Repeated Measurements of Biomarkers May Improve Prognostic Accuracy in PAH-CHD Patients, Study Finds

Repeated measurements of different biomarkers over time offer a better risk prediction than single measurements for pulmonary arterial hypertension (PAH) associated with congenital heart disease, a study reports.

The study, “Prognostic value of multiple repeated biomarkers in pulmonary arterial hypertension associated with congenital heart disease,” was published in the European Journal of Heart Failure.

PAH is characterized by increased blood pressure in the arteries that go from the heart to the lungs, and is a frequent complication associated with congenital heart disease (CHD). The association between the two conditions involves many molecular mechanisms that can be explored through biomarkers.

Biomarkers can be easily measured from a blood sample without the need for an invasive procedure, and it can be done at low cost with high reproducibility.  Up until now, the European guidelines only included natriuretic peptides — small molecules released from the heart in response to pressure and volume overload — as biomarkers for PAH linked to cardiac diseases.

Instead of looking at a single biomarker, a team led by researchers at the University of Amsterdam Heart Centre in the Netherlands used a combination of biomarkers measured repeatedly to better track disease progression. The team hypothesized that changes in biomarkers over time should more accurately reflect disease status.

“The use of multiple biomarkers in combination (the so‐called ‘multimarker’ approach) may … be of greater prognostic value than a single biomarker approach,” they wrote.

To test their hypothesis, the researchers measured four candidate biomarkers: myocardial stress (N-terminal pro brain natriuretic peptide, or NT-proBNP), myocyte injury (high sensitive troponin T, or hs-TnT), cardio-renal dysfunction (cystain-C), and extracellular matrix remodeling (galectin-3).

These biomarkers were evaluated in 98 PAH-CHD patients with a mean age of 43 years. Blood samples were analyzed for the biomarkers every six to 12 months. Patients were followed for a median of 6.9 years.

During the study, 41 patients died, the majority of which was due to right heart failure (49%) and sudden cardiac death (12%).

Researchers found that the levels of the biomarkers analyzed in these patients increased progressively before death, compared with patients who remained alive during the study.

Excluding galactin-3, each biomarker demonstrated excellent predictive performance for 10-year mortality. However, the combination of repeated measurements of the best three biomarkers did not offer a prognostic gain over the individual biomarkers.

The team concluded that “risk prediction with repeated measurements was more accurate than with single measurements,” they wrote. Because chronic diseases such as CHD are such dynamic processes, the team argued that a single biomarker measure at one point in time is insufficient to make survival predictions.

“Our findings support the concept of regular assessment of at least one biomarker, e.g. NT-proBNP, to help identify patients with PAH-CHD at greatest risk,” they concluded.