Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan.
School of Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Crit Care Med. 2022 Nov 1;50(11):1577-1587. doi: 10.1097/CCM.0000000000005640. Epub 2022 Aug 1.
Hyperphenylalaninemia predicts poor outcomes in patients with cardiovascular disease. However, the prognostic value and factors associated with stress hyperphenylalaninemia (SHP) were unknown in critical patients in the cardiac ICU.
Prospective observational study.
Single-center, cardiac ICU in Taiwan.
Patients over 20 years old with Acute Physiology And Chronic Health Evaluation II scores greater than or equal to 15 and/or ventilatory support in the cardiac ICU.
We measured plasma phenylalanine levels serially during patients' stays in the ICU to investigate their prognostic value for 90-day mortality. Gene array was performed to identify genetic polymorphisms associated with SHP (phenylalanine level ≥ 11.2 μmol/dL) and to develop a Genetic Risk Score (GRS). We analyzed the associations between SHP and clinical factors and genetic variants and identified the correlation between pteridines and genetic variants.
The study enrolled 497 patients. Increased phenylalanine concentration was independently associated with increased mortality risk. Patients with SHP had a higher mortality risk compared with those without SHP (log rank = 41.13; p < 0.001). SHP was associated with hepatic and renal dysfunction and with genetic polymorphisms on the pathway of tetrahydrobiopterin (BH4) synthesis (CBR1 and AKR1C3) and recycling (PCBD2). Higher GRSs were associated with lower BH4 bioavailability in response to stress ( p < 0.05). In patients without SHP at baseline, those with GRSs gretaer than or equal to 2 had a higher frequency of developing SHP during the ICU stay (31.5% vs 16.1%; p = 0.001) and a higher mortality risk ( p = 0.004) compared with those with GRSs less than 2. In patients with SHP at baseline, genetic variants did not provide additional prognostic value.
SHP in patients admitted to the ICU was associated with a worse prognosis. In patients without SHP, genetic polymorphisms associated with SHP measured using a GRS of greater than or equal to 2 was associated with the subsequent SHP and higher mortality risk.
高苯丙氨酸血症可预测心血管疾病患者的不良预后。然而，在心脏重症监护病房（ICU）的重症患者中，应激性高苯丙氨酸血症（SHP）的预后价值和相关因素尚不清楚。
前瞻性观察研究。
台湾的单中心心脏 ICU。
年龄大于 20 岁，急性生理学和慢性健康评估 II 评分大于或等于 15 分，且需要在心脏 ICU 进行通气支持的患者。
我们在 ICU 住院期间连续测量患者的血浆苯丙氨酸水平，以探讨其对 90 天死亡率的预后价值。进行基因芯片分析以确定与 SHP（苯丙氨酸水平≥11.2 μmol/dL）相关的遗传多态性，并制定遗传风险评分（GRS）。我们分析了 SHP 与临床因素和遗传变异之间的相关性，并确定了蝶呤与遗传变异之间的相关性。
本研究共纳入 497 例患者。苯丙氨酸浓度升高与死亡率升高独立相关。与无 SHP 的患者相比，有 SHP 的患者死亡率更高（对数秩检验=41.13；p<0.001）。SHP 与肝肾功能障碍以及四氢生物蝶呤（BH4）合成（CBR1 和 AKR1C3）和循环（PCBD2）途径的遗传多态性相关。较高的 GRS 与应激时 BH4 生物利用度降低相关（p<0.05）。在基线时无 SHP 的患者中，GRS 大于或等于 2 的患者在 ICU 住院期间发生 SHP 的频率更高（31.5%比 16.1%；p=0.001），死亡率更高（p=0.004）与 GRS 小于 2 的患者相比。在基线时有 SHP 的患者中，遗传变异并未提供额外的预后价值。
ICU 收治的患者中 SHP 与预后不良相关。在无 SHP 的患者中，使用 GRS 大于或等于 2 测量与 SHP 相关的遗传多态性与随后发生的 SHP 和更高的死亡率风险相关。
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