Growth Differentiation Factor (GDF)-15 and Cardiometabolic Outcomes among Older Adults: The Atherosclerosis Risk in Communities Study

Introduction: Laboratory studies suggest an involvement of growth differentiation factor 15 (GDF-15) in metabolic dysregulation. However, the utility of GDF-15 for assessing risk of cardiometabolic outcomes has not been rigorously examined among older adults. Methods: We conducted a cross-sectional analysis of older adults who attended visit 6 (2016-2017) of the Atherosclerosis Risk in Communities (ARIC) Study. We used multivariable logistic regression to quantify cross-sectional associations of GDF-15 (in quartiles) with prevalent diabetes, obesity, atherosclerotic cardiovascular disease (ASCVD), subclinical myocardial stress/injury (assessed by NT-proB-type Natriuretic Peptide [NT-proBNP] and high-sensitivity cardiac troponin T [hs-cTnT]), and heart failure (HF). Results: Among 3792 ARIC study participants (mean age 80 years, 59% women, 23% Blacks and 77% Whites, mean GDF-15: 2094.9 pg/mL [SD: 1395.6]), higher GDF-15 concentrations (highest vs. lowest quartile) were positively associated with diabetes (adjusted odds ratio [aOR]:]: 2.48, 95% CI: 1.89, 3.26), ASCVD (aOR: 1.57, 95% CI: 1.16, 2.11), increased hscTnT (aOR: 2.27, 95%CI: 1.54, 3.34), increased NT-proBNP (aOR: 1.98, 95%CI: 1.46, 2.70), and HF (aOR: 3.22, 95%CI: 2.13, 4.85), in models adjusted for demographics and traditional cardiovascular risk factors. Conclusions: In this sample of older US black and whites, increased GDF-15 was positively associated with diabetes, ASCVD, HF, and markers of subclinical myocardial stress or injury. These results illustrate the diverse aspects of the link between GDF-15 and diseases states, and its potential utility as robust biomarker of adverse cardiometabolic outcomes.