Department of Medicine, University of California-San Francisco, San Francisco, California, USA.
Department of Mathematical Sciences, University of Texas at Dallas, Richardson, Texas, USA.
Liver Transpl. 2024 Jul 1;30(7):679-688. doi: 10.1097/LVT.0000000000000359. Epub 2024 Mar 27.
Mean arterial blood pressure (MAP), which decreases as portal hypertension progresses, may be a modifiable risk factor among patients with cirrhosis. We included adults enrolled in the Functional Assessment in Liver Transplantation study. We completed latent class trajectory analyses to define MAP trajectories. We completed time-dependent Cox-regression analyses to test the association between outpatient MAP and 3 cirrhosis-related outcomes: (1) stage 2 acute kidney injury (AKI), defined as a ≥200% increase in serum creatinine from baseline; (2) a 5-point increase in the MELD-Na score, defined as the incidence of increase from initial MELD-Na; (3) waitlist mortality, defined as death on the waitlist. For each outcome, we defined MAP cut points by determining the maximally selected Log-rank statistic after univariable Cox-regression analyses. Among the 1786 patients included in this analysis, our latent class trajectory analyses identified 3 specific outpatient MAP trajectories: "stable-low," "stable-high," and "increasing-to-decreasing." However, >80% of patients were in a "stable-low" trajectory. We found in adjusted analyses that outpatient MAP was associated with each of our outcomes: Stage 2 AKI (adjusted hazard ratio 0.88 per 10 mm Hg increase in MAP [95% CI: 0.79-0.99]); 5-point increase in MELD-Na (adjusted hazard ratio: 0.91 [95% CI: 0.86-0.96]; waitlist mortality (adjusted hazard ratio: 0.89 [95% CI: 0.81-0.96]). For each outcome, we found that an outpatient MAP of 82 mm Hg was most associated with outcomes ( p <0.05 for all). Our study informs the association between outpatient MAP and cirrhosis-related outcomes. These findings, coupled with the identification of specific thresholds, lay the foundation for the trial of targeted outpatient MAP modulation in patients with cirrhosis.
平均动脉压(MAP)随着门静脉高压的进展而降低,可能是肝硬化患者的一个可改变的危险因素。我们纳入了参加功能评估肝移植研究的成年人。我们完成了潜在类别轨迹分析来定义 MAP 轨迹。我们完成了时间依赖性 Cox 回归分析来检验门诊 MAP 与 3 个肝硬化相关结局之间的关联:(1)第 2 期急性肾损伤(AKI),定义为血清肌酐从基线水平升高≥200%;(2)MELD-Na 评分增加 5 分,定义为初始 MELD-Na 增加;(3)等待名单死亡率,定义为等待名单上的死亡。对于每个结局,我们通过在单变量 Cox 回归分析后确定最大选择对数秩统计量来确定 MAP 切点。在这项分析中纳入的 1786 例患者中,我们的潜在类别轨迹分析确定了 3 种特定的门诊 MAP 轨迹:“稳定低”、“稳定高”和“先升后降”。然而,超过 80%的患者处于“稳定低”轨迹。我们发现,在调整分析中,门诊 MAP 与我们的每个结局相关:第 2 期 AKI(MAP 每增加 10mmHg,调整后的危险比为 0.88[95%CI:0.79-0.99]);MELD-Na 增加 5 分(调整后的危险比:0.91[95%CI:0.86-0.96]);等待名单死亡率(调整后的危险比:0.89[95%CI:0.81-0.96])。对于每个结局,我们发现 MAP 为 82mmHg 时与结局最相关(所有 p<0.05)。我们的研究阐明了门诊 MAP 与肝硬化相关结局之间的关联。这些发现,加上特定阈值的确定,为肝硬化患者的靶向门诊 MAP 调节试验奠定了基础。