Markers of Vascular Remodeling May Help Predict PAH in Early Stages

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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The blood levels of two molecules involved in vascular remodeling, a hallmark feature of pulmonary arterial hypertension (PAH), may be used as noninvasive predictive biomarkers of the disease, a small study suggests.

The study, “Fibrinolytic markers could be useful predictors of severity in patients with pulmonary arterial hypertension: a retrospective study,” was published in the Thrombosis Journal.

PAH is characterized by the narrowing of the pulmonary arteries, restricting blood and oxygen flow and raising blood pressure (hypertension). This arterial narrowing is the result of pulmonary vascular remodeling, a process that involves the uncontrolled growth of smooth muscle cells, progressively thickening the arterial walls.

Currently, PAH is defined as a mean pulmonary artery pressure (mPAP) of 25 mmHg (millimeters of mercury) or higher, as measured by right heart catheterization (RHC) — an invasive method to assess how well the heart is pumping and to evaluate pressure in the heart and lungs. Also, mPAP is an accurate predictive biomarker of PAH, as well as a marker of its severity.

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Given the invasive nature of RHC, noninvasive biomarkers to detect PAH early are needed.

Now, a team of researchers in Japan have evaluated whether the blood levels of two molecules involved in vascular remodeling — total plasminogen activator inhibitor-1 (tPAI-1) and thrombomodulin (TM) — were significantly associated with mPAP and therefore showed potential to be used as predictive markers of PAH.

Both tPAI-1 and TM are mainly known for their role in fibrinolysis, a process that prevents blood clotting and that is sometimes impaired in pulmonary hypertension (PH). However, increasing evidence has highlighted their involvement in vascular and artery remodeling.

The researchers retrospectively analyzed mPAP levels, as well as those of tPAI-1 and TM, in 100 adults (62 women and 38 men) who underwent RHC to assess cardiac function. The blood levels of uric acid — a normal waste product that has been associated with PAH — were also analyzed.

The mean average age of the participants was 68.9 years, and the most common underlying condition was heart failure (30%). Seven patients (7%) had been diagnosed with respiratory diseases, and five (5%) had PH of unknown cause.

Results showed that the participants’ average mPAP value was 25.1 mmHg, with 42 of them having levels above the PAH threshold (25 mmHg) and 58 being under that value.

Higher mPAP values were significantly associated with higher tPAI-1 and uric acid levels, but not with those of TM. In addition, patients not surpassing the PAH threshold had significantly lower levels of tPAI-1 and uric acid relative to those with PAH.

However, only tPAI-1 was found to be an independent marker of PAH after adjusting for potential influencing factors, such as age, sex, and body mass index.

Moreover, a significant link between mPAP and both tPAI-1 and TM was found among the group of patients below the PAH threshold.

These findings suggest that blood levels of tPAI-1 and TM could be potential noninvasive predictive markers “of severity in patients with PAH, especially in their early stages with mPAP levels less than 25 mmHg,” the researchers wrote.

Larger studies are needed to confirm these findings, the team noted.