Impaired endothelium-dependent and endothelium-independent systemic vasodilatory reserve in pulmonary hypertension regardless the clinical group: A generalized dysfunction beyond the pulmonary arteries?

Abstract

Endothelium-dependent (ED) and endothelium-independent (EI) flow-mediated vasodilatation (FMD) have been used as measures of systemic arterial vasodilatory reserve. In this study, we aimed to assess both ED-FMD and EI-FMD in different groups with pulmonary hypertension (PH), and to investigate the relationship of these measures with clinical, echocardiographic, and invasive parameters of diseases severity and targeted treatment status. Our study population comprised 41 patients with PH [28 (68.2%) women, age 46.3±19.6 years] including idiopathic pulmonary arterial hypertension, Eisenmenger syndrome, and chronic thromboembolic PH in whom diagnosis were confirmed in accordance with current guidelines and 17 age and sex-matched healthy controls. The brachial artery (BA) was used for assessment of FMD with Duplex ultrasound, and serial changes in diameter were recorded at baseline, 1, and 3 minutes after termination of 2-minute external occlusive compression for ED-FMD, and after sublingual intake of glycerol trinitrate for EI-FMD, respectively. Compared with controls, overall the PH group showed significantly lower ED-FMD (0.65±0.21 vs. 0.30±0.23 and 0.65±0.18 vs. 0.24±0.21) and EI-FMD (0.67±0.15 vs. 0.37±0.25 and 0.75±0.20 vs. 0.32±0.24) responses at 1st and 3rd min (p<0.001 for all). All these changes in the values of ED-FMD and EI-FMD were comparable among the PH subgroups. Neither ED-FMD nor EI-FMD were correlated with measures of PH severity and targeted therapy (TT) status (p>0.05). Our results suggest an impaired BA vasodilatory reserve in patients with PH regardless of the clinical subgroup. Although these findings seem to be consistent with systemic dysfunction, acute FMD may not reflect the severity of PH and cannot be used as a potential surrogate for outcome in this setting.