Abstract
Objectives: Atrial fibrillation (AF) is characterized by an oxidative imbalance, which is associated with an increased risk of cardiovascular events (CVEs). It is unclear whether low grade endotoxemia may contribute to the impaired antioxidant status in AF patients. We investigated the relationship between circulating lipopolysaccharides (LPS) and antioxidant status in AF patients.Patients and Methods: Post-hoc analysis from the ongoing prospective observational cohort ATHERO-AF study including 907 patients. Antioxidant status was evaluated by the activity of glutathione peroxidase 3 (GPx3) and superoxide dismutase (SOD). Patients were divided into two groups to evaluate the risk of CVEs: (1) LPS below median and GPx3 above median (n = 254); (2) LPS above median and GPx3 below median (n = 263).Results: The mean age was 73.5 ± 8.3 years, and 43.1% were women. Median LPS and GPx3 were 50.0 pg/ml [interquartile range (IQR) 15–108] and 20.0 U/ml (IQR 10.0–34.0), respectively. Patients of Groups 2 were older, with a higher prevalence of heart failure. LPS above the median was associated with reduced GPx3 [Odds Ratio for LPS 1.752, 95% Confidence Interval (CI) 1.344–2.285, p < 0.001] and SOD (OR 0.525, 95%CI 0.403–0.683) activity after adjustment for CHA2DS2VASc score. In a mean follow-up of 54.0 ± 36.8 months, 118 CVEs occurred, 42 in Group 1 and 76 in Group 2 (Log-Rank test p = 0.001). At multivariable Cox regression analysis, Group 2 was associated with a higher risk of CVEs [Hazard Ratio (HR) 1.644, 95%CI 1.117–2,421, p = 0.012], along with age ≥ 75 years (HR 2.035, 95%CI 1.394–2.972, p < 0.001), diabetes (HR 1.927, 95%CI 1.280–2.900, p = 0.002), and previous cerebrovascular disease (HR 1.895, 95%CI 1.251–2.870, p = 0.003) and previous cardiovascular disease (HR 1.708, 95%CI 1.149–2.538, p = 0.008).Conclusions: Our study indicates that circulating LPS may contribute to impaired antioxidant status in patients with AF. Patients with coincidentally high LPS and reduced GPx3 activity showed the highest risk of CVEs.
Highlights
A clinically relevant incidence of cerebrovascular and cardiovascular complications is still detectable in patients with atrial fibrillation (AF) despite optimal anticoagulant treatment [1,2,3]
This may be due to several reasons including both a suboptimal integrated prevention strategy for the management of comorbidities [4], as shown by data indicating that only a minority of patients with AF are currently managed according to the guidelines-recommended “Atrial fibrillation Better Care” (ABC) pathway [5]
We investigated the association between circulating gut-derived LPS and the activity of the glutathione peroxidase 3 (GPx3), the blood isoform of GPx involved in the detoxification of superoxide anion, in patients with AF enrolled in the ATHERO-AF study cohort
Summary
A clinically relevant incidence of cerebrovascular and cardiovascular complications is still detectable in patients with atrial fibrillation (AF) despite optimal anticoagulant treatment [1,2,3] This may be due to several reasons including both a suboptimal integrated prevention strategy for the management of comorbidities [4], as shown by data indicating that only a minority of patients with AF are currently managed according to the guidelines-recommended “Atrial fibrillation Better Care” (ABC) pathway [5]. The presence of non-traditional risk factors which may contribute to this residual cardiovascular risk has been demonstrated, for which specific prevention strategies are not yet established In this context, oxidative stress, endotoxemia and low-grade inflammation have been the most widely investigated in patients with cardiovascular disease and in the AF population [6,7,8]. Markers of oxidative stress seem to have a prognostic role for cardiovascular events (CVEs) in AF [13]
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