Abstract 2543: Plasma Biopterins are Independent Predictors of Arterial Distensibility and Endothelial Function in Coronary Artery Disease -A Cardiovascular MR study.
Background Plasma tetrahydrobiopterin (BH4) is an essential cofactor of endothelial nitric oxide synthase (eNOS) function in human vasculature. BH4 is oxidised to dihydrobiopterin (BH2) and biopterin (B), a process that is accelerated in coronary artery disease (CAD). In addition, the synthesis of biopterins is upregulated in proinflammatory states. We examined the importance of plasma biopterin levels in relation to arterial stiffness and endothelial function, both independent predictors of vascular outcome, in patients with advanced atherosclerosis.
Methods Changes in aortic distensibility and brachial artery flow-mediated dilatation (FMD) were quantified by high-resolution cine MRI (1.5 Tesla) in 56 patients with CAD. To search for predictors of arterial stiffness and endothelial function, we performed multivariate analysis using plasma biopterins and classical risk factors for CAD (smoking, gender, body mass index, diabetes, hypertension, hypercholesterolemia) as independent variables in each regression model.
Results Plasma BH4 concentration was negatively correlated with aortic distensibility (r=-0.446, p=0.004). A similar finding was also observed for total biopterins (BH4, BH2 and B; r=0.393, p=0.012). In addition the concentration of plasma BH2, a product of BH4 oxidation, was negatively correlated with FMD (r=-0.445, p=0.007), while there was a borderline non-significant association between total biopterins and FMD (r=-0.248, p=0.1) In multivariate linear regression, plasma BH4 concentration was the only independent predictor of aortic distensibility (B(SEM): - 4.1 x 10-5 (1.33 x 10-5), p=0.0001) and stiffness index (B(SEM): 0.063 (0.014), p=0.0001). Similarly, the only independent predictors for FMD were plasma BH2 concentration (B(SEM): -0.50 (0.183), p=0.01) and smoking ((B(SEM): -2.22 (0.95), p=0.027).
Conclusions This is the first study to demonstrate that in patients with advanced atherosclerosis, plasma biopterins are independently associated with reduced vascular distensibility, while BH2, an index of BH4 oxidation, is associated with impaired endothelial function. The measurement of plasma biopterins may a useful additional biomarker in the assessment of patients with coronary artery disease.