Abstract
Introduction: Several studies suggest that circulating biomarkers of myocardial fibrosis are associated with worse prognosis of atrial fibrillation (AF). Hypothesis: Here, we aimed to evaluate the prognostic impact of myocardial fibrosis biomarkers for atrial fibrillation in a heart failure (HF) population Methods: Three-hundred-and-twenty-one patients hospitalized for HF (mean age 75 years; 32% women) were screened for co-existing AF and a proximity extension assay including estimation of 7 proteins associated with myocardial fibrosis; Metalloproteinase inhibitor 4 (TIMP-4), Soluble interleukin 1 receptor-like 1 (ST-2), Galectin 3 (Gal-3), Growth/differentiation factor 15 (GDF-15) and Matrix metalloproteinase 2, 3 and 9 (MMP-3, MMP-3 and MMP-9 respectively). Associations between AF and proteins were cross-sectionally studied in multivariable logistic regression models. Furthermore, associations between protein plasma levels, mortality and re-hospitalization risk were analyzed using multivariable Cox regression analysis adjusted for age sex, prevalent diabetes, smoking, body mass index (BMI), systolic blood pressure (SBP) and New York heart association classification (NYHA-class). Results: One-hundred-and-ninety-seven patients (61%) had prevalent AF at hospitalization. In multivariate logistic regression models, the prevalence of atrial fibrillation was significantly associated with increased plasma levels of TIMP-4, GDF-15, ST-2, MMP-2 and MMP-9. In the fully adjusted Cox regression model, increased plasma levels of 5 proteins yielded significant associations with mortality; TIMP4 (p=0,022 HR;1,46 CI95%1,06-2,01), GDF 15 (p=0,028; HR1,29; CI95% 1,03-1,63), Gal-3 (p=0,017; HR1,64;CI95% 1,09-2,47), ST2 (p=0,002; HR;1,43; CI95%1,14-1,80) and MMP3 (p=0,011; HR;1,29; CI95% 1,06-1,58). Further, increased levels of TIMP4 was significantly associated with rehospitalization (p=0,001; HR 1,58; C95% 1,19-2,08). Conclusions: We have demonstrated that increased plasma levels of plasma proteins related to myocardial fibrosis are associated with the risk of mortality in hospitalized HF patients, independently of traditional risk factors.
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