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. 2022 Dec;46(12):2088-2094.
doi: 10.1038/s41366-022-01194-0. Epub 2022 Aug 9.

Heart failure in obesity: insights from proteomics in patients treated with or without weight-loss surgery

Kristjan Karason  1   2 , Nicolas Girerd  3 , Johanna Andersson-Asssarsson  4 , Kevin Duarte  3 , Magdalena Taube  4 , Per-Arne Svensson  4   5 , Anne-Cecile Huby  3 , Markku Peltonen  6 , Lena M Carlsson  4 , Faiez Zannad  3
Affiliations

Heart failure in obesity: insights from proteomics in patients treated with or without weight-loss surgery

Kristjan Karason et al. Int J Obes (Lond). 2022 Dec.

Abstract

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.

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Conflict of interest statement

KK has received lecture fees from Orion Pharma AB and Abbot. LMC has received consulting fees from Johnson & Johnson. MT holds stocks in Umecrine AB, and has a patent licensed to Umecrine AB. FZ reports steering committee personal fees from Applied Therapeutics, Bayer, Boehringer, Boston Scientific, Novartis, Janssen, Cellprothera and CVRx, advisory board personal fees from, AstraZeneca, Vifor Fresenius, Cardior, Cereno pharmaceutical, Corvidia, Merck, Myokardia, NovoNordisk and Owkin, stock options at Cereno and G3Pharmaceutical, and being the founder of CardioRenal and the Global Cardiovascular Clinical Trialist Forum. None of the remaining authors have any conflicts of interest ties to disclose.

Figures

Fig. 1
Fig. 1. Changes in BMI in the two study groups during follow-up.
Changes in BMI over time for A cases (n = 411) and B matched controls (n = 410) treated with and without bariatric surgery, respectively.
Fig. 2
Fig. 2. A correlation heatmap depicting the strength of relationships between protein biomarkers and incident HF.
A heatmap based on Spearman correlations between the 12 essential protein BMs associated with HF development with an FDR < 5% and retained during 80% or more of the time according to the bootstrap resampling approach resampling approach.
Fig. 3
Fig. 3. A network analysis illustrating the links among proteins associated with heart failure.
A network analysis based on 32 proteins associated with HF more than 50% of the time according to the resample approach.
See this image and copyright information in PMC

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