Metabolic panels of 14 blood-based biomarkers that can predict when a patient is likely to die may be coming to a medical laboratory near you

Clinical pathologists soon may be able to predict when patients will die, thanks to a recent study that reveals new insights into how the human body works. Researchers at the Max Planck Institute for Biology of Ageing in Germany and the Leiden University Medical Center (LUMC) in the Netherlands revealed a metabolic panel of biomarkers that can more accurately predict death within five to 10 years than standard measures.

The researchers’ original goal was to find blood-based biomarkers that could show whether a person was vulnerable to death, particularly if that vulnerability was related to modifiable lifestyle factors.

The researchers published their study, titled, “A Metabolic Profile of All-Cause Mortality Risk Identified in an Observational Study of 44,168 Individuals,” in the journal Nature Communications last August.

Metabolic Biomarkers More Accurate than Current Health Measures

During their investigation, the researchers looked at 12 cohorts from previous studies and examined the results of 44,168 individuals between the ages of 18 and 109. In the follow-up to the study, 5,512 of the participants died.

In the introduction to their published study the researchers wrote, “We first determine which metabolic biomarkers independently associate with prospective mortality in all individuals. Subsequently, we test the association of the biomarkers with mortality in different age strata.”

The researchers then used the 14 biomarkers they identified to create a score that predicts mortality within five to 10 years.

The measures that most providers currently use to determine an elderly person’s overall health generally include blood pressure, heart rate, and functionality measures such as grip strength and gait. However, P. Eline Slagboom, PhD, LUMC Professor of Molecular Epidemiology and the study’s director, told The Scientist that those metrics are not always accurate methods for measuring health.

“For example, a somewhat higher weight, blood pressure, or cholesterol level is not as bad for individuals over 80 years of age as compared to younger individuals,” she said.

As it turned out, the traditional measures were significantly less accurate than the score Slagboom and her team developed. Traditional measures were accurate about 78% of the time, while the metabolic panel was accurate about 83% of the time, reported The Scientist. Additionally, the score based on metabolic biomarkers was accurate for people of all ages, rather than only among the young.

“As researchers on aging, we are keen to determine the biological age. The calendar age just doesn’t say very much about the general state of health of elderly people: one 70-year old is healthy, while another may already be suffering from three diseases. We now have a set of biomarkers which may help to identify vulnerable elderly people,” said P. Eline Slagboom, PhD (above), LUMC Professor of Molecular Epidemiology and the study’s director, in a statement. (Photo copyright: Max Planck Institute for Biology of Ageing.)

Study Yields Strong but Surprising Results

Researchers have studied biomarkers as predictive tools for quite some time, with only narrow success. The positive results of the Max Planck Institute/LUMC study even surprised those who worked on it. “We were surprised that the association of our biomarker score with mortality was so strong, given that it is only based on 14 metabolic markers in the blood measured at a single point in the life of individuals,” the study’s lead author Joris Deelen, PhD, a postdoctoral researcher at the Max Planck Institute for Biology of Ageing, said in The Scientist.

But though the results of the study are intriguing, some experts remain skeptical that a new biomarker for death has been found.

In reactions published by the Science Media Centre, an independent organization in the UK that promotes “the reporting of evidence-based science,” Kevin McConway, PhD, Emeritus Professor of Applied Statistics at The Open University wrote, “This is a solid and interesting piece of research. But it doesn’t go beyond investigating the plausibility of setting up a system for predicting risk of death, based on this type of data. It doesn’t claim to do more than that, and makes clear that there’s some way to go, in terms of research and analysis, until a risk prediction tool that’s useable in clinical work with patients might emerge.”

And in the same article, Amanda Heslegrave, PhD, a post-doctoral research associate and researcher at the UK Dementia Research Institute at the University College London wrote, “Whilst this study shows that this type of profiling can be useful, [the researchers] do point out importantly that it would need further work to develop a score at the individual level that would be useful in real life situations. We’d need to see: validation to ensure repeatability in different labs, production of reference samples to test this on an ongoing basis, work to make the individual score possible, validation in other cohorts and validation of all components of the panel. So, it’s an exciting step, but it’s not ready yet.”

Past Mortality Biomarker Studies

Other investigations into the use of biomarkers as a predictive tool have focused more narrowly on specific causes of death. For example, in 2008, the New England Journal of Medicine (NEJM) published a study titled, “Use of Multiple Biomarkers to Improve the Prediction of Death from Cardiovascular Causes.” The study concluded that using biomarkers and risk factors together “substantially improves the risk stratification for death from cardiovascular causes.”

Another study, from 2017, examined stress biomarkers, hospital readmission, and death. Published in the Journal of Hospital Medicine titled, “Association of Stress Biomarkers with 30-Day Unplanned Readmission and Death,” the researchers found that “stress biomarkers improved the performance of prediction models and therefore could help better identify high-risk patients.”

Other studies have examined the predictive possibilities of biomarkers in:

Even with all of the research into biomarkers, scientists are still a long way from having a clinical tool to predict death. However, according to Leo Cheng, PhD, Associate Biophysicist, Pathology and Radiology at Massachusetts General Hospital, and Associate Professor of Radiology at Harvard Medical School, the Max Planck study is on the right path.

The Scientist states that though Cheng believes the study doesn’t “prove anything,” he also notes that “using a score that combines the information from all 14 biomarkers is ‘the correct thing [to do]’ to provide a holistic look at metabolic pathways that may represent a person’s health.”

So, it might be awhile before clinical laboratories will be processing metabolic panels that return test results predicting a patient’s mortality within 10-15 years. Nevertheless, how medical labs would be involved in such testing is certainly something to think about.

—Dava Stewart

Related Information:

A Metabolic Profile of All-Cause Mortality Risk Identified in an Observational Study of 44,168 Individuals

Biomarkers Indicate Health in Old Age

Metabolic Biomarker “Score” May Predict Death in Next 5-10 Years

Expert Reaction to Study Looking at Mortality Associated Biomarkers in the Blood

Use of Multiple Biomarkers to Improve the Prediction of Death from Cardiovascular Causes

Association of Stress Biomarkers with 30-Day Unplanned Readmission and Death

Opioid Deaths: Trends, Biomarkers, and Potential Drug Interactions Revealed by Decision Tree Analysis

Dr. Christopher DeGiorgio: Sudden Unexpected Death in Epilepsy: Risk Factors, Biomarkers, and Prevention

Biomarkers to Predict Causes of Death in Atrial Fibrillation