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Serum free thiols in chronic heart failure

Serum free thiols in chronic heart failure
Serum free thiols in chronic heart failure
Oxidative stress is a key element of the pathophysiology of heart failure (HF). As free thiols are readily oxidized by reactive oxygen and sulfur species, their circulating level may directly reflect the systemic redox status. This study addresses the role of serum free thiols in chronic HF, which is of particular interest as free thiols are amenable to therapeutic modulation and thus are a potential target for therapy.

Free thiols were measured in serum of 101 previously characterized stable chronic HF patients (93% male, age 63.7 ± 10.0 y, left ventricular ejection fraction 34.6 ± 8.2%), adjusted for total serum protein, and subsequently analysed for associations with clinical and outcome parameters.

The mean serum free thiol concentration was 3.6 ± 0.5 ?M/g protein. Patients with above-average levels were younger, had better renal function, lower levels of NT-proBNP and PTH, and higher levels of cholesterol. Furthermore, above-average levels were associated with favourable disease outcome, i.e. a decreased rehospitalisation rate and increased patient survival (HR 0.27 (95% CI 0.11–0.62), P = 0.002) independent of associated clinical parameters, age and PTH. After adjustment for cholesterol or established prognostic factors in HF, eGFR and NT-proBNP the association was no longer significant, suggesting involvement of these variables in a common pathophysiological pathway.

This exploratory study demonstrates favourable associations of serum free thiols with markers of HF severity and prognosis as well as disease outcome, which should be further investigated in larger prospective studies. Restoring redox status by therapeutic modulation of free thiols may be a promising strategy to improve disease outcome in CHF.
chronic heart failure, thiols, redox status, oxidative stress, rehospitalisation, survival
1043-6618
452-458
Koning, Anne M.
32547673-9cb9-4582-b2a3-51276502240b
Meijers, Wouter C.
bb88827a-4cae-426f-a8fe-fa28c99a3dee
Pasch, Andreas
5f5d9b34-4d9e-40a4-9326-fa1cd352717d
Leuvenink, Henri G.D.
0dceaec6-67e9-484c-ace9-ee86f69799d8
Frenay, Anne-Roos S.
314506f7-a54f-4950-88fa-d22db328ab1d
Dekker, Marinda M.
899acb07-e838-4948-b9f7-1c20c839e601
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
de Boer, Rudolf A.
73b3cb5d-932c-4c7f-a546-939b964e20ab
van Goor, Harry
6e4f96a5-c749-43b6-a488-6af71f932dc3
Koning, Anne M.
32547673-9cb9-4582-b2a3-51276502240b
Meijers, Wouter C.
bb88827a-4cae-426f-a8fe-fa28c99a3dee
Pasch, Andreas
5f5d9b34-4d9e-40a4-9326-fa1cd352717d
Leuvenink, Henri G.D.
0dceaec6-67e9-484c-ace9-ee86f69799d8
Frenay, Anne-Roos S.
314506f7-a54f-4950-88fa-d22db328ab1d
Dekker, Marinda M.
899acb07-e838-4948-b9f7-1c20c839e601
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
de Boer, Rudolf A.
73b3cb5d-932c-4c7f-a546-939b964e20ab
van Goor, Harry
6e4f96a5-c749-43b6-a488-6af71f932dc3

Koning, Anne M., Meijers, Wouter C., Pasch, Andreas, Leuvenink, Henri G.D., Frenay, Anne-Roos S., Dekker, Marinda M., Feelisch, Martin, de Boer, Rudolf A. and van Goor, Harry (2016) Serum free thiols in chronic heart failure. Pharmacological Research, 111, 452-458. (doi:10.1016/j.phrs.2016.06.027). (PMID:27378569)

Record type: Article

Abstract

Oxidative stress is a key element of the pathophysiology of heart failure (HF). As free thiols are readily oxidized by reactive oxygen and sulfur species, their circulating level may directly reflect the systemic redox status. This study addresses the role of serum free thiols in chronic HF, which is of particular interest as free thiols are amenable to therapeutic modulation and thus are a potential target for therapy.

Free thiols were measured in serum of 101 previously characterized stable chronic HF patients (93% male, age 63.7 ± 10.0 y, left ventricular ejection fraction 34.6 ± 8.2%), adjusted for total serum protein, and subsequently analysed for associations with clinical and outcome parameters.

The mean serum free thiol concentration was 3.6 ± 0.5 ?M/g protein. Patients with above-average levels were younger, had better renal function, lower levels of NT-proBNP and PTH, and higher levels of cholesterol. Furthermore, above-average levels were associated with favourable disease outcome, i.e. a decreased rehospitalisation rate and increased patient survival (HR 0.27 (95% CI 0.11–0.62), P = 0.002) independent of associated clinical parameters, age and PTH. After adjustment for cholesterol or established prognostic factors in HF, eGFR and NT-proBNP the association was no longer significant, suggesting involvement of these variables in a common pathophysiological pathway.

This exploratory study demonstrates favourable associations of serum free thiols with markers of HF severity and prognosis as well as disease outcome, which should be further investigated in larger prospective studies. Restoring redox status by therapeutic modulation of free thiols may be a promising strategy to improve disease outcome in CHF.

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2016 Koning-Pharmacol Res-accepted.pdf - Accepted Manuscript
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Accepted/In Press date: 30 June 2016
e-pub ahead of print date: 1 July 2016
Published date: September 2016
Keywords: chronic heart failure, thiols, redox status, oxidative stress, rehospitalisation, survival
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 399208
URI: https://eprints.soton.ac.uk/id/eprint/399208
ISSN: 1043-6618
PURE UUID: 3022e434-a7eb-4204-8752-7234a956535e
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 09 Aug 2016 11:51
Last modified: 10 Dec 2019 06:27

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Contributors

Author: Anne M. Koning
Author: Wouter C. Meijers
Author: Andreas Pasch
Author: Henri G.D. Leuvenink
Author: Anne-Roos S. Frenay
Author: Marinda M. Dekker
Author: Martin Feelisch ORCID iD
Author: Rudolf A. de Boer
Author: Harry van Goor

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