Division of Vascular Medicine, Department of Internal Medicine, University of Groningen - University Medical Center Groningen, Groningen, the Netherlands.
Department of Gastroenterology and Hepatology, University of Groningen - University Medical Center Groningen, Groningen, the Netherlands.
BMC Med. 2020 May 27;18(1):130. doi: 10.1186/s12916-020-01587-w.
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.
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.
The 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.
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.
血清游离巯基（R-SH，巯基）可靠地反映全身氧化应激。由于血清游离巯基易被活性物质氧化，全身氧化应激通常与血清游离巯基水平降低有关。游离巯基与许多患者群体的有利疾病结局相关，目前的假设是氧化应激也可能在心血管疾病中发挥重要作用。在这项研究中，我们旨在通过研究其与心血管（CV）事件和全因死亡率的风险关系，在普通人群中确定血清游离巯基的作用。
纳入来自普通人群的预防肾脏和血管终末期疾病（PREVEND）队列研究的参与者（n=5955）。在基线时，定量测定游离巯基的血清水平，并根据总蛋白水平进行调整。研究了蛋白校正后的血清游离巯基水平与临床和生化参数的关系，以及与 CV 事件和全因死亡率的风险的关系。
平均蛋白校正的血清游离巯基水平为 5.05±1.02μmol/g 蛋白。即使在调整潜在混杂因素后，蛋白校正后的血清游离巯基仍显著预测 CV 事件的风险（每加倍风险比[HR]0.68[95%置信区间[CI]0.47-1.00]，P=0.048）。同样，蛋白校正后的血清游离巯基也显著预测全因死亡率的风险（每加倍 HR 0.66[95%CI 0.44-1.00]，P=0.050）。分层分析显示，较低的 BMI、无高血压和无糖尿病的受试者的 HR 较低，而白蛋白尿的受试者的 HR 较低。
在这项大型基于人群的队列研究中，血清游离巯基显著预测 CV 事件和全因死亡率的风险。我们的结果强调了血清游离巯基的潜在重要性和临床适用性，因为它们可以进行治疗干预。
