Background:
Growth differentiation factor (GDF)-15, a stress responsive cytokine, is associated with the risk of CV events after an acute coronary syndrome (ACS). Unlike other established cardiac biomarkers, the level of GDF-15 remains elevated in sub-acute phase after ACS and gradually decreases over time. We evaluated the prognostic utility of GDF-15 in patients after ACS accounting for established markers and risk predictors.
Methods:
GDF-15 (R&D Systems) and other established cardiac biomarkers (BNP, hsCRP and hsTnI) were measured at baseline in a randomly selected cohort of 4,968 patients enrolled within 30 days of hospitalization with ACS (median=14d) in SOLID-TIMI 52. Previously defined cutpoints were applied for GDF-15 concentration: <1200 (n=3451), 1200-1800 (n=919), and > 1800 ng/L (n=598). Analyses were adjusted for established risk predictors, days from the ACS event and other markers. MACE was defined as CV death, MI or stroke. Median follow-up was 2.5 years.
Results:
Patients with higher GDF-15 tended to be older, more likely to have diabetes, hypertension, history of revascularization, and CKD at baseline. Higher baseline levels of GDF-15 identified patients with higher rates of MACE as well as each individual element (p-trend <0.001 for all endpoints, Fig). The rate of MI was ∼2-fold higher in those with GDF-15 concentration >1800ng/L compared to patients with GDF-15 concentration <1200 ng/L. After adjustment for clinical predictors and other markers, GDF-15 was independently associated with the risk of MACE (HR 1.4, 95% CI 1.1-1.7; HR 1.8, 95% CI 1.4-2.3 for GDF-15 1200-1800, >1800, respectively). Individuals with GDF-15 >1800 ng/L had an increased risk of MI (adj HR 1.4, 95% CI 1.1-2.0) and stroke (adj HR 2.3, 95% CI 1.3-3.9).
Conclusion:
In patients after ACS, GDF-15 concentration is associated with the risk of MACE including MI and stroke independent of traditional risk factors and risk markers.
Clinical Predictors of Culprit Plaque Rupture Assessed on Intravascular Ultrasound in Acute Coronary Syndrome
