Associations between Growth Differentiation Factor 15, Cardiac Troponin T, and N-terminal pro-B-type Natriuretic Peptide, and Future Myocardial Fibrosis Assessed by Cardiac Magnetic Resonance Imaging: Data from the Akershus Cardiac Examination 1950 Study

Abstract Background Myocardial fibrosis is associated with a poor outcome for patients with cardiovascular disease (CVD). Growth differentiation factor 15 (GDF-15) concentrations predict the risk of death in patients with CVD, but the underlying pathophysiological mechanisms are poorly understood. We aimed to assess the associations between biomarkers of cellular stress and inflammation (GDF-15), cardiac injury (cardiac troponin T [cTnT]), and stretch (N-terminal pro-B-type natriuretic peptide [NT-proBNP]), and subsequent focal and diffuse myocardial fibrosis assessed by cardiac magnetic resonance (CMR) imaging. Methods We measured GDF-15, cTnT, and NT-proBNP in 200 study participants without known coronary artery disease or renal dysfunction from the population-based Akershus Cardiac Examination 1950 Study at baseline in 2012 to 2015. Focal myocardial scars and diffuse fibrosis were assessed by late gadolinium enhancement imaging and septal extracellular volume fraction (ECV) by CMR 4 to 7 years later. The relationships between cardiac biomarkers and CMR parameters were assessed by logistic regression analysis adjusted for common cardiovascular risk factors. Results The median age was 63.9 (interquartile range 63.4–64.5) years and 49% were women. GDF-15 (adjusted odds ratio [aOR] 4.40, 95% CI 1.09–17.72) and cTnT (aOR 1.59, 95% CI 1.01–2.50) were associated with nonischemic scars in the fully adjusted model. cTnT (aOR 2.45, 95% CI 1.41–4.25) and NT-proBNP (aOR 3.12, 95% CI 1.55–6.28) were associated with ischemic scars. None of the biomarkers were significantly associated with elevated ECV. Conclusions In a general population cohort, GDF-15, an emerging biomarker of cellular stress and inflammation, associates with nonischemic scars. Biomarkers of myocardial injury and stretch associate with ischemic scars, while no biomarker was associated with diffuse fibrosis as assessed by CMR.