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Proteomic biomarkers and pathway analysis for progression to heart failure in three epidemiological representative
Anna Dieden1,2,3, Nicolas Girerd4,5, Filip Ottosson6
1Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Insights
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a key biomarker for identifying individuals with asymptomatic cardiac dysfunction and those at high risk for heart failure (HF). This finding supports its clinical use and highlights potential therapeutic targets for HF prevention.
Area of Science:
- Cardiology
- Proteomics
- Biomarker Discovery
Background:
- Asymptomatic ventricular dysfunction poses a risk for heart failure (HF).
- Identifying reliable biomarkers can improve risk stratification and understanding of HF pathways.
- Proteomic biomarkers are being investigated for their association with cardiac dysfunction.
Purpose of the Study:
- To explore the association between proteomic biomarkers and left ventricular hypertrophy (LVH), diastolic dysfunction (DD), and incident HF.
- To validate findings across multiple population-based cohorts.
- To identify potential therapeutic targets for HF.
Main Methods:
- Measured 92 protein biomarkers in blood samples from over 1500 participants in the Malmö Preventive Project (MPP) cohort.
- Confirmed findings in the STANISLAS and HOMAGE case-control cohorts.
- Utilized multivariable logistic and Cox regression analyses, adjusting for cardiovascular risk factors.
Main Results:
- N-terminal pro-B-type natriuretic peptide (NT-proBNP) was significantly associated with LVH, DD, and incident HF across all cohorts.
- Galectin-4, growth differentiation factor 15, and suppression of tumorigenicity-2 were associated with incident HF in MPP and HOMAGE cohorts.
- Pathway enrichment analysis suggested links between inflammation, viral infection, and incident HF.
Conclusions:
- NT-proBNP is a crucial biomarker for asymptomatic cardiac dysfunction and incident HF, reinforcing its clinical utility.
- The study highlights NT-proBNP's value in identifying high-risk patients for HF.
- Findings provide insights into HF pathogenesis and potential therapeutic strategies.
Aims:
Biomarkers associated with asymptomatic ventricular dysfunction might improve risk stratification and identify pathways leading to heart failure (HF). We explored the association between proteomic biomarkers and left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and incident HF in three population-based cohorts.
Methods And Results:
A chip was used to measure 92 protein biomarkers in blood samples from >1500 Malmö Preventive Project (MPP) participants, of whom 514 had LVH (34%), 462 had DD (32.4%) and, over a median follow-up of 13 (11-14) years, 130 developed HF (7.7%). Findings were confirmed in the STANISLAS (n > 1500, 238 participants with LVH, 76 with DD) and HOMAGE case-control (562 cases of incident HF, 871 controls) cohorts. In multivariable logistic or Cox regression analyses adjusted for age, sex and cardiovascular risk factors, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with LVH, DD and incident HF in all cohorts: MPP (LVH odds ratio [OR] [95% confidence interval] 1.48 [1.28-1.71]; DD OR 1.71 [1.53-1.92]; HF HR 1.98 [1.66-2.36]); STANISLAS (LVH OR 1.20 [1.02-1.41]; DD OR 1.46 [1.12-1.90]); HOMAGE (HF HR 1.85 [1.62-2.12]). Galectin-4, growth differentiation factor 15 and suppression of tumorigenicity-2 were associated with incident HF in MPP and HOMAGE. A pathway enrichment analysis suggested that inflammation and viral infection were related to incident HF.
Conclusion:
In conclusion, our study reinforces the role of NT-proBNP as a key biomarker for asymptomatic cardiac dysfunction and incident HF, consistent with its established use in clinical practice. This underscores the value of NT-proBNP for identifying patients at high risk for HF, and provides insights into pathways leading to HF and potential therapeutic targets.
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