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The impact of myocardial fibrosis biomarkers in a heart failure population with atrial fibrillation—The HARVEST-Malmö study

Nezami, Zainu LU ; Holm, Hannes LU ; Ohlsson, Marcus LU orcid ; Molvin, John LU ; Korduner, Johan LU ; Bachus, Erasmus LU ; Zaghi, Amir LU orcid ; Dieden, Anna LU orcid ; Platonov, Pyotr LU and Jujic, Amra LU , et al. (2022) In Frontiers in Cardiovascular Medicine 9. p.1-11
Abstract
Background: Several studies suggest that circulating biomarkers of myocardial fibrosis are associated with worse prognosis in subjects with atrial fibrillation (AF). Here, we aimed to explore associations between fibrosis biomarkers, prevalent AF, and left atrial volume (LAV) enlargement in subjects with heart failure (HF). Additionally, we evaluated the prognostic impact of fibrotic biomarkers in HF with co-existing AF.

Materials and methods: Patients hospitalized for HF (n = 316, mean age 75 years; 30% women) were screened for AF. Seven proteins previously associated with myocardial fibrosis [metalloproteinase inhibitor 4 (TIMP-4), suppression of tumorigenicity 2 (ST-2), galectin-3 (GAL-3), growth/differentiation factor-15... (More)
Background: Several studies suggest that circulating biomarkers of myocardial fibrosis are associated with worse prognosis in subjects with atrial fibrillation (AF). Here, we aimed to explore associations between fibrosis biomarkers, prevalent AF, and left atrial volume (LAV) enlargement in subjects with heart failure (HF). Additionally, we evaluated the prognostic impact of fibrotic biomarkers in HF with co-existing AF.

Materials and methods: Patients hospitalized for HF (n = 316, mean age 75 years; 30% women) were screened for AF. Seven proteins previously associated with myocardial fibrosis [metalloproteinase inhibitor 4 (TIMP-4), suppression of tumorigenicity 2 (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)] were analyzed using a proximity extension assay. Proteins with significant Bonferroni-corrected associations with mortality and re-hospitalization risk were taken forward to multivariable Cox regression analyses. Further, Bonferroni-corrected multivariable logistic regression models were used to study associations between protein plasma levels, prevalent AF, and severely enlarged left atrial volume index (LAVI ≥ 48 ml/m2).

Results: Prevalent AF was observed in 194 patients at the hospitalization of whom 178 (92%) were re-hospitalized and 111 (57%) died during the follow-up period. In multivariable logistic regression models, increased plasma levels of TIMP-4, GDF-15, and ST-2 were associated with the prevalence of AF, whereas none of the seven proteins showed any significant association with severely enlarged LAVI. Increased plasma levels of five proteins yielded significant associations with all-cause mortality in patients with co-existing AF; TIMP-4 (HR 1.33; CI95% 1.07–1.66; p = 0.010), GDF-15 (HR 1.30; CI95% 1.05–1.62; p = 0.017), GAL-3 (HR 1.29; CI95% 1.03–1.61; p = 0.029), ST-2 (HR 1.48; CI95% 1.18–1.85; p < 0.001), and MMP-3 (HR 1.33; CI95% 1.09–1.63; p = 0.006). None of the proteins showed any significant association with re-hospitalization risk.

Conclusion: In this study, we were able to demonstrate that elevated levels of three plasma proteins previously linked to myocardial fibrosis are associated with prevalent AF in a HF population. Additionally, higher levels of five plasma proteins yielded an increased risk of mortality in the HF population with or without co-existing AF. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Frontiers in Cardiovascular Medicine
volume
9
article number
982871
pages
1 - 11
publisher
Frontiers Media S. A.
external identifiers
  • pmid:36337899
  • scopus:85141127299
ISSN
2297-055X
DOI
10.3389/fcvm.2022.982871
language
English
LU publication?
yes
id
e9b51284-83ce-4ca4-9dee-1d2dc0ac3975
date added to LUP
2022-10-20 13:32:26
date last changed
2023-12-07 01:24:00
@article{e9b51284-83ce-4ca4-9dee-1d2dc0ac3975,
  abstract     = {{Background: Several studies suggest that circulating biomarkers of myocardial fibrosis are associated with worse prognosis in subjects with atrial fibrillation (AF). Here, we aimed to explore associations between fibrosis biomarkers, prevalent AF, and left atrial volume (LAV) enlargement in subjects with heart failure (HF). Additionally, we evaluated the prognostic impact of fibrotic biomarkers in HF with co-existing AF.<br/><br/>Materials and methods: Patients hospitalized for HF (n = 316, mean age 75 years; 30% women) were screened for AF. Seven proteins previously associated with myocardial fibrosis [metalloproteinase inhibitor 4 (TIMP-4), suppression of tumorigenicity 2 (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)] were analyzed using a proximity extension assay. Proteins with significant Bonferroni-corrected associations with mortality and re-hospitalization risk were taken forward to multivariable Cox regression analyses. Further, Bonferroni-corrected multivariable logistic regression models were used to study associations between protein plasma levels, prevalent AF, and severely enlarged left atrial volume index (LAVI ≥ 48 ml/m2).<br/><br/>Results: Prevalent AF was observed in 194 patients at the hospitalization of whom 178 (92%) were re-hospitalized and 111 (57%) died during the follow-up period. In multivariable logistic regression models, increased plasma levels of TIMP-4, GDF-15, and ST-2 were associated with the prevalence of AF, whereas none of the seven proteins showed any significant association with severely enlarged LAVI. Increased plasma levels of five proteins yielded significant associations with all-cause mortality in patients with co-existing AF; TIMP-4 (HR 1.33; CI95% 1.07–1.66; p = 0.010), GDF-15 (HR 1.30; CI95% 1.05–1.62; p = 0.017), GAL-3 (HR 1.29; CI95% 1.03–1.61; p = 0.029), ST-2 (HR 1.48; CI95% 1.18–1.85; p &lt; 0.001), and MMP-3 (HR 1.33; CI95% 1.09–1.63; p = 0.006). None of the proteins showed any significant association with re-hospitalization risk.<br/><br/>Conclusion: In this study, we were able to demonstrate that elevated levels of three plasma proteins previously linked to myocardial fibrosis are associated with prevalent AF in a HF population. Additionally, higher levels of five plasma proteins yielded an increased risk of mortality in the HF population with or without co-existing AF.}},
  author       = {{Nezami, Zainu and Holm, Hannes and Ohlsson, Marcus and Molvin, John and Korduner, Johan and Bachus, Erasmus and Zaghi, Amir and Dieden, Anna and Platonov, Pyotr and Jujic, Amra and Magnusson, Martin}},
  issn         = {{2297-055X}},
  language     = {{eng}},
  pages        = {{1--11}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Cardiovascular Medicine}},
  title        = {{The impact of myocardial fibrosis biomarkers in a heart failure population with atrial fibrillation—The HARVEST-Malmö study}},
  url          = {{http://dx.doi.org/10.3389/fcvm.2022.982871}},
  doi          = {{10.3389/fcvm.2022.982871}},
  volume       = {{9}},
  year         = {{2022}},
}