Chronic low-grade inflammation in patients with systemic sclerosis is associated with increased risk for arteriosclerotic cardiovascular disease.

Background: Vasculopathy is a hallmark of systemic sclerosis (SSc) putting patients at an increased risk of cardiovascular disease. Approximately 20-25% of all SSc patients show prolonged elevated C-reactive protein (CRP) levels and thus signs of chronic low-grade inflammation. While CRP-positivity is an independent predictor of cardiovascular disease in non-SSc populations, the relationship between CRP-positivity and cardiovascular health/atherosclerosis in SSc patients is only incompletely understood. Here, we aimed to assess (1) which general, SSc disease-specific and cardiovascular parameters are associated with CRP-positivity in a cohort of SSc patients with prolonged CRP elevations (CRP+ SSc group) relative to SSc patients without CRP elevations (CRP- SSc group). In addition (2), we aimed to investigate whether prolonged CRP-positivity in SSc patients is associated with a higher cardiovascular risk and an increased atherosclerotic burden. We also aimed to (3) identify via random forest classification modeling which combined cardiovascular and/or SSc-specific parameters could differentiate best between SSc patients with elevated CRP levels (the so-called "inflammatory SSc subtype") and SSc patients without increased CRP levels. Methods: Sixty-five SSc patients were recruited and assigned to the CRP+ SSc group ( Results: SSc groups showed comparable mean age, height, and extent of SSc organ involvement. Regarding cardiovascular health, CRP+ SSc patients exhibited a significantly altered HDL-, LDL-, and triglyceride profile (0.001 ≤ Conclusion: Our data indicate that persistent CRP-positivity and thus chronic low-grade inflammation in SSc patients enhance the risk for arteriosclerotic-cardiovascular disease significantly beyond the ASCVD risk observed for our SSc patients without CRP elevations. It seems to be along with a disrupted lipid profile the hallmark of a distinct "inflammatory" subgroup of SSc patients. However, large population-based studies and clinical trials in patients with SSc are needed to validate our findings in a prospective or interventional setting.