第一部分 夜间长时间低氧对特发性肺动脉高压患者的影响

研究背景：睡眠呼吸障碍会导致多种心血管并发症并增加患者不良预后的风险。而目前肺动脉高压患者合并睡眠呼吸障碍的临床诊治仍存在一定争议。本研究旨在探究特发性肺动脉高压(idiopathic pulmonary arterial hypertension，IPAH)患者夜间长时间低氧的发生率，评估其对 IPAH 患者临床状态的影响，并确定可能的影响因素。研究方法：入组 2018 年 1 月至 2019 年 7 月经右心导管检查诊断为 IPAH 并接受夜间睡眠呼吸监测的患者。夜间低氧时间定义为氧饱和度保持在 90%以下的时间。夜间长时间低氧定义为夜间氧饱和度水平低于 90%的持续时间超过总记录时间的10%。收集患者基线临床特征和参数，根据有或无夜间长时间低氧将 IPAH 患者分为两组进行对比，此外，进行 Logistic 回归以确定与 IPAH 患者中与夜间长时间低氧相关的可能因素。研究结果：共纳入 50 名 IPAH 患者。其中，17 名患者出现夜间长时间低氧。夜间长时间低氧的患者与无夜间长时间低氧的患者相比，年龄更大、六分钟步行距离（6MWD）更短、平均右心房压更高、日间动脉氧分压更低，VE/VCO2和 VE/VCO2斜率差异显著(P<0.05)。多变量 Logistic 回归分析表明，校正年龄、性别和体重指数后，6 MWD (OR = 0.971, 95% CI: 0.948–0.994,P = 0.013) 和 VE/VCO2 斜率（OR =1.095, 95% CI: 1.010–1.307, P = 0.032）与夜间长时间低氧独立相关。研究结论：IPAH 患者中夜间长时间低氧较为常见。夜间长时间低氧可能会加重 IPAH 患者的临床情况。在 IPAH 患者中，6 MWD 和 VE/VCO2 斜率可以在校正年龄、性别和体重指数后提示夜间长时间低氧的发生。关键词：夜间低氧；夜间长时间低氧；特发性肺动脉高压

第二部分 肺动脉高压合并阻塞性睡眠呼吸暂停患者的临床特点

研究目的：阻塞性睡眠呼吸暂停（obstructive sleep apnea，OSA）是肺动脉高压（pulmonary hypertension，PH）的病因之一，也可作为 PH 的合并症出现。国内外既往研究显示的 PH 患者中 OSA 的患病率差异很大，且其临床诊断和治疗仍存在争议。本临床研究的目的是观察和总结 PH 患者中 OSA 的发生率和临床特征，探讨 PH合并 OSA 的潜在预测因素。研究方法：纳入 2018 年 12 月至 2020 年 12 月经右心导管诊断为 PH 且接受夜间睡眠呼吸监测的患者。OSA 定义为呼吸暂停低通气（apnea hypopnea index，AHI)指数≥5 次/时，且≥50%的呼吸暂停事件是阻塞性的。收集患者基线临床参数以比较有和无 OSA 的 PH 患者的临床特点。并进行 Logistic 回归分析以确定 PH 患者合并OSA 的危险因素。研究结果：140 名 PH 患者中共有 35 名(25%)患有OSA。OSA 在 PH 患者中相对常见，尤其是在慢性血栓栓塞性肺动脉高压患者（50%）和肺部疾病和（或）低氧相关 PH 患者（76%）中患病率较高。合并 OSA 的患者大多为男性，年龄较大，日间动脉氧分压较低。经 Logistic 回归分析发现，在 PH 患者中，年龄较大、男性和较低的日间动脉血氧分压与 OSA 相关。研究结论：OSA 在 PH 患者中较为常见。较低的日间动脉氧分压、较大年龄、男性与 OSA 相关，提示患者合并 OSA 的可能性较大，应进行睡眠呼吸监测。

关键词：肺动脉高压；阻塞性睡眠呼吸暂停；危险因素

第三部分 血清尿酸对特发性肺动脉高压患者疾病严重程度和 5 年死亡率的影响研究背景：长期以来，血清尿酸（uric acid，UA）被认为是肺动脉高压不良结局的预后因素。然而，在靶向药物治疗时代，关于特发性肺动脉高压（idiopathicpulmonary arterial hypertension，IPAH）患者中血清尿酸的预后价值的证据仍然很少。本研究旨在探讨血清 UA 水平对 IPAH 患者疾病严重程度和死亡率的影响。研究方法：连续纳入诊断为 IPAH 的患者，收集基线和首次随访时的血清 UA 水平。当女性血清 UA 水平≥357 µmol/L，男性≥420 µmol/L 时，患者被分为“高尿酸血症”组，否则为“正常尿酸血症”组。研究 UA 与右心导管插入术测定的血流动力学之间的潜在关系。通过 Kaplan-Meier 分析和 Cox 比例风险模型评估 UA 和生存率之间的关联。研究结果：207 例 IPAH 患者中，121 例（58.5%）患有高尿酸血症。较高的血清 UA 水平与较低的心脏指数(r = 0.47, P < 0.001) 和较高的肺血管阻力 (r = 0.36, P< 0.001) 相关。在 34 个月的中位随访期间，共有 32 人死亡，死亡率为 15.5%。高尿酸血症组患者的存活率明显低于尿酸正常组患者（对数秩检验，P = 0.002）。基线时的高尿酸血症与 5 年死亡风险增加 2.6 倍独立相关，这在不同亚组中也是一致的，尤其是在女性和 30 岁以上的人群中（每个亚组均满足 P<0.05）。UA 变异性较高的个体的死亡率高于 UA 稳定的个体（对数秩检验，P = 0.024）。研究结论：基线高尿酸血症和首次随访时血清 UA 的高变异性与 IPAH 患者较高的 5 年死亡率相关。密切监测 UA 水平可能有助于早期识别具有较高死亡风险的 IPAH患者。

关键词：高尿酸血症；特发性肺动脉高压；死亡率；结局；肺动脉高压；尿酸

PartI Nocturnal hypoxia in patients with idiopathic pulmonary arterial hypertension

Background: Sleep-disordered breathing (SDB) causes a variety of cardiovascular complications and increases the risk of a poor prognosis in patients. There is still some controversy regarding the clinical diagnosis and treatment of sleep-disordered breathing in patients with pulmonary hypertension (PH). The aim of this study was to determine the incidence of desaturation in idiopathic pulmonary arterial hypertension (IPAH) patients, evaluate the effect of desaturation on the clinical status of patients with IPAH, and identify possible influencing factors. Methods: Patients with IPAH diagnosed by right heart catheterization (RHC)who underwent overnight cardiorespiratory monitoring from January 2018 to July 2019 were enrolled. Nocturnal hypoxic time was defined as the time that oxygen saturation remained below 90%. Desaturation was defined as a nocturnal oxygen saturation level less than 90% for more than 10% of the total recording time. Baseline clinical characteristics and parameters were collected to compare IPAH patients with and without desaturation. In addition, logistic regression was performed to identify possible factors associated with desaturation in IPAH patients.Results: Fifty patients with IPAH were included. Among them, 17 patients presented desaturation. Patients with desaturation were older, had a shorter six-minwalking distance (6MWD), had a higher mean right atrial pressure, and had a lowerdaytime arterial oxygen partial pressure than patients without desaturation, and there were significant differences in the VE/VCO2 and VE/ VCO2 slope (P < 0.05). Themultivariate logistic regression analysis indicated that the 6 MWD (OR = 0.971, 95% CI:0.948–0.994, P = 0.013) and VE/VCO2 slope (OR = 1.095, 95% CI: 1.010–1.307, P =0.032) were independently associated with desaturation after adjusting for age, sex, andbody mass index.Conclusion: Nocturnal hypoxia is common in IPAH patients. Desaturation may aggravate the clinical situation of patients with IPAH. In IPAH patients, a poor exercise capacity (6 MWD) and the VE/VCO2 slope can predict desaturation after adjusting for age, sex, and body mass index.

Keywords: nocturnal hypoxia, desaturation, idiopathic pulmonary arterial hypertension

PartII The clinical characteristics of patients with pulmonary hypertension combined with obstructive sleep apnoea

Background: Obstructive sleep apnoea (OSA) is one cause of pulmonary hypertension (PH) and can also emerge along with PH. The clinical diagnosis and treatment of OSA in patients with PH are still controversial. The purpose of this clinical observation study was to observe and summarize the incidence and clinical characteristics of OSA in patients with PH and to explore possible predictors of PH combined with OSA. Methods: Patients with PH diagnosed by right heart catheterization who underwent overnight cardiorespiratory monitoring from December 2018 to December 2020 were enrolled. OSA was defned as an apnoea–hypopnoea index (AHI) ≥5/h with≥50% of apnoeic events being obstructive. Baseline clinical characteristics and parameters were collected to compare PH patients with and without OSA. Logistic regression analysis was run to determine the risk factors for OSA in PH patients. Results: A total of 35 (25%) of 140 patients had OSA. OSA is relatively frequent in patients with PH, especially in patients with chronic thromboembolic pulmonary hypertension (50%) and patients with lung disease– or hypoxia-associated PH (76%). The patients who had OSA were mostly male and had a higher age and a lower daytime arterial oxygen pressure. Logistic regression analysis found that older age, male sex, and lower daytime arterial blood oxygen pressure correlated with OSA in PH patients. Conclusion: OSA is common in patients with PH. Lower daytime arterial oxygen pressure is a risk factor for OSA in older male patients with PH.

Keywords: Pulmonary hypertension, Obstructive sleep apnoea, Risk factors

PartIII The Prognostic Impact of Serum Uric Acid on Disease Severity and 5-YearMortality in Patients with Idiopathic Pulmonary Artery Hypertension 

Background: Serum uric acid (UA) has long been identifified as a prognostic factorof adverse outcomes in pulmonary hypertension (PH). However, there remains a paucity of evidence on patients with idiopathic pulmonary artery hypertension (IPAH) in the era of targeted drug therapy. This study aims to explore the impact of serum UA levels on the disease severity and mortality in patients with IPAH. Methods: Consecutive patients diagnosed with IPAH were enrolled, from which UA levels at baseline and the first follow-up were collected. Patients were divided into groups of “hyperuricemia”, which is defifined as serum UA level ≥357 µmol/L in women and ≥420 µmol/L in men, and otherwise “normouricemia.” The potential relationship between UA and hemodynamics at right heart catheterization was investigated. Associations between UA and survival were evaluated by Kaplan-Meier analysis and Cox proportional hazard modeling. Results: Of 207 patients with IPAH, 121 (58.5%) had hyperuricemia. Higher serum UA levels were associated with lower cardiac index (r = 0.47, P < 0.001) and higher pulmonary vascular resistance (r = 0.36, P < 0.001). During a median follow-up of 34 months, there were 32 deaths recorded, accounting for a 15.5% mortality rate. Patients with hyperuricemia had a signifificantly lower survival rate than those with normouricemia (log-rank test, P = 0.002). Hyperuricemia at baseline was independently associated with a 2.6-fold increased risk of 5-year death, which was consistent across different subgroups, especially in females and those aged ≥30 years (each P < 0.05). Individuals with higher variability in UA had a higher mortality than those with stable UA (log-rank test, P = 0.024). Conclusions: Baseline hyperuricemia and high variability in serum UA at the first follow-up were related to a higher rate of 5-year mortality in patients with IPAH. Closely detecting the UA levels may aid in the early recognition of IPAH patients at higher mortality risk.

Keywords: hyperuricemia, IPAH, mortality, outcomes, pulmonary hypertension, uric acid.