Observational studyCritical care medicine2022
Stress Hyperphenylalaninemia Is Associated With Mortality in Cardiac ICU: Clinical Factors, Genetic Variants, and Pteridines.
Observational study in Critical care medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Distinct microbial and metabolic shifts characterize acute coronary syndrome and recovery.iMeta · 2025Article
- Plasma phenylalanine is associated with hospital mortality in acute respiratory distress syndrome: a prospective metabolic profiling cohort study.European journal of medical research · 2025Observational
- L-Phenylalanine promotes liver steatosis by inhibiting BNIP3-mediated mitophagy.Molecular medicine (Cambridge, Mass.) · 2025Article
- Low, Intermediate, and High Glutamine Levels Are Progressively Associated with Increased Lymphopenia, a Diminished Inflammatory Response, and Higher Mortality in Internal Medicine Patients with Sepsis.Journal of clinical medicine · 2025Article
- Multiplatform Metabolomics: Enhancing the Severity Risk Prognosis of SARS-CoV-2 Infection.ACS omega · 2024Article
- Extensive Dysregulation of Phenylalanine Metabolism Is Associated With Stress Hyperphenylalaninemia and 30-Day Death in Critically Ill Patients With Acute Decompensated Heart Failure.Journal of the American Heart Association · 2024Article
- Prognostic Significance of Phenylalanine in Heart Failure: Clinical Insights and Inter-Organ Crosstalk Snapshot.Journal of clinical medicine · 2024Article
- Association of phenylalanine and tyrosine metabolism with mortality and response to nutritional support among patients at nutritional risk: a secondary analysis of the randomized clinical trial EFFORT.Frontiers in nutrition · 2024Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesHyperphenylalaninemia 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.
designProspective observational study.
settingSingle-center, cardiac ICU in Taiwan. PATIENTS: 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.
interventionsWe 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. MEASUREMENTS AND MAIN
resultsThe 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.
conclusionsSHP 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.
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