Growth differentiation factor-15 may help predict mortality in older adults

The biomarker growth differentiation factor-15 (GDF-15) may help predict mortality in older community-dwelling adults, a new study indicates.

GDF-15, previously known as macrophage-inhibitory cytokine-1, is part of the superfamily of growth factor-β cytokines. It is usually expressed by activated macrophages in low levels but is upregulated in massive myocardial infarction and is expressed by atherosclerotic plaques and overexpressed in several types of malignancies. The authors noted that in previous studies, GDF-15 has added prognostic information to more standard cardiovascular biomarkers and risk factors in patients who had acute coronary syndromes and chronic heart failure.

In the current study, the researchers measured levels of plasma GDF-15, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein in stored samples of blood from 1,391 patients who participated in the Rancho Bernardo Study, a population-based epidemiologic study performed in Southern California between 1972 and 1974. Patients included in the study had no history of cardiovascular disease (CVD) at a follow-up visit that took place between 1992 and 1996. The objective of the current study was to determine whether GDF-15 independently predicted increased risk for death in this population. The primary outcome was all-cause mortality, and the secondary outcomes were fatal CVD and noncardiovascular death. The study was published online May 2 by Circulation.

Baseline for the current study was defined as the visit that took place between 1992 and 1996. Patients were followed for a mean of 11 years. The mean age of the study population at baseline was 70 years, and 36% of patients were men. The median level of GDF-15 was 1,268 ng/mL, with higher levels in men than in women (1,349 ng/L vs. 1,229 ng/L; P=0.001). After adjustment for traditional CVD risk factors, GDF-15 predicted all-cause, cardiovascular and noncardiovascular death and was a better predictor of all-cause mortality than NT-proBNP or C-reactive protein, the latter of which was not a significant predictor. GDF-15 was the only biomarker studied that predicted noncardiovascular death (hazard ratio, 1.6; P<0.0001). Elevated levels of both GDF-15 and NT-proBNP conferred a greater risk for death than did elevated NT-proBNP levels alone (hazard ratio, 1.5; P=0.01).

The authors acknowledged that most of the study participants were white and of similar socioeconomic status, limiting generalizability. They also pointed out that existing CVD could have been misclassified and that blood samples were stored for over a decade before GDF-15 levels were measured. However, they concluded that GDF-15 appears to be a strong predictor of all-cause, cardiovascular and noncardiovascular death in community-dwelling older adults without known CVD.

“This emerging biomarker may be a useful addition to current tools for risk stratification if results are confirmed in other cohorts,” the authors wrote.