Abstract 2658: Growth Differentiation Factor-15 (GDF-15) and the Risk of Recurrent Events in Patients Stabilized after Acute Coronary Syndrome: Observations from PROVE IT-TIMI 22
Growth differentiation factor 15 (GDF-15) is a transforming growth factor-β related cytokine that is induced in relation to inflammation and tissue injury. Initial studies indicate that GDF-15 at presentation with acute coronary syndromes (ACS) is associated with increased risk. We hypothesized that GDF-15 would be useful for risk assessment at hospital discharge after ACS and that the risk may be modified by statin therapy.
METHODS: We measured GDF-15 in 3,761 pts stabilized after ACS and randomized to moderate or high dose statin therapy in the PROVE IT-TIMI 22 Trial. Pts were followed for an average of 24 mo.
RESULTS: Elevated GDF-15 drawn after stabilization was strongly associated with higher rates of recurrent cardiovascular events (Fig⇓). GDF-15 > median (1362 ng/L, IQR 1032 – 1844) was associated with increased risk of death (HR 4.8; 95% CI 2.7 – 8.5), MI (HR 2.11; 95% CI 1.61 – 2.76), and CHF (HR 4.8; 95% CI 3.0 – 7.6). After adjustment for important covariates including age, gender, diabetes, smoking, hypertension, index event, renal function, CRP and BNP, GDF-15 remained independently associated with the risk of death/MI (adj HR 1.5; 95% CI 1.1 – 2.0) and death/MI/CHF (adj HR 1.7; 95% CI 1.3 – 2.2). There was no significant interaction with the randomized statin therapy (p-interaction = 0.98 and 0.90 respectively).
CONCLUSIONS: GDF-15 was independently associated with long-term risk of recurrent cardiovascular events after ACS, adding to clinical predictors, CRP and BNP. This finding in a large data set adds to the emerging evidence supporting GDF-15 as a candidate prognostic marker in pts with ACS, and supports investigation of other therapies that might modify this risk.