• Amaal E Abdulle, Arno R Bourgonje, Lyanne M Kieneker, Anne M Koning, S la Bastide-van Gemert, Bulthuis Marian L C MLC Department of Pathology and Medical Biology, Section Pathology, University of Groningen - University Medical Center Groningen, Groningen, the Neth, Gerard Dijkstra, Klaas Nico Faber, Dullaart Robin P F RPF Division of Endocrinology, Department of Internal Medicine, University of Groningen - University Medical Center Groningen, Groningen, the Netherlan, Bakker Stephan J L SJL Division of Nephrology, Department of Internal Medicine, University of Groningen - University Medical Center Groningen, Groningen, the Netherlands., Gans Reinold O B ROB Division of Vascular Medicine, Department of Internal Medicine, University of Groningen - University Medical Center Groningen, Groningen, the Netherl, Ron T Gansevoort, Douwe J Mulder, Andreas Pasch, and Harry van Goor.
• Division of Vascular Medicine, Department of Internal Medicine, University of Groningen - University Medical Center Groningen, Groningen, the Netherlands.
• Bmc Med. 2020 May 27; 18 (1): 130.

BackgroundSerum free thiols (R-SH, sulfhydryl groups) reliably reflect systemic oxidative stress. Since serum free thiols are rapidly oxidized by reactive species, systemic oxidative stress is generally associated with reduced serum free thiol levels. Free thiols associate with favorable disease outcomes in many patient cohorts, and the current hypothesis is that oxidative stress might also play an important role in cardiovascular disease. In this study, we aimed to establish the role of serum free thiols in the general population by investigating their relationship with the risk of cardiovascular (CV) events and all-cause mortality.MethodsParticipants (n = 5955) of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort study from the general population were included. At baseline, serum levels of free thiols were quantified and adjusted to total protein levels. Protein-adjusted serum free thiol levels were studied for their associations with clinical and biochemical parameters, as well as with the risk of CV events and all-cause mortality.ResultsThe mean protein-adjusted serum free thiol level was 5.05 ± 1.02 μmol/g of protein. Protein-adjusted serum free thiols significantly predicted the risk of CV events, even after adjustment for potential confounding factors (hazard ratio [HR] per doubling 0.68 [95% confidence interval [CI] 0.47-1.00], P = 0.048). Similarly, protein-adjusted serum free thiols were significantly predictive of the risk of all-cause mortality (HR per doubling 0.66 [95% CI 0.44-1.00], P = 0.050). Stratified analyses revealed lower HRs for subjects with a lower body mass index (BMI), without hypertension, and without diabetes. Conversely, HRs were lower in subjects with albuminuria.ConclusionsIn this large population-based cohort study, serum free thiols significantly predicted the risk of CV events and all-cause mortality. Our results highlight the potential significance and clinical applicability of serum free thiols since they are amendable to therapeutic intervention.

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