Copeptin may be useful as a biomarker of microcirculatory changes in patients with systemic sclerosis (SSc), according to a study published in Clinical, Cosmetic and Investigational Dermatology. 

Although tissue fibrosis is a primary characteristic of systemic sclerosis, vascular damage is also significant in that it drives much of its pathophysiology. Vascular damage is most prominent when it causes clear microcirculatory changes, such as Raynaud’s phenomenon or refractory ischemic digital ulcers, both conditions that are often painful and disabling. 

Hence, there is an urgency in the research community to discover an effective therapeutic solution for vasculopathy in SSc. To achieve this end, scientists have focused on vasopressin, a vasoactive peptide that may play a role in vasoconstriction, inflammation, and fibrosis. Specifically, there is considerable interest in copeptin, the C-terminal part of provasopressin that may be useful in assessing vasopressinergic system activity. 

“Despite recent advances in systemic sclerosis treatment, it is still challenging to identify patients at risk of rapid disease progression and development of severe organ complications,” the authors of the study wrote. “There is an urgent need to identify potential biomarkers of incipient vasculopathy before tissue damage becomes clinically apparent and irreversible.” 

Read more about SSc etiology 

The authors sought to investigate the suitability of copeptin as a biomarker of peripheral microvasculopathy in SSc. They enrolled a cohort of consecutive patients between September 2019 and May 2022 who were diagnosed with SSc at a tertiary referral center in Warsaw, Poland. They also recruited age- and sex-matched healthy volunteers as controls. 

The research team performed an extensive evaluation of skin and lung disease in the recruited patients. The patients were also assessed for manifestations of microcirculatory disease, such as Raynaud’s phenomenon. Patients were further subject to examinations investigating the extent of muscular, joint, and gastrointestinal involvement. The research team measured serum copeptin concentrations at baseline and at various points in the trial. 

Thirty-seven individuals with SSc were selected for this study. The main finding was that copeptin levels significantly correlated with microcirculatory dysfunction, and that changes of serum copeptin concentration were reflective of changes to vasopressinergic system activity. 

“Further prospective studies on larger cohorts of patients with evaluation of how different vascular therapies impact copeptin concentration are needed before its measurements may be used in clinical practice,” the authors concluded. 


Maciejewska M, Stec A, Zaremba M, Maciejewski C, Rudnicka L, Sikora M. Copeptin as a biomarker of microcirculation alterations in systemic sclerosisClin Cosmet Investig Dermatol. Published online May 25, 2023. doi:10.2147/CCID.S409490