Circulating growth differentiation factor-15 levels are associated with early echocardiographic signs of diastolic function impairment in the STANISLAS cohort: A 20-year follow-up study.

Objective: Early identification of healthy subjects prone to develop cardiac dysfunction may be instrumental to prevention strategies. Our study aimed to evaluate whether circulating levels of growth differentiation factor-15 (GDF-15) could predict adverse changes in echocardiographic indexes of cardiac structure and function in an initially healthy populational familial cohort with a long follow-up (STANISLAS cohort).

Results: We evaluated 1679 participants (49 ± 14 years, 48% males) included in the fourth visit (V4) of the STANISLAS cohort with available GDF-15 measurements (Olink proteomic analysis) and echocardiographic parameters. Among them, 1562 had also GDF-15 measurements at the first visit (V1) (18.2 ± 1.4 years before V4). We evaluated both prospective (GDF-15 at V1) and cross-sectional (GDF-15 at V4) associations between GDF-15 levels and echocardiographic variables. In adjusted analyses, higher baseline GDF-15 levels were associated with lower left ventricular (LV) end-diastolic volume and higher E/e' ratio nearly two decades later (both p ≤ 0.01). The cross-sectional analysis at V4 also found significant associations between GDF-15 and LV end-diastolic volume and higher E/e' ratio, further identifying significant associations with impaired LV strain.

Conclusions: In the STANISLAS cohort, initial circulating GDF-15 levels were associated with echocardiographic signs of reduced LV size and increased filling pressure almost two decades later. This association was also confirmed by evaluating GDF-15 at the follow-up visit (V4). These findings suggest a potential role for GDF-15 as an easy screening and prognostic tool of diastolic dysfunction in the general population.