Potential non-invasive screening biomarker for SSc-PAH

By Lucy Piper

Serum asymmetric dimethylarginine (ADMA) may be an effective non-invasive screening biomarker for systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH), study findings indicate.

They also showed that when teamed with the well-studied candidate biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP), ADMA identified incident SSc-PAH with an "excellent" sensitivity and specificity of 100% and 90%, respectively.

"One of [the] factors impeding the wider use of NT-proBNP in the screening and diagnosis of SSc-PAH has been the lack of sufficiently high sensitivity as a 'stand-alone' test", note researcher Mandana Nikpour (The University of Melbourne, Victoria, Australia) and colleagues.

The team found that ADMA levels, measured using high performance liquid chromatography, were significantly higher among 15 SSc patients with newly diagnosed PAH who had not received treatment than 30 SSc patients without PAH, at an average of 0.76 µM versus 0.59 µM.

ADMA levels remained significantly associated with PAH after individually taking into account specific disease characteristics, cardiovascular risk factors and other SSc-related vascular complications, with odds ratios ranging from 1.14 to 1.19.

Using a cutoff point of 0.7 µM, the researchers were able to identify PAH with 86.7% sensitivity and 90.0% specificity and an accuracy of 86%.

But noting that "a high sensitivity is crucial in screening for SSc-PAH," they combined their ADMA screening model with the biomarker NT-proBNP at or above 210 ng/mL and improved sensitivity to 100% without reducing specificity.

"This has important clinical implications as non-invasive, biomarker-based screening models may enable the convenient and accurate identification of SSc patients who require further diagnostic evaluation for the presence of PAH", say Nikpour and colleagues in Clinical and Experimental Rheumatology.

Right heart catheterisation is necessary for making a definitive diagnosis of SSc-PAH but being invasive it is not feasible for general screening, they note.

Serum ADMA levels did not correlate with right heart catheterisation haemodynamics, due to largely remaining below the 10 µM necessary to directly affect nitric oxide production. The researchers suggest that they are therefore likely to be a surrogate marker of intracellular changes in methylarginine metabolism, reflecting greater changes in intracellular ADMA concentrations.

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