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Published on: June 14, 2016
Associations between Growth Differentiation Factor 15, Cardiac Troponin T, and N-terminal pro-B-type Natriuretic
Thakshani Wimalanathan1,2, Michael Fredrik Paus2,3, Julia Brox Skranes2
1Department of Diagnostic Imaging, Division of Diagnostics and Technology, Akershus University Hospital, Lørenskog, Norway.
Insights
Growth differentiation factor 15 (GDF-15) and cardiac troponin T (cTnT) are linked to nonischemic scars. Biomarkers for myocardial injury and stretch correlate with ischemic scars, but not diffuse fibrosis.
Area of Science:
- Cardiology
- Biomarkers
- Medical Imaging
Background:
- Myocardial fibrosis is a negative prognostic indicator in cardiovascular disease (CVD).
- Growth differentiation factor 15 (GDF-15) predicts mortality in CVD patients, but its role in fibrosis is unclear.
- Understanding mechanisms linking biomarkers to fibrosis is crucial for CVD management.
Purpose of the Study:
- To investigate associations between biomarkers of cellular stress (GDF-15), cardiac injury (cTnT), and stretch (NT-proBNP) and myocardial fibrosis.
- To differentiate between focal (scar) and diffuse fibrosis using cardiac magnetic resonance (CMR) imaging.
- To explore the predictive value of these biomarkers for different types of myocardial fibrosis.
Main Methods:
- GDF-15, cTnT, and NT-proBNP levels were measured in 200 participants from the Akershus Cardiac Examination 1950 Study.
- Focal myocardial scars and diffuse fibrosis were assessed using CMR imaging (late gadolinium enhancement and ECV fraction) 4-7 years post-baseline.
- Logistic regression analysis, adjusted for cardiovascular risk factors, was used to determine relationships between biomarkers and fibrosis.
Main Results:
- GDF-15 and cTnT were associated with nonischemic scars.
- cTnT and NT-proBNP were associated with ischemic scars.
- No significant association was found between any biomarker and elevated extracellular volume (diffuse fibrosis).
Conclusions:
- GDF-15 is associated with nonischemic myocardial scarring in a general population.
- Biomarkers of cardiac injury and stretch are linked to ischemic scars.
- Current biomarkers do not predict diffuse myocardial fibrosis as assessed by CMR.
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.
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