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Serum free thiols predict cardiovascular events and all-cause mortality in the general population: a prospective cohort study.

ABSTRACT: BACKGROUND:Serum 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. METHODS:Participants (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. RESULTS:The mean protein-adjusted serum free thiol level was 5.05?±?1.02??mol/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. CONCLUSIONS:In 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.

SUBMITTER: Abdulle AE

PROVIDER: S-EPMC7251849 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Serum free thiols predict cardiovascular events and all-cause mortality in the general population: a prospective cohort study.

Abdulle Amaal E AE Bourgonje Arno R AR Kieneker Lyanne M LM Koning Anne M AM la Bastide-van Gemert S S Bulthuis Marian L C MLC Dijkstra Gerard G Faber Klaas Nico KN Dullaart Robin P F RPF Bakker Stephan J L SJL Gans Reinold O B ROB Gansevoort Ron T RT Mulder Douwe J DJ Pasch Andreas A van Goor Harry H

BMC medicine 20200527 1

<h4>Background</h4>Serum 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 o ...[more]

PMID: 32456645

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Project description:Introduction: Several lines of evidence reveal that cardiovascular disease (CVD) and cancer share similar common pathological milieus. The prevalence of the two diseases is growing as the population ages and the burden of shared risk factors increases. In this respect, we hypothesise that tumour biomarkers can be potential predictors of CVD outcomes in the general population. Methods: We measured six tumour biomarkers (AFP, CA125, CA15-3, CA19-9, CEA and CYFRA 21-1) and determined their predictive value for CVD in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. A total of 8,592 subjects were enrolled in the study. Results: The levels of CEA significantly predicted CV morbidity and mortality, with hazard ratios (HRs) of HR 1.28 (95% CI 1.08-1.53), respectively. Two biomarkers (CA15-3 and CEA) showed statistical significance in predicting all-cause mortality, with HRs 1.58 (95% CI 1.18-2.12) and HR 1.60 (95% CI 1.30-1.96), when adjusted for shared risk factors and prevalent CVD. Furthermore, biomarkers seem to be sex specific. CYFRA 21-1 presented as an independent predictor of CV morbidity and mortality in female, but not in male gender, with HR 1.82 (95% CI 1.40-2.35). When it comes to all-cause mortality, both CYFRA and CEA show statistical significance in male gender, with HR 1.64 (95% CI 1.28-3.12) and HR 1.55 (95% CI 1.18-2.02), while only CEA showed statistical significance in female gender, with HR 1.64 (95% CI 1.20-2.24). Lastly, CA15-3 and CEA strongly predicted CV mortality with HR 3.01 (95% CI 1.70-5.32) and HR 1.82 (95% CI 1.30-2.56). On another hand, CA 15-3 also presented as an independent predictor of heart failure (HF) with HR 1.67 (95% CI 1.15-2.42). Conclusion: Several tumour biomarkers demonstrated independent prognostic value for CV events and all-cause mortality in a large cohort from the general population. These findings support the notion that CVD and cancer are associated with similar pathological milieus.

Project description:BackgroundEmergency general surgery (EGS) is associated with increased mortality, with kidney failure a contributing risk, but comparative outcomes between patients with kidney failure and the general population are lacking.MethodsIn this retrospective population-cohort study, data were analysed for all EGS procedures performed in England between 1 April 2004 and 31 March 2019. EGS was defined as partial colectomy, small bowel resection, cholecystectomy, appendicectomy, lysis of peritoneal adhesions, surgery for peptic ulcer, or laparotomy. The main outcome measure was major adverse cardiovascular events (MACEs) and all-cause mortality after surgery.ResultsFrom 691 064 procedures, 0.16 per cent (n = 1097) and 0.23 per cent (n = 1567) were performed on kidney transplant and dialysis recipients respectively. Laparotomy was the most frequent EGS procedure for kidney transplant (46 per cent of procedures, n = 507) and dialysis (45 per cent of procedures, n = 704) recipients, with the highest 30-day and 1-year mortality. In logistic regression analysis, both kidney failure cohorts had higher risk for experiencing MACEs in the postoperative interval after emergency laparotomy; within 3 months (dialysis; OR 2.44 (95 per cent c.i. 2.08 to 2.87), P < 0.001 and transplant; OR 2.05 (95 per cent c.i. 1.57 to 2.68), P < 0.001) and within 1 year (dialysis; OR 2.39 (95 per cent c.i. 2.06 to 2.77), P < 0.001 and transplant; OR 2.21 (95 per cent c.i. 1.76 to 2.77), P < 0.001); however, in a propensity-score-matched cohort, increased risk for MACEs was observed among dialysis patients after emergency laparotomy (HR 2.10 (95 per cent c.i. 1.82 to 2.43), P < 0.001) but not kidney transplant recipients (HR 1.17 (95 per cent c.i. 0.97 to 1.41), P = 0.096).ConclusionMortality after emergency surgery is higher for patients with kidney failure and dialysis is worse than kidney transplantation, with cardiovascular deaths more common than the general population.

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Serum free thiols predict cardiovascular events and all-cause mortality in the general population: a prospective cohort study.

Publications

Serum free thiols predict cardiovascular events and all-cause mortality in the general population: a prospective cohort study.

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