The CCL+CD+ myocardial fibrosis phenotype was associated with an increased risk of heart failure hospitalization or cardiovascular death compared with the CCL-CD- phenotype (HR 2.18; P=0.04).
Cohort (n=241)
Do circulating biomarkers of collagen cross-linking and deposition identify myocardial fibrosis phenotypes with distinct clinical outcomes in hypertensive patients with heart failure?
The combination of low serum CITP:MMP-1 ratio and high serum PICP identifies a high-risk myocardial fibrosis phenotype in hypertensive heart failure patients associated with poor clinical outcomes.
Hazard Ratio: 2.18
p-value: p=0.04
OBJECTIVE: Myocardial fibrosis is associated with alterations in the cross-linking and deposition of collagen type I (CCL and CD, respectively). We aimed to evaluate whether the combination of circulating biomarkers of CCL the carboxy-terminal telopeptide of collagen type I to matrix metalloproteinase-1 ratio (CITP : MMP-1) and CD the carboxy-terminal propeptide of procollagen type I (PICP) identifies myocardial fibrosis phenotypes with distinct clinical outcome in hypertensive patients with heart failure. METHODS: Endomyocardial biopsies and blood samples from 38 patients (small cohort), and blood samples from 203 patients (large cohort) were analyzed. Myocardial CCL and CD were assessed by histological methods. Serum PICP, CITP, and MMP-1 were determined by ELISA. RESULTS: Small cohort: CITP : MMP-1 cutoff 1.968 or less and PICP cutoff at least 110.8 ng/ml were used for predicting high CCL and severe CD, respectively. Large cohort: as defined by the above thresholds, patients were categorized into four subgroups based on the presence (+) or absence (-) of high CCL and severe CD. Compared with CCL-CD-, the adjusted hazard ratios for a composite end point of heart failure hospitalization or cardiovascular death over 5 years in CCL-CD+, CCL+CD-, and CCL+CD+ were 1.11 (P = 0.79), 1.99 (P = 0.07), and 2.18 (P = 0.04), respectively (P for trend = 0.005). In addition, the categorization based on CCL and CD yielded integrated discrimination (P = 0.03) and net reclassification (P = 0.01) improvements for the mentioned outcome. CONCLUSION: The combination of low serum CITP : MMP-1 ratio and high serum PICP identifies hypertensive patients with heart failure presenting with a phenotype of myocardial fibrosis characterized by the concurrence of excessive CCL and CD and associated with poor outcome.
Ravassa et al. (Thu,) conducted a cohort in hypertensive patients with heart failure (n=241). CCL+CD+ myocardial fibrosis phenotype vs. CCL-CD- phenotype was evaluated on composite end point of heart failure hospitalization or cardiovascular death (HR 2.18, p=0.04). The CCL+CD+ myocardial fibrosis phenotype was associated with an increased risk of heart failure hospitalization or cardiovascular death compared with the CCL-CD- phenotype (HR 2.18; P=0.04).