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Elevated plasma phenylalanine predicts mortality in critical patients with heart failure.

ABSTRACT: AIMS:Previous studies found a relationship between elevated phenylalanine levels and poor cardiovascular outcomes. Potential strategies are available to manipulate phenylalanine metabolism. This study investigated whether increased phenylalanine predicted mortality in critical patients with either acute heart failure (HF) or acute on chronic HF, and its correlation with inflammation and immune cytokines. METHODS AND RESULTS:This study recruited 152 subjects, including 115 patients with HF admitted for critical conditions and 37 normal controls. We measured left ventricular ejection fraction (LVEF), plasma concentrations of phenylalanine, C-reactive protein, albumin, pre-albumin, transferrin, and pro-inflammatory and immune cytokines. Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and maximal vasoactive-inotropic scores (VISmax ) were calculated. Patients were followed up until death or a maximum of 1 year. The primary endpoint was all-cause death. Of the 115 patients, 37 (32.2%) were admitted owing to acute HF, and 78 (67.8%) were admitted owing to acute on chronic HF; 64 (55.7%) had ST elevation/non-ST elevation myocardial infarction. An LVEF measured during the hospitalization of <40%, 40-50%, and ?50% was noted in 51 (44.3%), 15 (13.1%), and 49 (42.6%) patients, respectively. During 1 year follow-up, 51 (44.3%) patients died. Death was associated with higher APACHE II, SOFA, and VISmax scores; higher levels of C-reactive protein and phenylalanine; higher incidence of atrial fibrillation and use of inotropic agents; lower cholesterol, albumin, pre-albumin, and transferrin levels; and significant changes in pro-inflammatory and immune cytokines. Phenylalanine levels demonstrated an area under the receiver operating characteristic curve of 0.80 for mortality, with an optimal cut-off value set at 112 ?M. Phenylalanine ? 112 ?M was associated with a higher mortality rate than was phenylalanine < 112 ?M (80.5% vs. 24.3%, P < 0.001) [hazard ratio = 5.07 (2.83-9.05), P < 0.001]. The Kaplan-Meier curves revealed that phenylalanine ? 112 ?M was associated with a lower accumulative survival rate (log rank = 36.9, P < 0.001). Higher phenylalanine levels were correlated with higher APACHE II and SOFA scores, higher C-reactive protein levels and incidence of using inotropic agents, and changes in cytokines suggestive of immunosuppression, but lower levels of pre-albumin and transferrin. Further multivariable analysis showed that phenylalanine ? 112 ?M predicted death over 1 year independently of age, APACHE II and SOFA scores, atrial fibrillation, C-reactive protein, cholesterol, pre-albumin, transferrin, and interleukin-8 and interleukin-10. CONCLUSIONS:Elevated phenylalanine levels predicted mortality in critical patients, phenotypically predominantly presenting with HF, independently of traditional prognostic factors and cytokines associated with inflammation and immunity.

SUBMITTER: Chen WS

PROVIDER: S-EPMC7524095 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Elevated plasma phenylalanine predicts mortality in critical patients with heart failure.

Chen Wei-Siang WS Wang Chao-Hung CH Cheng Chi-Wen CW Liu Ming-Hui MH Chu Chien-Ming CM Wu Huang-Ping HP Huang Pao-Chin PC Lin Yi-Tsen YT Ko Ta T Chen Wen-Hsin WH Wang Huei-Jen HJ Lee Shu-Chiu SC Liang Chung-Yu CY

ESC heart failure 20200702 5

<h4>Aims</h4>Previous studies found a relationship between elevated phenylalanine levels and poor cardiovascular outcomes. Potential strategies are available to manipulate phenylalanine metabolism. This study investigated whether increased phenylalanine predicted mortality in critical patients with either acute heart failure (HF) or acute on chronic HF, and its correlation with inflammation and immune cytokines.<h4>Methods and results</h4>This study recruited 152 subjects, including 115 patients ...[more]

PMID: 32618142

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Elevated plasma phenylalanine predicts mortality in critical patients with heart failure.

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Elevated plasma phenylalanine predicts mortality in critical patients with heart failure.

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