][16][17][18][19][20] .…”