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. 2023 Aug;112(8):1056-1066.
doi: 10.1007/s00392-023-02171-x. Epub 2023 Mar 30.

Systemic oxidative stress associates with disease severity and outcome in patients with new-onset or worsening heart failure

Marie-Sophie L Y de Koning  1 , Johanna E Emmens  2 , Esteban Romero-Hernández  3 , Arno R Bourgonje  4 , Solmaz Assa  2 , Sylwia M Figarska  2 , John G F Cleland  5   6 , Nilesh J Samani  7 , Leong L Ng  7 , Chim C Lang  8 , Marco Metra  9 , Gerasimos S Filippatos  10 , Dirk J van Veldhuisen  2 , Stefan D Anker  11 , Kenneth Dickstein  12 , Adriaan A Voors  2 , Erik Lipsic  2 , Harry van Goor  13 , Pim van der Harst  2   14
Affiliations

Systemic oxidative stress associates with disease severity and outcome in patients with new-onset or worsening heart failure

Marie-Sophie L Y de Koning et al. Clin Res Cardiol. 2023 Aug.

Abstract

Background: Oxidative stress may be a key pathophysiological mediator in the development and progression of heart failure (HF). The role of serum-free thiol concentrations, as a marker of systemic oxidative stress, in HF remains largely unknown.

Objective: The purpose of this study was to investigate associations between serum-free thiol concentrations and disease severity and clinical outcome in patients with new-onset or worsening HF.

Methods: Serum-free thiol concentrations were determined by colorimetric detection in 3802 patients from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF). Associations between free thiol concentrations and clinical characteristics and outcomes, including all-cause mortality, cardiovascular mortality, and a composite of HF hospitalization and all-cause mortality during a 2-years follow-up, were reported.

Results: Lower serum-free thiol concentrations were associated with more advanced HF, as indicated by worse NYHA class, higher plasma NT-proBNP (P < 0.001 for both) and with higher rates of all-cause mortality (hazard ratio (HR) per standard deviation (SD) decrease in free thiols: 1.253, 95% confidence interval (CI): 1.171-1.341, P < 0.001), cardiovascular mortality (HR per SD: 1.182, 95% CI: 1.086-1.288, P < 0.001), and the composite outcome (HR per SD: 1.058, 95% CI: 1.001-1.118, P = 0.046).

Conclusions: In patients with new-onset or worsening HF, a lower serum-free thiol concentration, indicative of higher oxidative stress, is associated with increased HF severity and poorer prognosis. Our results do not prove causality, but our findings may be used as rationale for future (mechanistic) studies on serum-free thiol modulation in heart failure. Associations of serum-free thiol concentrations with heart failure severity and outcomes.

Keywords: Heart failure; Oxidative stress; Redox status; Sulfhydryl groups; Thiols.

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Conflict of interest statement

S.D.A. reports receiving fees from Abbott, Actimed, Bayer, Boehringer Ingelheim, Cardiac Dimension, Cordio, Impulse Dynamics, Novartis, Occlutech, Servier, and Vifor Pharma, and grant support from Abbott and Vifor Pharma. The other authors declare that there is no relevant conflict of interest.

Figures

Fig. 1
Fig. 1
Cumulative incidence curves for the composite endpoint of all-cause mortality or heart failure-related hospitalizations at 2 years (A) and all-cause mortality at 2 years (B)
Fig. 2
Fig. 2
Forest plot depicting Hazard ratio’s for the composite endpoint of all-cause mortality or heart failure-related hospitalization (upper panel) and all-cause mortality alone (lower panel) during a 2-year follow-up, per SD decrease in serum-free thiols, across pre-specified subgroups. All Cox proportional hazards models were adjusted for the corresponding BIOSTAT-CHF risk model. Abbreviations: CKD chronic kidney disease, HF heart failure, HFmrEF heart failure with mildly reduced ejection fraction, HFpEF heart failure with preserved ejection fraction, HFrEF heart failure with reduced ejection fraction, NYHA New York Heart Association, SD standard deviation
See this image and copyright information in PMC

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