The association between collagen 1a1, NTproBNP and echocardiographic markers in patients with or at risk of HFpEF

Int J Cardiol. 2026 Mar 15:447:134109. doi: 10.1016/j.ijcard.2025.134109. Epub 2025 Dec 16.

Abstract

Aim: Plasma collagen 1a1 (Col-1a1), part of the α1 chain of collagen type-1, may be a marker of fibrosis in patients with heart failure (HF) and at increased risk of HF. We assessed associations amongst Col-1a1, NT-proBNP and echocardiographic parameters of cardiac structure and function and their relationship to prognosis in HFpEF.

Methods: We assessed 461 patients with HFpEF enrolled from the MEDIA-DHF cohort (mean age 74 [68, 80], 63 % women) and 516 those at risk of HF from the HOMAGE trial (mean age 73 [69, 79], 26 % women). Crude and adjusted linear regression models were used to evaluate the relationships amongst Col-1a1 (measured using proximity extension assay), NT-proBNP and echocardiographic measures. For the MEDIA-DHF study, the main outcome of interest was cardiovascular hospitalization and all-cause mortality.

Results: In both cohorts, patients with higher Col-1a1 levels were more likely to have poorer renal function, lower hemoglobin, higher NT-proBNP and lower prevalence of diabetes. In the MEDIA-DHF cohort, higher Col-1a1 was associated with higher NT-proBNP (β = 1.39; 95 %CI 1.08-1.80; p = 0.012), left atrial volume index (LAVi) (β = 4.57; 95 %CI 1.00-8.14; p = 0.013) and pulmonary artery systolic pressure (PAPs) (ß = 4.42; 95 %CI 1.47-7.37; p = 0.004). These results were corroborated in the HOMAGE trial: higher Col-1a1 was associated with higher NT-proBNP (ß = 0.20; 95 %CI 0.05-0.34; p = 0.009) and LAVi (ß = 2.32; 95 %CI 0.25-4.39; p = 0.028). Col-1a1 was not associated with the risk of the composite outcome in the MEDIA-DHF cohort.

Conclusion: Col-1a1 was associated with NT-proBNP and LAVi in HFpEF as well as in patients at high risk of HF but not with outcomes in HFpEF. Further studies are needed to understand what role, if any, Col-1a1 has as a marker of fibrosis or prognosis in patients with HFpEF.

Keywords: Col-1a1; Collagen metabolism; Echocardiography; Heart failure; LAVi.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Cohort Studies
  • Collagen Type I* / blood
  • Collagen Type I, alpha 1 Chain
  • Echocardiography* / methods
  • Echocardiography* / trends
  • Female
  • Follow-Up Studies
  • Heart Failure* / blood
  • Heart Failure* / diagnostic imaging
  • Heart Failure* / physiopathology
  • Humans
  • Male
  • Natriuretic Peptide, Brain* / blood
  • Peptide Fragments* / blood
  • Prognosis
  • Risk Factors
  • Stroke Volume / physiology

Substances

  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Biomarkers
  • Natriuretic Peptide, Brain
  • Collagen Type I, alpha 1 Chain
  • COL1A1 protein, human
  • Collagen Type I