Prognostic Factors, Genetics, and Therapy in PAH-SSD

描述（由申请人提供）：在包括肺动脉高压的疾病组中，与硬皮病相关的PAH （PAH- ssd）与高死亡率相关，目前对该疾病患者的治疗有限。尽管临床和组织学上与特发性PAH （IPAH）相似，但在发病机制、治疗反应和生存方面存在明显差异。例如，典型的肺血管丛状病变的起源可能在这两种实体之间有所不同。此外，尽管ipah和PAH-SSD患者都对类epoprostenoid治疗有反应，但ipah患者的反应幅度更大。最终，PAH-SSD患者的生存率远低于IP AH患者。利用约翰霍普金斯大学肺动脉高压登记处的大量患者，我们建议对PAH患者进行前瞻性研究，具体目的如下：1)确定PAH- ssd患者与IP AH患者相比疾病进展和生存的预后因素；2)通过疾病特异性cDNA微阵列分析确定PAH- ssd的候选基因；3)评估辛伐他汀治疗对PAH患者运动能力、Borg呼吸困难评分、WHO/NYHA功能分级、SF-36调查评估的生活质量以及临床恶化时间等临床结果的影响。

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.