Growth differentiation factor 15 and cardiovascular events in patients with stable ischemic heart disease (The Heart and Soul Study).
BACKGROUND
Growth differentiation factor 15 (GDF-15) is a relatively new biomarker that predicts mortality in patients with chronic stable angina or acute coronary syndrome. However, the association of GDF-15 with cardiovascular (CV) events and the mechanisms of this association are not well understood.


METHODS
We measured plasma GDF-15 and cardiac disease severity in 984 patients with stable ischemic heart disease who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent CV events (myocardial infarction, stroke, and CV death), hospitalization for heart failure, and all-cause mortality were determined by chart review during an average of 8.9-year follow-up.


RESULTS
Each doubling in GDF-15 was associated with a 2.5-fold increased rate of CV events (hazard ratio [HR] 2.53, 95% CI 2.13-3.01, P < .001). This association persisted after extensive adjustment for covariates including comorbid conditions, measures of cardiac disease severity, cardiac function, inflammatory markers, and adipokines (HR 1.44, 95% CI 1.11-1.87, P < .01). Participants who had GDF-15 levels in the highest tertile had higher mortality compared with those in the lowest tertile (HR 2.73, 95% CI 1.80-4.15, P ≤ .001 adjusted for all covariates). Addition of GDF-15 to existing risk factors resulted in a 50% change in net reclassification of patients' risk for mortality.


CONCLUSIONS
Higher levels of GDF-15 are associated with major CV events in patients with stable ischemic heart disease. This suggests that GDF-15 is capturing an element of risk not explained by other known risk factors.
San Francisco VA Medical Center, San Francisco, CA. Electronic address: david.schopfer@ucsf.edu.
David W
DW
Schopfer
Department of Cardiology, Kaiser Permanente San Francisco, San Francisco, CA.
Ivy A
IA
Ku
San Francisco VA Medical Center, San Francisco, CA.
Mathilda
M
Regan
San Francisco VA Medical Center, San Francisco, CA; Department of Medicine, University of California, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.
Mary A
MA
Whooley
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002140:California / Q000453:epidemiology; D002423:Cause of Death / Q000639:trends; D005260:Female; D005500:Follow-Up Studies; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006333:Heart Failure / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D017202:Myocardial Ischemia / Q000097:blood* / Q000150:complications / Q000401:mortality; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D015996:Survival Rate / Q000639:trends
D015415:Biomarkers; D055436:Growth Differentiation Factor 15