日本东部系统性硬化症相关肺动脉高压队列研究（HAPPINESS研究）：一项观察性研究的方案和基线数据

A cohort study in HigAshi-nippon of Pulmonary hyPertensIoN in systEmic SclerosiS (HAPPINESS study): protocol and baseline data for an observational study.

作者信息

Takeyama Shuhei, Hanaoka Hironari, Hashimoto Akiyoshi, Ishii Yusho, Shimizu Yuka, Takeuchi Toshiharu, Shimoyama Shuhei, Kuwana Masataka, Higuchi Tomoaki, Yoshimura Masaru, Kataoka Hiroshi, Shirota Yuko, Okada Kazufumi, Ito Yoichi M, Hisada Ryo, Kamada Kazuro, Ishigaki Sho, Horita Tetsuya, Atsumi Tatsuya, Kato Masaru

机构信息

Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

出版信息

BMC Rheumatol. 2025 Feb 26;9(1):25. doi: 10.1186/s41927-025-00474-2.

DOI:10.1186/s41927-025-00474-2

PMID:40012072

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11863849/

Abstract

BACKGROUND

Pulmonary hypertension (PH) is the leading cause of death among patients with systemic sclerosis (SSc). Recently, early therapeutic intervention to improve the prognosis was suggested, and the definition of PH was recently revised by lowering the cut-off value of mean pulmonary arterial pressure (mPAP) from ≥ 25 to > 20 mmHg. However, the optimal threshold for therapeutic intervention remains unclear. We aim to evaluate the prognosis of patients with SSc and its relationship with mPAP.

METHODS

For this non-interventional retrospective and prospective cohort study, we enrolled patients with SSc or scleroderma spectrum disorders accompanied by other connective tissue diseases who underwent right heart catheterization (RHC) for suspected PH from 2010 to 2023. The date of the first RHC was defined as the baseline. Enrolled patients were classified into three groups based on their mPAP at the first RHC (≤ 20, 21-24, and ≥ 25 mmHg) and are being observed from baseline up to three years. The primary endpoint is the time between the first RHC and the first hospitalisation or death due to worsening PH.

RESULTS

This study was approved by the Ethics Committee of Hokkaido University Hospital. A total of 229 patients were enrolled from 12 participating centres, with 41 prospectively followed up and 188 retrospectively followed up. The number of patients in each group (an mPAP of ≤ 20, 21-24, and ≥ 25 mmHg) is 79, 26, and 124, respectively. The observation is expected to be completed by December 2026. Findings will be disseminated at scientific conferences, peer-reviewed journals.

CONCLUSIONS

The findings of this study that we will obtain are expected to provide important information that will lead to improvements in the diagnosis of PH and the prognosis of patients.

TRIAL REGISTRATION

This study was approved by the Ethics Committee of Hokkaido University Hospital (approval number 022-0109). It has been registered in the Japan Registry of Clinical Trials as jRCT1010220025 since November 7, 2022.

摘要

背景

肺动脉高压（PH）是系统性硬化症（SSc）患者的主要死因。最近，有人提出进行早期治疗干预以改善预后，并且最近对PH的定义进行了修订，将平均肺动脉压（mPAP）的临界值从≥25 mmHg降低至>20 mmHg。然而，治疗干预的最佳阈值仍不清楚。我们旨在评估SSc患者的预后及其与mPAP的关系。

方法

对于这项非干预性回顾性和前瞻性队列研究，我们纳入了2010年至2023年因疑似PH接受右心导管检查（RHC）的SSc或硬皮病谱系障碍并伴有其他结缔组织疾病的患者。首次RHC的日期定义为基线。根据首次RHC时的mPAP将纳入的患者分为三组（≤20、21 - 24和≥25 mmHg），并从基线开始观察长达三年。主要终点是首次RHC与因PH恶化导致的首次住院或死亡之间的时间。

结果

本研究已获得北海道大学医院伦理委员会的批准。共有229名患者从12个参与中心入组，其中41名进行前瞻性随访，188名进行回顾性随访。每组患者数量（mPAP≤20、21 - 24和≥25 mmHg）分别为79、26和124名。预计观察将于2026年12月完成。研究结果将在科学会议、同行评审期刊上发表。