Τίτλος:
Differences in biomarkers and molecular pathways according to age for
patients with HFrEF
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Aims Elderly patients with heart failure with reduced ejection fraction
(HFrEF) have worse prognosis and less often receive
guideline-recommended therapies. We aim to better understand the
underlying pathophysiological processes associated with ageing in HFrEF
potentially leading to targeted therapies in this vulnerable population.
Methods and results From a panel of 363 cardiovascular biomarkers
available in 1611 patients with HFrEF in the BIOSTAT-CHF index cohort
and cross-validated in 823 patients in the BIOSTAT-CHF validation
cohort, we tested which biomarkers were dysregulated in patients aged
>75 vs. <65years. Second, pathway overrepresentation analyses were
performed to identify biological pathways linked to higher plasma
concentrations of biomarkers in elderly vs. younger patients. After
adjustment, multiple test correction [false discovery rate (FDR) 1%],
and cross-validation, 27/363 biomarkers were associated with older age,
22 positively and 5 negatively. The biomarkers that were positively
associated with older age were associated with tumour cell regulation,
extra-cellular matrix organization, and inflammatory processes, whereas
biomarkers negatively associated with older age were associated with
pathways that may point to cell proliferation and tumourigenesis. Among
the 27 biomarkers, WFDC2 (WAP four-disulphide core domain protein
2)-that broadly functions as a protease inhibitor-was associated with
older age and had the strongest association with all outcomes. No
protein-by-sex interaction was observed.
Conclusions In elderly HFrEF patients, pathways associated with
extra-cellular matrix organization, inflammatory processes, and tumour
cell regulation were activated, while pathways associated with tumour
proliferation functions were down-regulated. These findings may help in
a better understanding of the ageing processes in HFrEF and identify
potential therapeutic targets.
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Συγγραφείς:
Ferreira, Joao Pedro
Ouwerkerk, Wouter
Santema, Bernadet T. and
van Veldhuisen, Dirk J.
Lang, Chim C.
Ng, Leong L.
Anker,
Stefan D.
Dickstein, Kenneth
Metra, Marco
Cleland, John G.
F.
Nilesh, Samani J.
Filippatos, Gerasimos
Aboumsallem,
Joseph-Pierre
de Boer, Rudolf A.
Figarska, Sylwia
Sama,
Iziah E.
Voors, Adriaan A.
Zannad, Faiez
Περιοδικό:
Cardiovascular Research
Εκδότης:
Oxford University Press
Λέξεις-κλειδιά:
Ageing; Chronological age; Biological age; Biomarkers; Heart failure
with reduced ejection fraction
