Study IDs 2 possible markers of PAH prognosis, treatment response
Blood levels of angiopoietin-2, D-dimer show risk of worse patient outcomes
Blood levels of angiopoietin-2, a marker of blood vessel damage, may help predict treatment response and outcomes in pulmonary arterial hypertension (PAH), according to a new study from researchers in the U.S.
Levels of D-dimer, a marker of blood clot formation, were also increased in PAH patients, the study found. This added to an increased risk of worse outcomes — such as a need for lung transplant or hospitalization — when angiopoietin-2 levels were high.
“Angiopoietin-2 and D-dimer … may add prognostic information to routine clinical assessment,” the researchers wrote, adding that “future work in biomarkers will need to determine which readily measurable proteins add value to the robust clinical scoring systems we are already using.”
The study, “Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertension,” was published in the journal JHLT Open.
Investigating whether PAH disease markers can predict treatment response
PAH is a type of pulmonary hypertension characterized by the narrowing of the pulmonary arteries, which are the blood vessels that supply the lungs. Such narrowing restricts blow flow across the lungs, leading to high blood pressure, known as hypertension, and right heart failure.
Although the disease’s causes are not fully known, blood vessel inflammation, damage to endothelial cells that line the interior surface of blood vessels, and the formation of blood clots, are all thought to play a role in its development.
To learn more, a team led by researchers at the University of Rochester Medical Center in New York launched a study that enrolled 86 PAH patients and 12 healthy people, who served as controls. The researchers’ goal was to evaluate whether markers of blood coagulation and endothelial dysfunction could inform disease activity and treatment response.
The participants were mainly women (71%), with a median age of 61. Slightly more than half of the patients (52%) had idiopathic PAH, meaning the disease’s cause was unknown. One-third (32%) had PAH associated with connective tissue disorders, known as CTD-related PAH.
Additionally, one-quarter of patients — 22, or 25.6% — were initially categorized as untreated, or treatment naïve. A total of 45 were treated and clinically stable, while 19 required treatment intensification.
Compared with the healthy controls, the PAH patients had elevated blood levels of angiopoietin-2; this was seen in both idiopathic and CTD-related PAH patients.
When patients started or intensified therapy and experienced clinical improvement, defined as a drop in Reveal Lite 2.0 score, angiopoietin-2 levels significantly decreased, the data showed. Reveal Lite 2.0 is a risk assessment tool that may help determine whether treatment escalation is needed, based on markers of heart damage, vital signs, exercise capacity, and kidney function.
[Angiopoietin-2] levels as a marker … were treatment responsive and prognostically significant even in those with a ‘low-risk’ … score [on assessments]. … This marker may represent an important risk stratification tool [in PAH].
In low-risk patients, high angiopoietin-2 levels — levels higher than those in 90% of the healthy controls — were associated with worse outcomes. These were a shorter event-free survival, which is time from the study’s start to the occurrence of PAH-related hospitalization, lung transplant, or death.
The levels of D-dimer, a protein fragment that forms when blood clots are present in the blood, were also elevated in PAH patients, but they did not change with treatment. Taking angiopoietin-2 and D-dimer together, patients with high levels of both markers had a significantly lower event-free survival, the study found.
However, D-dimer only contributed to changes in event-free survival in those with elevated angiopoietin-2.
Levels of soluble P-selectin — released from endothelial cells and platelets — and of vascular cell adhesion molecule-1, known as VCAM-1 and also present in endothelial cells, were also elevated in the PAH patients. However, they did not change with treatment or predicted disease outcomes.
“[Angiopoietin-2] levels as a marker of endothelial injury were treatment responsive and prognostically significant even in those with a ‘low-risk’ Reveal Lite 2 score,” the researchers wrote. “This marker may represent an important risk stratification tool.”
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