Getting to the Heart of the Matter

Coronary heart disease (CHD) is the world’s biggest killer – responsible for 16 percent of deaths globally. But determining those at risk can be a major challenge, as CHD shares symptoms with other cardiovascular conditions.

Although multiple tests of cardiovascular function and health exist, none alone can provide a complete overview of a patient’s state of cardiovascular health. But with the addition of a suitable biomarker, a group of clinicians at Duke University, North Carolina, hopes to pioneer a combinatorial approach. “We’re interested in seeing whether we can combine the testing we already do for patients at rest and during exercise stress tests with blood-based biomarkers to get additional information about the health of a patient’s heart,” explains Alexander Limkakeng Jr, Associate Professor of Surgery at Duke University Medical School, and a lead author of a paper describing the study (1).

Several groups had already carried out preliminary investigations using resting-state metabolites, including medium length fatty acids, but these biomarkers wouldn’t provide sufficient specificity, according to Limkakeng. “Such approaches are based on a one-time biomarker assessment,” he says. “We felt that serial biomarker assessment in the setting of stress tests would be more appropriate.” And so, Limkakeng and colleagues obtained samples for metabolomic analysis before and after stress testing from patients in the local emergency department to gain a chemical picture of what changes were occurring over time.

The team identified five metabolites – including the amino acid alanine - with a strong association to positive CHD stress test results, and several more with positive correlations. “We are now trying to obtain more samples to give our studies more statistical power, and to determine whether the metabolites we have identified can be used as biomarkers in the future,” he says. Future work will also refine the timescales involved in the testing and establish additional reference time points.

“We’re not yet ready for direct translation,” says Limkakeng. “But providing we find the right metabolite, biomarker or signature, there are very few barriers to implementing our approach in the stress testing we are already doing now.”