Growth differentiation factor-15 and risk of recurrent events in patients stabilized after acute coronary syndrome: observations from PROVE IT-TIMI 22.
OBJECTIVE
To investigate growth differentiation factor (GDF)-15 at hospital discharge for assessment of the risk of death, recurrent myocardial infarction (MI), and congestive heart failure, and to determination of whether these risks can be modified by statins.


RESULTS
GDF-15 is a transforming growth factor-β-related cytokine induced in response to tissue injury. GDF-15 concentration is associated with all-cause mortality in patients with acute coronary syndrome (ACS). We measured GDF-15 in 3501 patients after ACS, treated with moderate or intensive statin therapy in PROVE IT-TIMI 22. By using established cutoff points, GDF-15 (<1200, 1200-1800, and >1800 ng/L) was associated with 2-year risk of death or MI (5.7%, 8.1%, and 15.1%, respectively; P<0.001), death (P<0.001), MI (P<0.001), and congestive heart failure (P<0.001). After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, smoking, MI, qualifying event, renal function, B-type natriuretic peptide, and high-sensitivity C-reactive protein, GDF-15 was associated with the risk of death or MI (adjusted hazard ratio per ln increase GDF-15, 2.1 [95% CI, 1.6 to 2.9]; P<0.001), death (P<0.001), MI (P<0.001), and congestive heart failure (P<0.001). There was no significant interaction between GDF-15 and intensive statin therapy for the risk of death or MI (P=0.24 for the interaction).


CONCLUSIONS
GDF-15 is associated with recurrent events after ACS, independent of clinical predictors, B-type natriuretic peptide, and high-sensitivity C-reactive protein. This finding supports GDF-15 as a prognostic marker in ACS and investigation of other therapies that modify this risk.
TIMI Study Group, Brigham and Women's Hospital, Boston, MA 02115, USA. mbonaca@partners.org
Marc P
MP
Bonaca
David A
DA
Morrow
Eugene
E
Braunwald
Christopher P
CP
Cannon
Songtao
S
Jiang
Stephanie
S
Breher
Marc S
MS
Sabatine
Tibor
T
Kempf
Lars
L
Wallentin
Kai C
KC
Wollert
D054058:Acute Coronary Syndrome / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy*; D000368:Aged; D000789:Angina, Unstable / Q000097:blood / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016009:Chi-Square Distribution; D005060:Europe; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006333:Heart Failure / Q000097:blood / Q000209:etiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010351:Patient Discharge; D016016:Proportional Hazards Models; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000209:etiology; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein