Apelin-17 levels may be used for IPAH diagnosis, study shows
Peptide found to have similar accuracy to two established biomarkers
A peptide called apelin-17 may be used as a diagnostic biomarker for idiopathic pulmonary arterial hypertension (IPAH), according to the results of a new study.
Apelin-17 levels were found to detect IPAH with an accuracy similar to NT-proBNP and GDF-15 — two established biomarkers for pulmonary hypertension (PH) prognosis and risk assessment.
Further, blood levels of the peptide also were elevated in patients with another form of PH, the researchers noted.
“This finding suggests that apelin-17 may not only be a marker for IPAH but for pulmonary hypertension, in general,” the team wrote.
The study, “Apelin-17 to diagnose idiopathic pulmonary arterial hypertension: A biomarker study,” was published in the journal Frontiers in Physiology.
Apelin-17 peptide a new diagnostic biomarker for IPAH
PAH is characterized by the narrowing of pulmonary arteries — the blood vessels that transport blood to the lungs — which restricts blood flow and causes high blood pressure, or hypertension.
Several biomarkers derived from the blood have been predictive of PH, but not all are recommended according to international guidelines.
Aiming to find a biomarker with a unique diagnostic value, researchers in Austria now studied the potential of a peptide — a string of amino acids, the building blocks of proteins — called apelin. The apelin receptor is present in endothelial cells, the thin layer of cells that line blood vessels, as well as smooth muscle cells.
Here, the team focused on apelin-17, which has the highest binding potency to the apelin receptor.
Blood serum samples were collected from 31 patients with IPAH — when the disease cause is unknown— and 31 healthy people serving as controls. The study also included 24 patients with chronic thromboembolic pulmonary hypertension (CTEPH), a type of PH caused by blood clots.
Apelin-17 serum levels were elevated in both IPAH and CTEPH patients, compared with controls (median levels in picrograms per milliliter (pg/mL): IPAH: 1591, CTEPH: 1561; and controls: 921). For another apelin peptide, apelin-13, there were no differences between patients and controls.
The results were similar for GDF-15 and NT-proBNP, as their levels also were increased in the patients in comparison with the controls. The researchers noted that NT-proBNP values were not available in two IPAH patients, one CTEPH patient, and six healthy controls.
Using a cut-off value of 1480 pg/ml (higher levels corresponding to IPAH), apelin-17 levels could distinguish IPAH from controls with a sensitivity of 68% and a specificity of 93%. Sensitivity means the ability of a test to correctly identify patients with a disease, while specificity refers to the ability to identify those without the condition.
For a sensitivity of 86% and a specificity of 72%, the cut-off values for GDF-15 and NT-proBNP in detecting IPAH were 855 pg/ml and 140 pg/ml, respectively.
“As a main finding, we found that apelin-17 distinguished IPAH from controls with an [accuracy] comparable to NT-proBNP and GDF-15,” the researchers wrote.
In addition, apelin-17 was able to identify CTEPH patients with an accuracy comparable to IPAH.
This finding suggests that apelin-17 may not only be a marker for IPAH but for pulmonary hypertension, in general.
A model was used to combine the three markers to improve either sensitivity or specificity. Three positive criteria in the same patient — meaning apelin-17 higher than 1480 pg/ml, NT-proBNP higher than 140 pg/ml, and GDF-15 higher than 855 pg/ml — detected IPAH with a sensitivity of 41% and a specificity of 96%.
When two of these markers were above the cut-off value, the sensitivity to detect IPAH was 86% and the specificity was 80%. Meanwhile, when only one marker was above the cut-off, IPAH was detected with a sensitivity of 100% and a specificity of 60%.
Apelin-17 was not significantly correlated with demographic or blood flow data in IPAH patients. In contrast, NT-proBNP and GDF-15 positively correlated with each other and also with uric acid and world health organization functional classification.
In the CTEPH group, apelin-17 was positively correlated with markers of right heart failure (including NT-proBNP), uric acid, and bilirubin — a waste product made when hemoglobin in red blood cells is broken down. Both NT-proBNP and GDF-15 correlated with markers of blood flow and the 6-min walk distance, a standard measure of exercise capacity.
“Apelin-17 appears to be suitable blood derived diagnostic marker for idiopathic pulmonary arterial hypertension,” the team wrote.
According to the researchers, apelin-17 levels might be elevated in the whole disease course since the disease is progressive. Therefore, “future studies assessing apelin-17 as a prognostic biomarker in PH are warranted,” the researchers concluded.