Increased plasma neopterin levels are associated with reduced endothelial function and arterial elasticity in hypertension

Inflammation has been shown to play a pivotal role in the pathogenesis and development of hypertensive vascular injury. Neopterin is a novel marker of immune activation produced mainly by activated macrophages. Few data are available to show the association between neopterin and vascular function in hypertension. The present study was designed to investigate the relationship between neopterin levels related to arterial stiffness and endothelial function in patients with hypertension, and their changes after blood pressure-lowering treatment. Twenty-four hypertensive patients and 30 age- and gender-matched healthy volunteers were recruited. Plasma neopterin levels were higher in hypertensive patients compared with their counterparts (log-neopterin: 0.77 +/- 0.18 versus 0.61 +/- 0.16, P = 0.003). Increased neopterin levels were correlated with increased brachial-ankle pulse wave velocity (baPWV; control: r = 0.659, P < 0.001; hypertension: r = 0.487, P = 0.021), and inversely associated with impaired brachial flow-mediated dilation (FMD; control: r = -0.735, P < 0.001; hypertension: r = -0.557, P = 0.005). Fifteen hypertensives received 3 months of standard antihypertensive treatment. Three months later, their plasma neopterin levels decreased (log-neopterin: 0.63 +/- 0.17 versus 0.50 +/- 0.19, P = 0.001), whereas arterial elasticity (baPWV: 1764 +/- 101 versus 1685 +/- 96 cm s(-1), P = 0.272) and endothelial function (FMD: 5.92 +/- 1.43% versus 7.73 +/- 1.31%, P < 0.05) were improved. The decline in neopterin levels was linearly correlated with baPWV decrease (r = 0.800, P < 0.001), FMD improvement (r = 0.670, P = 0.006) and blood pressure reduction (r = 0.548, P = 0.042). Our present study demonstrated for the first time that neopterin is closely correlated with vascular dysfunctions, and measurement of plasma neopterin levels might be used as a surrogate biomarker for the clinical evaluation of vascular damage and risk stratification of future atherosclerotic cardiovascular disease in patients with hypertension.