Abstract
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.
Highlights
Serum free thiols (R-SH, sulfhydryl groups) reliably reflect systemic oxidative stress
Abdulle et al BMC Medicine (2020) 18:130 (Continued from previous page). In this large population-based cohort study, serum free thiols significantly predicted the risk of CV events and all-cause mortality
A history of cardiovascular disease was observed in 3.6% of the total cohort, and diabetes was found in 2.4% of the total number of participants
Summary
Serum free thiols (R-SH, sulfhydryl groups) reliably reflect systemic oxidative stress. These latter strategies have faced multiple problems, including limited availability of non-invasive predictive biomarkers to assess the risk of cardiovascular (CV) events or mortality. Overproduction of ROS, as reflected by reduced levels of free thiols, is frequently observed in human disease (like in chronic kidney disease, chronic heart failure, diabetes, cancer, systemic sclerosis, and Crohn’s disease) that is typically associated with oxidative stress [7,8,9,10]. Studies from our center have demonstrated that higher levels of serum free thiols (i.e., lower levels of oxidative stress) are associated with favorable outcomes in patients with chronic heart failure [7], as well as with a beneficial outcome and cardiovascular risk profile in renal transplant recipients [11]
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