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Published on: July 3, 2013
Citrulline and long-term mortality in patients with cardiovascular disease
Radosław Andrzej Konieczny1, Ewa Żurawska-Płaksej2, Konrad Kaaz3
1Jan Mikulicz-Radecki University Teaching Hospital, Clinic of Gastroenterology and Hepatology, Wrocław, Poland.
Insights
Low citrulline levels, a marker of intestinal damage, do not predict long-term mortality in cardiovascular disease (CVD) patients. Citrulline levels also showed no association with trimethylamine N-oxide (TMAO) levels in this cohort.
Area of Science:
- Cardiology
- Gastroenterology
- Metabolomics
Background:
- Cardiovascular disease (CVD) is linked to intestinal barrier dysfunction and increased gut permeability.
- Elevated intestinal permeability allows microbial metabolites, like trimethylamine N-oxide (TMAO), to potentially accelerate CVD progression.
- Citrulline, a marker of enterocyte mass, can indicate intestinal epithelial damage, but its prognostic role in CVD and relation to TMAO is unclear.
Purpose of the Study:
- To investigate the association between citrulline levels and long-term mortality in patients with CVD.
- To explore the relationship between serum citrulline and TMAO concentrations in CVD patients.
- To assess citrulline as a marker of intestinal barrier disruption in the context of CVD outcomes.
Main Methods:
- Retrospective analysis of serum citrulline levels in 1036 hospitalized CVD patients (2013-2015).
- Evaluation of associations between citrulline levels and 5-year mortality, anthropometric, and biochemical parameters.
- Assessment of correlations between serum citrulline and TMAO levels, including subgroup analyses for acute coronary syndrome, chronic coronary syndrome, chronic heart failure, and atrial fibrillation.
Main Results:
- Serum citrulline levels were not significantly associated with 5-year mortality in the overall CVD patient group (HR=0.99, p=0.49).
- A significant difference in median citrulline levels was observed between deceased and surviving patients with acute coronary syndrome (p=0.025).
- No significant correlation was found between serum citrulline and TMAO levels (Kendall's tau=0.027).
Conclusions:
- Reduced citrulline levels do not serve as a predictor for long-term mortality in hospitalized cardiovascular disease patients.
- Serum citrulline levels are not associated with TMAO concentrations in patients with CVD.
- The study suggests that citrulline's role as a prognostic marker for long-term mortality in CVD may be limited, despite its association with intestinal health.
Background:
Cardiovascular disease (CVD) is associated with intestinal barrier dysfunction and increased intestinal permeability. Increased intestinal permeability to gut microbial metabolites may accelerate the progression of CVD. Plasma citrulline levels are a marker of functional enterocyte mass, and reduced citrulline levels indicate intestinal epithelial damage. Citrulline was reported as a useful prognostic marker in critically ill patients. However, data are lacking on the association of citrulline with long-term mortality in patients with CVD and with the levels of trimethylamine N-oxide (TMAO), a microbiota-derived metabolite which has been implicated in the pathogenesis of CVD.
Objectives:
To assess the effect of citrulline levels, a marker of intestinal barrier disruption, on long-term mortality in patients with CVD. Moreover, the relationship between the concentrations of 2 biomarkers - citrulline and TMAO - was assessed.
Material And Methods:
Serum citrulline levels were retrospectively assessed in 1036 consecutive patients with CVD (median age: 62 years; 61% men) hospitalized between 2013 and 2015. Associations of citrulline levels with 5-year mortality rates as well as anthropometric and biochemical parameters were evaluated for the entire study group and in subgroups of patients with acute coronary syndrome (ACS), chronic coronary syndrome, chronic heart failure (chronic HF), and atrial fibrillation (AF). Correlations between serum citrulline and TMAO levels were assessed.
Results:
The median citrulline level in the study population was 22.5 μM (interquartile range (IQR): 17.8-27.9). Citrulline levels were not associated with 5-year mortality in patients with CVD (hazard ratio (HR) = 0.99; 95% confidence interval (95% CI): 0.97-1.00; p = 0.49). Median citrulline levels differed significantly between deceased patients and survivors at 5 years in patients with ACS (p = 0.025). There were no significant correlations between citrulline and TMAO levels (Kendall's tau = 0.027).
Conclusions:
Decreasing citrulline levels do not predict long-term mortality of hospitalized patients with CVD. Moreover, they are not associated with the serum levels of TMAO in these patients.
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