Novel index to predict mortality and inform malnutrition?

In the 1974 landmark publication The Skeleton in the Hospital Closet, the physician Charles E Butterworth described his observations of the pervasiveness and consequences of malnutrition in clinical populations.1Butterworth Jr, CE The skeleton in the hospital closet. 1974.Nutr Hosp. 2005; 20: 302-307PubMed Google Scholar Empirical evidence illustrating the burden of malnutrition on patient care followed, and were corroborated in subsequent reports, detailing consequences on mortality and hospital costs.2Hudson L Chittams J Griffith C Compher C Malnutrition identified by Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition is associated with more 30-day readmissions, greater hospital mortality, and longer hospital stays: a retrospective analysis of nutrition assessment data in a major medical center.JPEN J Parenter Enteral Nutr. 2018; 42: 892-897PubMed Google Scholar Nearly 50 years later, malnutrition persists as a major factor in patient care, with a crucial disconnect between coded malnutrition diagnosis and estimated prevalence. Only about 9% of patients treated in hospital have a coded diagnosis of malnutrition,3Guenter P Abdelhadi R Anthony P et al.Malnutrition diagnoses and associated outcomes in hospitalized patients: United States, 2018.Nutr Clin Pract. 2021; 36: 957-969Crossref PubMed Scopus (35) Google Scholar although estimates of prevalence are much higher, ranging from 25% to 50%.4Pfau PR Rombeau JL Nutrition.Medi Clin North Am. 2000; 84: 1209-1230Summary Full Text Full Text PDF PubMed Scopus (13) Google Scholar One reason for this disconnect is that no effective biomarker of malnutrition exists. Plasma acute phase proteins historically associated with nutritional status, such as albumin, have proven ineffective and are no longer considered reliable indicators of malnutrition.5Keller U Nutritional laboratory markers in malnutrition.J Clin Med. 2019; 8: 775Crossref PubMed Scopus (266) Google Scholar Similarly, other plasma multimarker indices6Ignacio de Ulibarri J Gonzalez-Madrono A de Villar NG et al.CONUT: a tool for controlling nutritional status. First validation in a hospital population.Nutr Hosp. 2005; 20: 38-45PubMed Google Scholar or alternative sources of metabolites, such as the exhaled breath,7Mey JT Rath MC McLaughlin K et al.The breath print represents a novel biomarker of malnutrition in pulmonary arterial hypertension: a proof of concept study.JPEN J Parenter Enteral Nutr. 2021; 45: 1645-1652Crossref Scopus (2) Google Scholar have not been proven to have clinical utility. Without an effective biomarker, malnutrition screening and identification relies on self-reported questionnaires and physical examinations, methods that are archaic in other nutrition-related and metabolic diseases (eg, glycated haemoglobin for diabetes). The lack of a malnutrition biomarker accentuates the knowledge gap of the underlying biological mechanisms of malnutrition. Thus, the identification of a malnutrition biomarker is of prime clinical and research interest. In a study published in The Lancet Healthy Longevity, James D Otvos and colleagues8Otvos JD Shalaurova I May HT et al.Multimarkers of metabolic malnutrition and inflammation and their association with mortality risk in cardiac catheterisation patients: a prospective, longitudinal, observational, cohort study.Lancet Healthy Longev. 2023; 4: e72-e82Summary Full Text Full Text PDF Scopus (2) Google Scholar developed a novel multimarker index (the metabolic vulnerability index [MVX]) using a clinical nuclear magnetic resonance (NMR) spectroscopy platform. The MVX is composed of six simultaneously measured plasma metabolites and was shown to predict 5-year mortality risk in cardiovascular patients. Notably, the MVX outperformed established mortality predictors, including age. The strength of this predictive capacity is stunning, given the robust methods utilised: the MVX was developed and corroborated in two large, prospective cohorts from the CATHeterization GENetics (CATHGEN; n=5876) and Intermountain Heart Collaborative Study (n=2888), including a total of 1441 deaths within the 5-year mortality analysis. Further, the strength of the MVX mortality prediction persisted in the lowest-risk subgroups, suggesting it might be detecting previously unidentified factors of mortality risk. This novel index is particularly exciting because it might be relevant to current clinical gaps regarding malnutrition. In addition to their primary findings predicting 5-year mortality, the authors propose that the components of the MVX are biomarkers of “metabolic malnutrition–inflammation syndrome”, a term the authors use to distinguish the underlying metabolic aspects of malnutrition (eg, protein energy wasting) rather than the manifestation of diagnostic malnutrition criteria. If the MVX does indeed represent the underlying metabolic aspects of malnutrition, it has the potential to address two important needs: the addition of a new dimension (plasma indicator) to malnutrition diagnostic criteria, which currently rely on self-reported questionnaires and physical examinations, and provision of an indicator of the underlying biology of malnutrition for screening and risk assessment. The six MVX metabolites are small-size HDL particles, a composite NMR signal of acute-phase glycoproteins, citrate, leucine, isoleucine, and valine. These metabolites are indicators of inflammation and protein metabolism, which might capture both the output and input components of malnutrition—ie, hypermetabolism or catabolism and inadequate nutritional intake. For the MVX to evolve to clinical malnutrition utility, it must overcome the barriers that have hindered other plasma markers. First, a biomarker must be sensitive to changes in status. Is the MVX associated with clinical criteria consistent with “metabolic malnutrition–inflammation syndrome”—eg, clinical indicators of protein energy wasting or malnutrition? Will the MVX track with the severity or resolution of these indicators—eg, through resolved hypermetabolism or catabolism and improved nutritional intake? Second, the methods used to measure the MVX must avoid confounding from acute nutritional intake. The amino acid components of the MVX are sensitive to acute changes in nutritional status—eg, meal-by-meal protein quantity or amino acid composition. Of note, the magnitude of difference of plasma amino acid concentrations in participants stratified by 5-year survival status was small (<20 μmol/L) in comparison with the dynamic range of plasma amino acids after meals (>200 μmol/L).8Otvos JD Shalaurova I May HT et al.Multimarkers of metabolic malnutrition and inflammation and their association with mortality risk in cardiac catheterisation patients: a prospective, longitudinal, observational, cohort study.Lancet Healthy Longev. 2023; 4: e72-e82Summary Full Text Full Text PDF Scopus (2) Google Scholar For malnutrition biomarker assessment, an overnight fast might be useful in future research to improve the accuracy and reproducibility of the MVX measurement, as opposed to the 6 h fast implemented in the CATHGEN study. Independently of its potential within malnutrition, the MVX composite biomarker score is a clinically available tool that could lead to further research on understanding the causes of mortality risk in chronic disease. I declare no competing interests. Multimarkers of metabolic malnutrition and inflammation and their association with mortality risk in cardiac catheterisation patients: a prospective, longitudinal, observational, cohort studyMVX made a dominant contribution to mortality prediction in patients with cardiovascular disease and in low-risk subgroups without pre-existing disease, suggesting that metabolic malnutrition–inflammation syndromes might have a more universal role in survival than previously thought. Full-Text PDF Open Access