A Natural History Study of Novel Biomarkers in Pulmonary Arterial Hypertension

PAH（即1组PAH）是一种罕见的疾病，与较差的生存率相关。由于1)遗传易感性和2)引发肺血管损伤的触发刺激导致的内皮功能障碍，双重打击假说似乎在PAH的发病和进展中都起着核心作用。炎症似乎驱动这种功能失调的内皮表型，在遗传易感的特发性PAH （IPAH）患者和疾病相关PAH患者中传播损伤和修复周期。然而，尽管越来越多的证据表明PAH患者存在血管炎症，但缺乏详细的表型研究来研究这一过程的时间演变及其对右心室（RV）和肺血管重构的贡献。

PAH (i.e. Group 1 PAH) is a rare disorder associated with poor survival. Endothelial dysfunction resulting from 1) genetic susceptibility, and 2) a triggering stimulus that initiates pulmonary vascular injury, the two-hit hypothesis, appears to play a central role both in the pathogenesis and progression of PAH. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic PAH (IPAH) and patients with disease-associated PAH. However, despite mounting evidence of vascular inflammation in patients with PAH, detailed phenotypic studies are lacking on the temporal evolution of this process and its contribution to right ventricular (RV) and pulmonary vascular remodeling. The protocol was initially approved by the NHLBI IRB in October 2012. Subsequently IRB approval was sought and obtained at collaborating sites and various amendments were brought into alignment at all institutions by summer 2013. Referrals are being received from multiple sites. To date 51 subjects have been screened for this study and 14 have been enrolled. We hypothesize that a detailed characterization of the temporal evolution of vascular inflammation and neurohormonal activation in PAH and its impact on RV and pulmonary vascular function will add prognostic value to traditional measures of disease severity and suggest novel therapeutic targets for future research.