Abstract 12810: Elevated Circulating Levels of Growth-Differentiation Factor-15 in Elderly Subjects with Preclinical Left Ventricular Alterations

Abstract

Purpose: Growth-differentiation factor-15 (GDF-15), a member of the transforming growth factor-β cytokine superfamily, emerges as a prognostic marker in patients with established CV disease. We tested the hypothesis that GDF-15 allows early detection of preclinical LV alterations in unselected elderly people of the general population.

Methods: We measured plasma GDF-15 levels (ECLIA, Roche Diagnostics) and performed detailed echocardiographic exams in 2001 elderly subjects (mean age 73±5 years, 48% women), resident in central Italy (PREDICTOR study). LV systolic function was measured at either the endocardial (LVEF) or midwall level (midwall fractional shortening, MFS).

Results: In this large cohort, 87% of the subjects had normal hs-cTnT levels (<14 ng/L) and 92% normal NT-proBNP. Subjects with high GDF-15 (median 1468 [1168-1984] ng/L) were on average older, more often males, had reduced renal function and more prevalent CV risk factors (hypertension, diabetes, smoking, BMI). MFS significantly decreased across increasing quartiles of GDF-15 (from 14.3% in Q1 to 11.8% in Q4, p=0.0001) while LVEF was not statistically associated (from 66.9% to 64.5%, p=0.12). Among individuals with normal LV mass, GDF-15 was higher in those with subnormal MFS (<15%, 1506 [1219-1989] ng/L, n=275) than in those with normal MFS (≥15%, 1392 [1117-1801] ng/L, n=918, p=0.03) while there was no statistical differences for NT-proBNP (80 [42-170] vs. 78 [40-148] ng/L, p=0.35). The same was true among subjects for elevated LV mass (p=0.005 and 0.55, for GDF-15 and NT-proBNP). GDF-15 was associated with elevated LV mass, even after adjustment for cardiac markers or clinical risk factors.

Conclusions: GDF-15 can provide information independent of traditional cardiac biomarkers or CV risk factors to identify elderly subjects with subnormal midwall fractional shortening, a pre-clinical stage during the progression to LV hypertrophy and HF.