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8th November 2021
Levels of three amino acids, glycine, phenylalanine and valine measured upon admission to an ED in patients admitted with dyspnoea are strongly predictive of 90-day mortality. This was the conclusion of a study by a team from the Department of Clinical Sciences, Lund University, Malmo, Sweden. Dyspnoea is a common presentation in an ED with one study of over 3,000 patients, finding that 5.2% of ED presentations, 11.4% of ward admissions and 19.9% of intensive care unit admissions were due to dyspnoea. There are a number of underlying conditions which can cause dyspnoea which presents as either an impaired ventilation or increased ventilatory demand, or some cases, both. Irrespective of the underlying cause, in patients with dyspnoea there is the release of stress hormones and metabolic changes, one of which is the induction of a catabolic state and insulin resistance.
Interestingly, some previous work has shown that the elevation of a combination of three amino acids could be used to successfully predict future diabetes. Based on these observations, the Lund University team hypothesised that the insulin resistance induced by stress in those with acute dyspnoea, would also alter levels of certain amino acids and that these alterations might be of valve in the assessment of dyspnoea severity and possibly even predictive of dyspnoea mortality.
In an effort to examine their hypothesis, the researchers retrospectively analysed patient data for those admitted to an ED with acute dyspnoea between 2013 and 2015. Plasma levels of nine amino acids were measured and Cox proportional hazard models used to explore the relationship between the level of these amino acids and the risk of 90-day mortality, which served as the primary endpoint for the study.
Data were analysed for a total of 663 patients with a mean age of 71.5 years (53.4% female), of whom 61% were admitted to a ward and 20.1% required intensive care treatment. Overall, 12% of patients died during the 90-day follow-up period. Only three amino acids of the original nine measured, demonstrated a significant association with 90-day mortality. These were glycine (hazard ratio, HR = 1.32, 95% CI 1.08 – 1.62, p < 0.001), phenylalanine (HR = 1.53) and valine (HR = 0.61).
Next, the researchers created an amino acid mortality risk score (AMRS) which was divided into quartiles and they found that in quartile 1, the 90-day mortality was 2.4% whereas it increased massively to 26.5% in quartile 4.
Commenting on these findings, the authors suggested that changes in the levels of these three amino acids, measured during presentation at the ED, were able to strongly predict 90-mortality in patients with acute dyspnoea, irrespective of the underlying cause. They concluded that a score using just these three amino acids could be used as a guide in risk assessment and to support decision-making to establish an appropriate level of care for patients presenting to an ED with acute dyspnoea.
Wiklund K et al. Amino acids predict prognosis in patients with acute dyspnea. BMC Emerg Med 2021