Small artery dilation and endothelial markers in cardiovascular risk patients

Abstract

The use of methods based on reactive hyperaemia of small distal arteries to assess endothelial function (EF) is increasing; however, the mechanisms regulating vascular function in large and small arteries are probably different. We studied the correlations between the hyperaemia reactivity of small peripheral arteries determined by peripheral artery tonometry (PAT) and the levels of serum biomarkers of EF, inflammation and oxidation in patients with cardiovascular (CV) risk factors. Four hundred and seven patients with intermediate CV risk were recruited into a cross-sectional study to examine whether soluble endothelial, inflammatory and lipid oxidative biomarkers correlate with small artery reactive hyperaemia index (saRHI) values, which were measured by PAT. A significant correlation was found between saRHI values and the concentrations of soluble E-selectin (sE-selectin) and soluble vascular cell adhesion molecule 1 (sVCAM-1). These correlations were stronger when only non-metabolic syndrome patients (46%) were analysed (r = -0·310, P < 0·0001; r = -0·264, P < 0·0001, respectively). In this subgroup, the oxidised low-density lipoprotein/LDL (oxLDL/LDL) was also correlated with saRHI (r = -0·193, P = 0·009). A stepwise regression study showed that sE-selectin was the only biomarker significantly correlated with saRHI values (P < 0·0001). In multivariate linear regression analysis, this relationship was still strong when the main confounding covariates were taken into consideration. Elevated levels of sE-selectin and, to a smaller degree, sVCAM-1 and oxLDL/LDL are associated with lower postischemic reactivity in the small distal arteries. sE-selectin is the main determinant biomarker of saRHI as assessed by regression analysis. The presence of multiple risk factors weakens this association.