Circular RNA Molecule May Help Diagnose, Predict Clinical Outcomes in IPAH, Study Suggests

Levels of a circular RNA molecule in the blood could help diagnose and predict the clinical outcomes of those with idiopathic pulmonary arterial hypertension (IPAH), a study suggests.

The study, “Elevated serum circ_0068481 levels as a potential diagnostic and prognostic indicator in idiopathic pulmonary arterial hypertension,” was published in the journal Pulmonary Circulation.

IPAH is a form of pulmonary hypertension (PH) whose specific root cause is not clear. Diagnosing and assessing the prognosis of those with IPAH can be challenging, particularly because this often requires invasive tests, like right heart catheterization. That procedure, a standard diagnostic in PH, measures the pressure in the arteries of the lungs and assesses the heart’s capacity to pump blood.

Given the difficulties of the current tests, there is a need for less invasive procedures that may facilitate the identification and prediction of clinical outcomes in people with IPAH.

Levels of biomarkers found in the blood are well-suited to non-invasive testing, since blood can be collected with relative ease.

Among such biomarkers are circular RNAs, which, as their name suggests, are RNA molecules that have a circular structure. Unlike linear RNA molecules that are used as a template for the production of proteins, circular RNAs typically do not provide instructions for making proteins and are thought to control the activity of certain genes.

Circular RNAs are often viewed as well-suited biomarkers because their circular structure enhances their stability in the blood. For this reason, many of these molecules are currently being investigated as biomarkers in several medical conditions, including heart disease and cancer.

A circular RNA called circ_0068481, in particular, was found to be present at relatively high levels in people with chronic thromboembolic pulmonary hypertension (CTEPH), a rare form of PH caused by the formation of blood clots.

Now, Chinese researchers investigated whether circ_0068481 might hold similar utility as a biomarker of IPAH.

To explore that possibility, the researchers measured the levels of circ_0068481 in 82 people with IPAH, who were followed at the Guangdong Provincial People’s Hospital, in China, between 2016 and 2018. Investigators also measured the levels of circ_0068481 in 82 individuals without IPAH or other known medical conditions (healthy control group) of the same sex and age.

In addition to circ_0068481 levels, the team also analyzed patients’ clinical data, including hemodynamic (blood flow and pressure) and biochemical parameters.

The results showed that, on average, circ_0068481 levels were significantly higher in IPAH patients than in healthy controls.

In an optimized statistical model, the researchers found that using circ_0068481 levels as a biomarker to identify people with IPAH had a high sensitivity (74.39%, meaning the percentage of patients correctly identified), and high specificity (98.78%, meaning the percentage of healthy people who are correctly identified as not having the condition).

In subsequent analyses, researchers divided the IPAH patients into two groups based on their circ_0068481 levels: 41 who had the highest levels were placed in one group while the remaining 41, who had the lowest levels, were in assigned to the other group.

Although many clinical features, such as age, sex, body mass index, and average pulmonary arterial pressure, did not differ between the two groups, those who had the highest levels of circ_0068481 had significantly lower scores on the six-minute walk test (387.3 versus 496.5 meters, or about 1271 versus 1629 feet). This suggested a loss of physical fitness.

Moreover, a higher number of those who had the highest levels of circ_0068481 were classified as having a “moderate” or “severe” disease risk based on the WSPH risk stratification, compared with those who had the lowest levels of circ_0068481 (38 versus 25 patients).

The researchers also found that significantly more people in the higher level group had right heart failure (28 versus 1). All 16 patients who passed away during the study were members of the higher level group.

“These results suggest that circ_0068481 can predict poor clinical outcome in patients with IPAH,” the investigators said, suggesting that it is “a novel and noninvasive biomarker for diagnosing idiopathic pulmonary arterial hypertension.”

However, according to the team, additional studies with larger populations are needed to validate these findings. More research also is needed to address important questions, including assessing whether circ_0068481 levels may change in response to treatment.