GDF-15 predicts death far better than it diagnoses obstructive coronary disease

Design

Prospective cohort with central adjudication and 5-year follow-up

Population

3,379 patients with suspected functionally relevant coronary artery disease; median age 68

Primary outcome

Diagnosis of functionally relevant coronary disease; all-cause and cardiovascular death

Effect

Diagnostic AUC 0.598 (0.659 with clinical judgement); 2-year prognostic AUC 0.815 (all-cause) and 0.834 (cardiovascular death)

In this prospective cohort, 3,379 patients (median age 68, 33% women, 44% with known coronary disease) had myocardial perfusion imaging and, when available, angiography with fractional flow reserve. Functionally relevant coronary disease was centrally adjudicated in 1,160 (34%).

Growth differentiation factor 15 was higher in those with the diagnosis (1,325 vs 1,041 ng/L), but diagnostic accuracy was modest, with an area under the curve of 0.598, rising to 0.659 when combined with clinical judgement. Prognostically it performed far better. Over 5 years, 437 patients (14%) died, 231 from cardiovascular causes, and time-dependent AUCs at 2 years were 0.815 for all-cause and 0.834 for cardiovascular death, at least comparable to high-sensitivity troponin T and higher than troponin I.

GDF-15 is not a routine test in most hospitals, and the study does not show that acting on a high value improves outcomes. It is an indication that the marker tracks overall frailty and risk better than it locates a coronary lesion.

• Do not use GDF-15 to decide whether chest pain is due to obstructive coronary disease.
• Treat a high level, if measured, as a general risk signal and review risk factors and frailty.
• Continue to use functional testing or imaging for the diagnosis.
• Check local availability before planning to use it; it is not a standard test.

Why it matters

It separates two jobs a biomarker can do, diagnosis and prognosis, and shows this one does only the second.

Don't overread it

Good prognostic accuracy does not mean that measuring or lowering GDF-15 improves survival.

The statistics, in plain English

An area under the curve of 0.5 is a coin toss and 1.0 is perfect. At 0.598, GDF-15 barely discriminates for the diagnosis; at about 0.82 to 0.83 it discriminates well for death at 2 years.

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