A Precision Medicine Approach to Natriuretic Peptide-Guided Risk Prediction and Treatment: A Retrospective Analysis in the STOP-HF Cohort
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2025-09-23Citation:
Claire Sweeney, 'A Precision Medicine Approach to Natriuretic Peptide-Guided Risk Prediction and Treatment: A Retrospective Analysis in the STOP-HF Cohort'Download Item:
Abstract:
Introduction: Individual studies show that NP-guided treatment is an effective intervention
for the prevention of HF. We hypothesised that this approach may be optimised utilising a
precision medicine approach.
Methods: A systematic literature review and meta-analysis were performed to establish the
effectiveness of NP-guided treatment versus standard care. The original research work uses
data from the STOP-HF cohort, a prospective, longitudinal study population comprising
patients over-40, with risk factors for developing HF. We evaluated the incremental benefit of
molar NT-proBNP/BNP ratio in predicting HF/LVD. We developed a genetic adjustment (GA)
score of genetic variants associated with NT-proBNP levels and cardioprotection (rs198389,
rs6676300, and rs13107325). We tested its association with outcomes and used it to generate
genetically adjusted NT-proBNP which was evaluated for the prediction of HF/LVD. Finally,
we defined a cohort of patients with Stage B HF and relatively low BNP (< 20 pg/mL) and
evaluated the clinical, genetic, and echocardiographic characteristics of these patients.
Results: The systematic review and meta-analysis indicate that NP-guided treatment is an
effective intervention for preventing cardiovascular and all-cause hospitalisation, and
ventricular dysfunction, although the effect on mortality is unclear. Molar NT-proBNP/BNP
ratio was inversely associated with risk of HF and/or LVD but did not improve risk prediction
metrics compared to individual NP measurements. The GA score was significantly associated
with risk of prevalent hypertension and left atrial volume index (LAVI), but did not improve
risk prediction for HF/LVD beyond standard NT-proBNP. Patients with Stage B HF and low
BNP were more likely to have a lower GA score and had earlier features of Stage B HF than
those with BNP > 20 pg/mL yet were still at risk due to increased LAVI.
Conclusions: Personalised approaches to NP-guided risk prediction using molar NT-
proBNP/BNP ratio and genetically adjusted NT-proBNP did not improve the prediction of
HF/LVD beyond current NP-based screening. GA score evaluation in HF prevention
programmes may help identify patients with relatively low BNP levels and Stage B HF who
would be missed according to current thresholds for referral for echocardiography.
Sponsor
Grant Number
HeartBeat Trust
Author: Sweeney, Claire
Advisor:
Ledwidge, MarkRyan, Cristín
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Doctor of PhilosophyType of material:
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Full text availableKeywords:
heart failure, natriuretic peptides, risk prediction, genetics, preventionMetadata
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