A new blood test could offer a quick glimpse into a person’s overall cardiovascular fitness, according to results published in Nature Medicine.
The test measures levels of proteins across metabolic, inflammatory, cardiovascular, pulmonary, and neurologic conditions to identify a signature related to the fitness level of an individual.
“This approach can yield a biomarker of fitness that may be universally applicable,” said Ravi Shah, M.D., senior author and a professor of cardiovascular medicine at Vanderbilt University Medical Center.
Simpler Answers
The blood test enables physicians to assess a patient’s overall heart health more simply. Fitness and exercise, while important, aren’t currently a part of modern clinical-risk equations, Shah said.
“Fitness level is strongly linked to a variety of diseases but is not actually currently incorporated into precision cardiovascular risk estimation. One reason for that might be that it takes dedicated time and testing to assess,” Shah explained.
“This approach can yield a biomarker of fitness that may be universally applicable.”
A quick blood test could complement exercise testing that might otherwise take more than 20 minutes in a clinical encounter, or it may serve as an initial assessment to inform more intensive testing orders, Shah says.
“This blood test might even be useful in individuals without symptoms looking for an estimation risk, which represents the majority of people we see in clinical practice,” he said.
A Wide Net
Shah and colleagues embarked on a trans-national study to develop the new blood test. They first wholly analyzed circulating proteins in 14,145 people across four international cohorts, and whittled down the list to those proteins associated with cardiorespiratory fitness (CRF) outcomes. The result was a “CRF score,” assigned to each study participant.
“Given that we were assessing a very broad human proteome, we knew our samples had to be collected from multiple settings to show that what we found is reproducible across different geographies, ages, outcome measures, and sampling strategies,” Shah said.
The researchers then validated their protein-based CRF score against health outcomes from 21,988 people in a separate biobank. This was essential to show that their proteomic measurements could stack up against other measures when predicting health outcomes.
“We observed a consistent and strong protective association of a greater proteomic CRF score for cardiovascular, metabolic and neurological outcomes,” they wrote. “Moreover, the proteomic CRF score improved risk prediction beyond standard risk factors, with improved discrimination and reclassification across nearly every endpoint.”
Clinic Utility
The next step, Shah said, was to further pare down the proteins and bring the CRF score to something that could be deployed in the clinic. The authors reduced their CRF score to 21 proteins, validating the smaller protein panel in people who participated in a 20-week exercise program. The CRF scores shifted with exercise training, demonstrating the test’s dynamism. The findings highlight the utility of a simplified, proteomic approach to cardiovascular fitness.
Ongoing Effort
The work builds upon other efforts to uncover biomarkers of physical fitness, such as that supported by the NIH’s Molecular Transducers of Physical Activity Consortium (MoTrPAC).
Shah and colleagues are also working on a follow-up study to tease apart insights from protein-based blood testing and traditional exercise testing and how these measures can practically complement each other at point-of-care.
Long-term, Shah envisions proteome assessments working similarly to polygenic risk scoring.
“It’s akin to when you survey the human genome to get an idea of the genetic susceptibility you as a patient might have for a certain disease,” he said. “The protein is one step closer to the phenotype and may reflect what’s going on at that time across your entire body.
“I think what’s going to happen in the future is that this type of blood test – the proteome – may complement human genetics to capture risk more precisely in the clinic.”
