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

• Published in: Frontiers in medicine 2024-11, Vol.11, p.1446268
• Main Authors: Heilmeier, Ursula, Feldmann, Daria, Leynes, Andrew, Seng, Magdalena, Jandova, Ilona, Keute, Marius, Kollert, Florian, Voll, Reinhard Edmund, Finzel, Stephanie
• Format: Article
• Language: English
• Subjects: arteriosclerotic cardiovascular risk; carotid ultorasonography; CRP; Framingham score; inflammatory systemic sclerosis; Medicine; systemic sclerosis
• ISSN: 2296-858X; 2296-858X
• DOI: 10.3389/fmed.2024.1446268

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. Sixty-five SSc patients were recruited and assigned to the CRP+ SSc group (  = 20) if their CRP levels were > 5 mg/L in at least three half-yearly visits within 2 years before enrolment or to the CRP- SSc group (  = 45), respectively. All patients underwent an anamnesis, physical examination, blood draw, and bilateral carotid ultrasound in order to assess arteriosclerotic burden including the presence, number and height of plaques, and carotid intima-media thickness (CIMT) as well as lipid profiles. 10-year ASCVD risk was estimated via the ASCVD risk estimator plus. Statistical evaluation included Spearman's correlations, logistic regression and random forest modeling under 5-fold cross-validation, and permutation testing to determine combinations of cardiovascular variables highly discriminatory for CRP-positivity. 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 ≤   ≤ 0.017) and a significantly higher 10-year ASCVD risk (  = 0.047), relative to CRP- SSc patients. Additionally, within the subgroup of CRP+ SSc patients, positive correlations between CRP levels and CIMT right (