Metabolomics and a Breath Sensor Identify Acetone as a Biomarker for Heart Failure
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Hypotheses
2.3. Biomarkers
2.4. GCMS
2.5. LCMS
2.6. Volatilomics
2.7. Statistics
3. Results
3.1. Metabolomics
3.2. Volatilomics
3.3. Pathway and Network Analysis
4. Discussion
5. Limitations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
References
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HF N = 46 | Control N = 20 | p Value | |
---|---|---|---|
Age, mean (SD) | 68 (8) | 52 (9) | 5 × 10−9 |
Male, n (%) | 41 (89) | 10 (50) | 0.0006 |
European | 29 (63) | 16 (80) | 0.18 |
AF | 10 (22) | 0 (0) | N/A |
HTN | 21 (46) | 0 (0) | N/A |
T2Dm | 9 (20) | 0 (0) | N/A |
ACEi/ARB | 37 (80) | 0 (0) | N/A |
Beta blocker | 39 (85) | 0 (0) | N/A |
MRA | 14 (3) | 0 (0) | N/A |
Statin | 29 (63) | 0 (0) | N/A |
Frusemide | 10 (22) | 0 (0) | N/A |
EF bp mean (SD) | 39% (10 | 57% (5) | 8 × 10−9 |
GLS | −13% (0.04) | −21% (0.05) | 3 × 10−8 |
NTproBNP (pmol/L) | 115 (124) | 8 (10) | 0.0002 |
Metabolite | Tstat | p Value | = –LOG(10p) | FDR |
---|---|---|---|---|
Cis-Aconitic Acid | −5.44 | 9.09 × 10−7 | 6.04 | 9.25 × 10−5 |
Isocitric acid | −5.35 | 1.28 × 10−6 | 5.89 | 9.25 × 10−5 |
Glutathione | −4.87 | 7.56 × 10−6 | 5.12 | 2.81 × 10−4 |
Unknown 115100 5965.5 18950.1 | −4.87 | 7.76 × 10−6 | 5.11 | 2.81 × 10−4 |
Citric acid | −4.43 | 3.76 × 10−5 | 4.42 | 1.09 × 10−3 |
DL-gamma-methyl-ketoglutaramate | −4.31 | 5.77 × 10−5 | 4.24 | 1.39 × 10−3 |
4-Hydroxyphenylacetic acid | −4.11 | 1.16 × 10−4 | 3.93 | 2.11 × 10−3 |
Linoleic acid C18_2n-6,9c | 4.12 | 1.57 × 10−4 | 3.80 | 1.62 × 10−2 |
Beta-Alanine | −3.96 | 1.89 × 10−4 | 3.72 | 6.84 × 10−3 |
Fumaric acid | −3.96 | 1.90 × 10−4 | 3.72 | 3.06 × 10−3 |
Cis-Vaccenic acid C18_1n-7c | 4.01 | 2.23 × 10−4 | 3.65 | 1.62 × 10−2 |
Unknown 113100 8548.1 5921.2 | −3.84 | 2.80 × 10−4 | 3.55 | 3.51 × 10−3 |
Malic acid | −3.84 | 2.89 × 10−4 | 3.54 | 3.51 × 10−3 |
Unknown 127100 15949.8 5948.8 | −3.56 | 7.02 × 10−4 | 3.15 | 6.37 × 10−3 |
Itaconic acid | −3.76 | 3.72 × 10−4 | 3.43 | 4.15 × 10−3 |
Unknown 114100 14731.9 11527.2 | −3.61 | 6.07 × 10−4 | 3.22 | 5.87 × 10−3 |
Pentadecanoic acid C15_0 | 3.67 | 6.35 × 10−4 | 3.20 | 2.65 × 10−2 |
Unknown 125100 18490.5 9654.3 | −3.56 | 7.02 × 10−4 | 3.15 | 6.37 × 10−3 |
Ornithine | −3.36 | 1.32 × 10−3 | 2.88 | 1.12 × 10−2 |
Cysteine | −3.41 | 1.35 × 10−3 | 2.87 | 3.23 × 10−2 |
11,14-Eicosadienoic C20_2n-6,9c | 3.34 | 1.67 × 10−3 | 2.78 | 3.46 × 10−2 |
Malonic acid | −3.28 | 1.71 × 10−3 | 2.77 | 1.37 × 10−2 |
Glutamic acid | −3.19 | 2.22 × 10−3 | 2.65 | 4.03 × 10−2 |
Succinic acid | −3.14 | 2.55 × 10−3 | 2.59 | 1.95 × 10−2 |
Arachidic acid C20_0 | 3.17 | 2.68 × 10−3 | 2.65 | 4.03 × 10−2 |
2-Hydroxyisobutyric acid | −3.04 | 3.41 × 10−3 | 2.47 | 2.47 × 10−2 |
Unknown 128100 13921.1 4219.1 | −2.85 | 5.87 × 10−3 | 2.23 | 3.87 × 10−2 |
Adipic acid | −2.78 | 7.07 × 10−3 | 2.15 | 4.46 × 10−2 |
Metabolite | Tstat | p Value | = –LOG(10p) | FDR |
---|---|---|---|---|
Symmetric dimethylarginine | −5.31 | 1.65 × 10−6 | 5.78 | 7.11 × 10−5 |
Cholesteryl ester (18:2) | 5.06 | 4.15 × 10−6 | 5.38 | 9.13 × 10−4 |
Sphingomyelin (42:1) | 4.91 | 7.19 × 10−6 | 5.14 | 8.13 × 10−4 |
Sphingomyelin (40:4) | 4.82 | 1.00 × 10−5 | 5.00 | 8.13 × 10−4 |
Sphingomyelin (38:1) | 4.52 | 2.88 × 10−5 | 4.54 | 1.75 × 10−3 |
Triglyceride (55:9) | −4.52 | 2.91 × 10−5 | 4.09 | 7.07 × 10−3 |
Sphingomyelin (40:2) | 4.23 | 8.05 × 10−5 | 4.09 | 3.91 × 10−3 |
Creatinine | −4.22 | 8.44 × 10−5 | 4.07 | 1.82 × 10−3 |
Sphingomyelin (40:1) | 4.06 | 1.44 × 10−4 | 3.84 | 3.51 × 10−2 |
Sphingomyelin (33:2) | 4.04 | 1.50 × 10−4 | 3.82 | 6.06 × 10−3 |
Phosphatidylcholine (34:5) | 3.98 | 2.18 × 10−4 | 3.66 | 2.01 × 10−2 |
Lysophosphatidylcholine (18:2) | 3.89 | 2.53 × 10−4 | 3.60 | 8.77 × 10−3 |
Phosphatidylcholine (30:0) | 3.90 | 2.80 × 10−4 | 3.55 | 2.01 × 10−2 |
Sphingomyelin (33:1) | 3.89 | 2.94 × 10−4 | 3.53 | 2.01 × 10−2 |
Phosphatidylcholine (30:0) | 3.81 | 3.79 × 10−4 | 3.42 | 2.15 × 10−2 |
Phosphatidylcholine (39:3) | 3.75 | 3.89 × 10−4 | 3.41 | 1.18 × 10−2 |
Phosphatidylcholine (35:5) | 3.60 | 6.31 × 10−4 | 3.20 | 1.67 × 10−2 |
Phosphatidylcholine (34:2) | 3.56 | 7.30 × 10−4 | 3.14 | 1.67 × 10−2 |
Phosphatidylcholine (32:3) | 3.52 | 8.13 × 10−4 | 3.09 | 1.67 × 10−2 |
Phosphatidylcholine (36:5) | 3.52 | 8.25 × 10−4 | 3.08 | 1.67 × 10−2 |
Phosphatidylcholine (36:2) | 3.49 | 1.00 × 10−3 | 3.00 | 3.28 × 10−2 |
Arginine | 3.41 | 1.18 × 10−3 | 2.93 | 4.40 × 10−2 |
Sphingomyelin (41:1) | 3.38 | 1.27 × 10−3 | 2.90 | 2.31 × 10−2 |
Sphingomyelin (39:1) | 3.35 | 1.40 × 10−3 | 2.85 | 2.31 × 10−2 |
Sphingomyelin (39:2) | 3.36 | 1.47 × 10−3 | 2.83 | 3.85 × 10−2 |
Sphingomyelin (41:2) | 3.35 | 1.54 × 10−3 | 2.81 | 3.85 × 10−2 |
Sphingomyelin (38:2) | 3.31 | 1.56 × 10−3 | 2.81 | 3.85 × 10−2 |
Phosphatidylcholine (32:2) | 3.34 | 1.58 × 10−3 | 2.80 | 3.85 × 10−2 |
Kynurenine | −3.25 | 1.91 × 10−3 | 2.72 | 2.74 × 10−2 |
Sphingomyelin (31:1) | 3.25 | 2.05 × 10−3 | 2.69 | 4.65 × 10−2 |
Cholesteryl ester (16:0) | 3.09 | 2.98 × 10−3 | 2.53 | 4.07 × 10−2 |
Lysophosphatidylcholine (16:0) | 3.06 | 3.26 × 10−3 | 2.49 | 4.17 × 10−2 |
Lysophosphatidylcholine (18:0) | 3.00 | 3.94 × 10−3 | 2.50 | 4.49 × 10−2 |
Phosphatidylcholine (34:6) | 2.96 | 4.41 × 10−3 | 2.36 | 4.61 × 10−2 |
Lysophosphatidylcholine (15:0) | 2.95 | 4.55 × 10−3 | 2.34 | 4.61 × 10−2 |
Tstat | p Value | = –LOG10(p) | FDR | |
---|---|---|---|---|
Acetone | −6.0327 | 9.80 × 10−8 | 7.0088 | 1.08 × 10−5 |
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Gladding, P.A.; Cooper, M.; Young, R.; Loader, S.; Smith, K.; Zarate, E.; Green, S.; Villas Boas, S.G.; Shepherd, P.; Kakadiya, P.; et al. Metabolomics and a Breath Sensor Identify Acetone as a Biomarker for Heart Failure. Biomolecules 2023, 13, 13. https://doi.org/10.3390/biom13010013
Gladding PA, Cooper M, Young R, Loader S, Smith K, Zarate E, Green S, Villas Boas SG, Shepherd P, Kakadiya P, et al. Metabolomics and a Breath Sensor Identify Acetone as a Biomarker for Heart Failure. Biomolecules. 2023; 13(1):13. https://doi.org/10.3390/biom13010013
Chicago/Turabian StyleGladding, Patrick A., Maxine Cooper, Renee Young, Suzanne Loader, Kevin Smith, Erica Zarate, Saras Green, Silas G. Villas Boas, Phillip Shepherd, Purvi Kakadiya, and et al. 2023. "Metabolomics and a Breath Sensor Identify Acetone as a Biomarker for Heart Failure" Biomolecules 13, no. 1: 13. https://doi.org/10.3390/biom13010013