D-dimer, hsCRP, Ghrelin, MMP3 and Eotaxin Correlate with Ejection Fraction in Cardiomyopathy

Introduction There is growing interest in identifying new biomarkers in cardiomyopathy. Most recently, clinical trials with treatment strategies targeting tumor necrosis factor α in CHF patients yielded disappointing results, suggesting the pathophysiology is even more complicated than originally thought. To investigate further, we assessed 58 soluble mediators known to be associated with cardiovascular disease for their relationship with cardiomyopathy. Methods Consecutive asymptomatic patients with carotid atherosclerosis followed in the Oklahoma City Veterans Affairs Vascular Medicine clinic between 2015-2017, with a TTE within three years of enrollment were eligible. Plasma was obtained at baseline for measurement of soluble mediators using 50-plex (Thermo Scientific) and 8-plex (Bio-Rad Laboratories) assay kits for human cytokines. Subjects were categorized based on EF as follows: ≥50% normal EF, 35-49% mild to moderately reduced EF and Results Fifty-nine patients were analyzed (97% male, mean age 70, range 57-89 years, 85% hypertensive, 66% diabetic, and 27% with reduced EF). Five soluble mediators inversely correlated with EF category: D-Dimer (r = -.27, p = .04), Ghrelin (r = -.29, p = .03), matrix metallopeptidase 3 (MMP3) (r = -.32, p = .01), high sensitivity C-Reactive Protein (hsCRP) (r = -.27, p = .04) and Eotaxin (r = -.28, p = .04). Conclusion Our results identified five plasma soluble mediators significantly inversely correlated with EF, including D-dimer, hsCRP, Ghrelin, MMP3 and Eotaxin. The association between cardiomyopathy and elevation of D-dimer, hsCRP, MMP3 and Ghrelin have been described previously. The association between eotaxin and cardiomyopathy in humans identified in our work is novel, although similar elevations have been suggested in an animal model of autoimmune response to cardiac troponin and subsequent myocardial fibrosis. Eotaxin is a C-C chemokine expressed by macrophages and cardiac fibroblasts and is thought to facilitate eosinophil trafficking to the heart. Further study in larger sample sizes is warranted to confirm our results and further elucidate mechanisms involved.