Post-discharge assessment of collagen formation biomarkers in individuals with HFpEF hospitalized for decompensated heart failure
E Angeli, E Revuelta Lopez, M Karsdal, F Genovese, A Bayes-GenisAbstract
Background
Circulating collagen fragments may reflect subclinical pathological processes and hold potential as tools for improved clinical assessment. Collagen biomarkers in circulation have previously demonstrated prognostic value for adverse outcome in cardiovascular diseases, particularly in heart failure with preserved ejection fraction (HFpEF).
Purpose
This study aimed to assess collagen formation dynamics in a cohort of patients after hospitalization for decompensated heart failure, using measurements obtained at two time points.
Methods
Collagen formation was quantified with four enzyme-linked immunosorbent assays (ELISA) targeting specific epitopes of collagen type V (PRO-C5), collagen type VI (PRO-C6 and Endotrophin)and collagen type VII (PRO-C7). We assessed serum samples from 650 individuals, recruited from a structured multidisciplinary post-discharge outpatient program for vulnerable patients hospitalized with decompensated HFpEF. Patients were evaluated within one week after hospital discharge and followed for approximately one month, with systematic collection data at baseline and at discharge from the program. Biomarker concentrations were log2-transformed prior to analysis. Differences between the two time points were assessed using the Wilcoxon signed-rank test. Unadjusted and multivariable-adjusted logistic regression models were used to evaluate associations with all-cause mortality.
Results
Among the four biomarkers assessed at one week and one-month post-discharge, PRO-C6 and Endotrophin demonstrated a significant increase (p<0.001) during the first month following hospitalization for decompensated heart failure, whereas median levels of PRO-C7 significantly decreased over the same period (p=0.03). PRO-C5 showed no significant temporal change (p=0.21). At baseline, PRO-C6, Endotrophin and PRO-C5 remained significantly associated with the risk of all-cause mortality even after multivariable adjustment for age, sex, left ventricular ejection fraction (LVEF), body mass index (BMI), and NT-proBNP. Both collagen type VI biomarkers, PRO-C6 and Endotrophin, were independently associated with an increased risk of mortality (odds ratio [OR] 1.39, p = 0.02; OR 1.31, p = 0.03), whereas PRO-C5 was inversely associated with mortality risk (OR 0.33, p < 0.001). PRO-C7 was not significantly associated with outcome.
Conclusion
In patients with HFpEF recently hospitalized for decompensated heart failure, collagen formation biomarkers exhibit dynamic changes early after discharge and are independently associated with all-cause mortality. The observed associations suggest that markers of extracellular matrix remodelling may capture complementary pathophysiological information beyond established clinical risk factors. These findings support further investigation of collagen turnover biomarkers as components of multidimensional risk stratification in HFpEF.