Heart failure in obesity: insights from proteomics in patients treated with or without weight-loss surgery.
Journal
International journal of obesity (2005)
ISSN: 1476-5497
Titre abrégé: Int J Obes (Lond)
Pays: England
ID NLM: 101256108
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
01
02
2022
accepted:
11
07
2022
revised:
07
07
2022
pubmed:
10
8
2022
medline:
24
11
2022
entrez:
9
8
2022
Statut:
ppublish
Résumé
Obesity is associated with incident heart failure (HF), but the underlying mechanisms are unclear. We performed a nested case-control study within the Swedish-Obese-Subjects study, by identifying 411 cases who developed HF and matched them with respect to age, sex, weight-loss-surgery and length of follow-up with 410 controls who did not develop HF. In analyses corrected for multiple testing, we studied 182 plasma proteins known to be related to cardiovascular disease to investigate whether they could add to the understanding of the processes underlying obesity-related HF. A total of 821 subjects were followed for 16 ± 6 years. Multivariable analysis adjusted for matching variables revealed that 32 proteins were significantly associated with HF. Twelve proteins were related to HF ≥ 80% of the time using a bootstrap resampling approach (false-discovery-rate [FDR] < 0.05): 11 were associated with increased HF-risk: TNFRSF10A*, ST6GAL1, PRCP, MMP12, TIMP1, CCL3, QPCT, ANG, C1QTNF1, SERPINA5 and GAL-9; and one was related to reduced HF-risk: LPL. An further 20 proteins were associated with onset of HF 50-80% of the time using bootstrap resampling (FDR < 0.05). A pathway analysis including all significant 32 proteins suggested that these biomarkers were related to inflammation, matrix remodeling, cardiometabolic hormones and hemostasis. Three proteins, C1QTNF1, FGF-21 and CST3, reflecting dyslipidemia and kidney disease, displayed a higher association with HF in patients who did not undergo weight-loss-surgery and maintained with obesity. Pathways associated with HF in obesity include inflammation, matrix remodeling, cardiometabolic hormones and hemostasis; three protein biomarkers predicting HF appeared to be obesity-specific.
Sections du résumé
BACKGROUND
Obesity is associated with incident heart failure (HF), but the underlying mechanisms are unclear.
METHODS
We performed a nested case-control study within the Swedish-Obese-Subjects study, by identifying 411 cases who developed HF and matched them with respect to age, sex, weight-loss-surgery and length of follow-up with 410 controls who did not develop HF. In analyses corrected for multiple testing, we studied 182 plasma proteins known to be related to cardiovascular disease to investigate whether they could add to the understanding of the processes underlying obesity-related HF.
RESULTS
A total of 821 subjects were followed for 16 ± 6 years. Multivariable analysis adjusted for matching variables revealed that 32 proteins were significantly associated with HF. Twelve proteins were related to HF ≥ 80% of the time using a bootstrap resampling approach (false-discovery-rate [FDR] < 0.05): 11 were associated with increased HF-risk: TNFRSF10A*, ST6GAL1, PRCP, MMP12, TIMP1, CCL3, QPCT, ANG, C1QTNF1, SERPINA5 and GAL-9; and one was related to reduced HF-risk: LPL. An further 20 proteins were associated with onset of HF 50-80% of the time using bootstrap resampling (FDR < 0.05). A pathway analysis including all significant 32 proteins suggested that these biomarkers were related to inflammation, matrix remodeling, cardiometabolic hormones and hemostasis. Three proteins, C1QTNF1, FGF-21 and CST3, reflecting dyslipidemia and kidney disease, displayed a higher association with HF in patients who did not undergo weight-loss-surgery and maintained with obesity.
CONCLUSION
Pathways associated with HF in obesity include inflammation, matrix remodeling, cardiometabolic hormones and hemostasis; three protein biomarkers predicting HF appeared to be obesity-specific.
Identifiants
pubmed: 35945262
doi: 10.1038/s41366-022-01194-0
pii: 10.1038/s41366-022-01194-0
pmc: PMC9678794
doi:
Substances chimiques
Biomarkers
0
Hormones
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2088-2094Informations de copyright
© 2022. The Author(s).
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