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Atrial natriuretic peptide predicts disease progression and digital ulcers development in systemic sclerosis patients

Romaniello, Antonellaa; Rubattu, Speranzab,c; Gigante, Antoniettad; Simonelli, Francescab; Grimaldi, Maria C.b; D’Angelo, Adrianob; Alunni, Daniloe; Sada, Lidiab; Gasperini, Maria L.d; Marchitti, Simonac; Volpe, Massimob,c; Rosato, Edoardod

Journal of Cardiovascular Medicine: November 2019 - Volume 20 - Issue 11 - p 771–779
doi: 10.2459/JCM.0000000000000852
Research articles: Biomarkers

Aims Systemic sclerosis (SSc) is an autoimmune disease characterized by micro/macrovascular damage due to the underlying fibrosis. Markers able to predict the progression of cardiovascular damage, including digital ulcers, in SSc are warranted. We aimed at characterizing the relevance of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide plasma levels in relation to cardiovascular damage and digital ulcers in a cohort of Italian SSc patients.

Methods Seventy patients were enrolled (64 women and six men; mean age 56.7 ± 14 years) with a disease duration of 11.1 ± 8.3 years. Clinical, instrumental (nailfold videocapillaroscopy, ECG, transthoracic echocardiography, pulmonary function test with diffusion lung CO), NT-proANP and N-terminal probrain natriuretic peptide plasma levels measurement were performed at baseline. The clinical follow-up lasted 24 months. The statistical approach used to achieve the study objectives included multivariate analysis, receiver operating characteristic curve, Kaplan–Meier and Cox regression analyses.

Results Both NT-proNPs levels correlated with systolic pulmonary arterial pressure, but only the NT-proANP level correlated with right heart dimension. Both NT-proNPs levels were higher in patients experiencing events at follow-up but only the NT-proANP level significantly predicted the progression of cardiovascular damage, including development of pulmonary arterial hypertension (PAH). NT-proANP levels were higher in patients with digital ulcers and strongly predicted their development.

Conclusion Our results show that the NT-proANP plasma level significantly correlates with disease progression such as new onset of PAH, worsening of pulmonary hypertension and development of digital ulcers in a cohort of SSc Italian patients. If future studies will confirm our findings, the plasma NT-proANP level could be used in clinical practice as a novel sensitive marker for PAH and digital ulcers development in SSc.

aDivision of Cardiology, Azienda Ospedaliera Sant’Andrea

bDepartment of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Rome

cIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Neuromed, Pozzilli

dDepartment of Translational and Precision Medicine

eDepartment of Statistical Science, Sapienza University of Rome, Rome, Italy

Correspondence to Edoardo Rosato, MD, PhD, Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell’Università 37, 00185 Rome, Italy Tel: +39 06 49972040; fax: +39 0649972072; e-mail:

Received 5 February, 2019

Revised 30 May, 2019

Accepted 13 July, 2019

© 2019 Italian Federation of Cardiology. All rights reserved.