Prognostic Factors, Genetics, and Therapy in PAH-SSD

描述（由申请方提供）：在包括肺动脉高压的疾病组中，硬皮病相关PAH（PAH-SSD）与高死亡率相关，目前对该疾病患者的治疗有限。尽管与特发性PAH（IPAH）的临床和组织学相似，但在拟定的发病机制、治疗反应和生存率方面存在明显差异。例如，这两种疾病的典型肺血管丛状病变的起源可能不同。此外，尽管IP AH和PAH-SSD患者均对前列环素治疗有反应，但IP AH患者的反应程度更深。最终，PAH-SSD患者的生存率比IP AH患者差得多。利用约翰霍普金斯肺动脉高压登记研究中的大量患者，我们计划前瞻性研究PAH患者，具体目的如下：1）确定与IPAH患者相比，PAH-SSD患者疾病进展和存活的预后因素，2）通过疾病特异性cDNA微阵列分析鉴定PAH-SSD中的候选基因，和3）评价辛伐他汀治疗对PAH患者临床结局的影响，通过运动能力、博格呼吸困难评分、WHO/NYHA心功能分级、SF-36调查评估的生活质量和至临床恶化的时间进行评估。

DESCRIPTION (provided by applicant): Within the group of disorders that comprise pulmonary arterial hypertension, PAH related to scleroderma (PAH-SSD) is associated with a high mortality and current therapy for patients with this disease is limited. Despite clinical and histologic similarities to idiopathic PAH (IPAH), distinct differences exist in proposed pathogenesis, response to therapy, and survival. For instance, the origin of the classic plexiform lesion in the pulmonary vasculature may differ between these two entities. Further, although both patients with IP AH and PAH-SSD respond to epoprostenoid therapy, the magnitude of response is more profound for patients with IP AH. Ultimately, survival for patients with PAH-SSD is much poorer than for patients with IP AH. Utilizing the large number of patients in our pulmonary hypertension registry at Johns Hopkins, we propose to prospectively study patients with PAH with the following specific aims: 1) to define prognostic factors for disease progression and survival in patients with PAH-SSD compared to patients with IP AH, 2) to identify candidate genes in PAH-SSD by disease-specific cDNA microarray analyses, and 3) to evaluate the effect of simvastatin therapy on clinical outcomes as assessed by exercise capacity, Borg dyspnea score, WHO/NYHA functional class, quality of life assessed by SF-36 survey, and time to clinical worsening in patients with PAH.