Growth-Differentiation Factor-15 Is a Robust, Independent Predictor of 11-Year Mortality Risk in Community-Dwelling Older Adults: The Rancho Bernardo Study

Study Questions:

Are elevated plasma levels of growth-differentiation factor-15 (GDF-15) predictive of mortality in subjects without a known history of cardiovascular disease (CVD)?

Methods:

Plasma levels of GDF-15, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) were measured in 1,391 Rancho Bernardo Study participants, mean age 70 years, with no history of CVD. Follow-up was 11 years.

Results:

GDF-15 was an independent predictor of all-cause, CV, and non-CV mortality, and was a stronger predictor of all-cause mortality than either NT-proBNP or CRP (hazard ratio [HR] per standard deviation log10 units, 1.5; p < 0.0001 for GDF-15 versus 1.3, p < 0.0001 for NT-proBNP; CRP was not a significant predictor). Only GDF-15 predicted non-CV death (HR, 1.6; p < 0.0001). GDF-15 improved discrimination and reclassification for all-cause and non-CV mortality with borderline improvement for CV mortality; NT-proBNP significantly improved reclassification for all-cause and for CV mortality; CRP did not improve reclassification for any endpoint tested. Participants in the highest quartile of both GDF-15 and NT-proBNP had an increased risk of death compared with participants with only NT-proBNP elevated (HR, 1.5; p = 0.01).

Conclusions:

The authors concluded that GDF-15 is a strong predictor of all-cause, CV, and non-CV mortality in community-dwelling older individuals.

Perspective:

GDF-15 is a member of the transforming growth factor-β cytokine superfamily that is up-regulated in the setting of myocardial and vascular diseases. Elevated plasma levels of GDF-15 have been shown to provide added prognostic information in the setting of acute coronary syndrome and congestive heart failure. The current study expands the potential usefulness of this informative biomarker by demonstrating its independent predictive value for mortality in subjects with no previous history of CVD. Further studies are necessary to confirm these findings in other cohorts, as well as to test possible therapeutic and lifestyle interventions in patients with elevated GDF-15 levels.

Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, ACS and Cardiac Biomarkers, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Acute Coronary Syndrome, Follow-Up Studies, Biological Markers, Transforming Growth Factors, Growth Differentiation Factor 15, Heart Failure, Natriuretic Peptide, Brain


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