Although NT-proBNP, troponin, and hs-CRP are detectable in saliva, salivary measurements of NT-proBNP and troponin showed insufficient agreement with serum levels to support their use as substitutes for blood-based assessment in heart failure, while hs-CRP demonstrated comparatively better performance but remains limited by variability.
Key Findings
Results
All three cardiovascular biomarkers (NT-proBNP, troponin, and hs-CRP) were consistently detectable in whole saliva samples from heart failure patients.
Biomarkers were detectable at all three time points: baseline, 3 months, and 6 months
The study population included 52 individuals (30 males and 22 females) with HFmrEF (LVEF 41-49%) or HFrEF (LVEF ≤40%)
Participants were aged 49-80 years with a mean age of 61.1 ± 6.79 years
Paired saliva and blood samples were collected prospectively at each time point
Results
Salivary NT-proBNP did not demonstrate clinically acceptable agreement with serum concentrations at any evaluated time point.
Bland-Altman analyses were used to assess agreement between salivary and serum measurements
The lack of agreement was consistent across all three time points (baseline, 3 months, and 6 months)
Findings indicated limited interchangeability between salivary and serum matrices for NT-proBNP
NT-proBNP is a key biomarker used in heart failure diagnosis and monitoring
Results
Salivary troponin did not demonstrate clinically acceptable agreement with serum concentrations at any evaluated time point.
Bland-Altman analyses revealed insufficient agreement between salivary and serum troponin at all time points
Findings indicated limited interchangeability between matrices for troponin
This was consistent across baseline, 3-month, and 6-month assessments
Results do not support the use of salivary troponin as a substitute for blood-based assessment in heart failure
Results
High-sensitivity C-reactive protein (hs-CRP) exhibited relatively better agreement between saliva and serum compared to the other two biomarkers.
Bland-Altman analysis showed mean bias close to zero for hs-CRP
Limits of agreement were described as 'moderate' for hs-CRP
Substantial inter-individual variability persisted despite the better mean agreement
hs-CRP's better performance still did not fully support substitution of serum measurements with salivary measurements
Results
Age and sex did not meaningfully influence the relationship between salivary and serum biomarker concentrations.
Additional analyses explicitly explored whether age influenced the salivary-serum biomarker relationship
Neither age nor sex were found to be meaningful modifying factors
The study population ranged from 49-80 years, providing a reasonable age range for this assessment
The sample included both males (n=30) and females (n=22)
Conclusions
Serum remains the reference standard for cardiovascular biomarker assessment in heart failure under the conditions evaluated.
The authors concluded that saliva 'should be regarded as a matrix warranting further investigation' rather than a current clinical substitute
The study design was prospective with a six-month follow-up period
The conclusion applied specifically to NT-proBNP and troponin, with hs-CRP noted as having comparatively better but still insufficient performance
The study assessed patients with reduced or mildly reduced ejection fraction (HFmrEF or HFrEF)
What This Means
This research suggests that while it is possible to detect heart failure biomarkers in saliva, saliva tests cannot currently replace blood tests for monitoring patients with heart failure. The study followed 52 heart failure patients over six months, collecting paired saliva and blood samples at three time points to measure three important heart-related proteins: NT-proBNP (a hormone released when the heart is under stress), troponin (a protein released when heart muscle is damaged), and high-sensitivity C-reactive protein (a marker of inflammation). Although all three proteins showed up in saliva, the saliva measurements for NT-proBNP and troponin did not match the blood measurements closely enough to be considered interchangeable.
Of the three biomarkers tested, the inflammation marker hs-CRP performed best in saliva, with its saliva levels on average closer to blood levels. However, there was still too much variation between individuals to make saliva a reliable substitute for blood testing. Notably, factors like a patient's age or sex did not appear to explain why saliva and blood measurements differed, meaning the inconsistency is not simply due to patient characteristics.
This research suggests that saliva-based cardiovascular testing is a promising area but is not yet ready for clinical use in heart failure management. Blood testing remains the standard approach. Future studies may need to explore whether standardizing saliva collection methods, using different saliva fractions, or studying larger and more diverse patient groups could improve the reliability of salivary biomarker measurements.
Melo Viegas R, Cortelli S, Romeiro Aquino D, Costa F, Hentges B, Pádua de Magalhães V, et al.. (2026). Salivary and serum levels of NT-proBNP, troponin, and high-sensitivity C-reactive protein in patients with heart failure.. PloS one. https://doi.org/10.1371/journal.pone.0357206