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 ( = 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.
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 ≤ ≤ 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 ( = 0.657, = 0.002) and mean CIMT left and right (ρ = 0.497, = 0.026) were seen. Combined ROC models identified the four lipid components (HDL, LDL, total cholesterol, and triglycerides) or the SSc duration and ASCVD category to differentiate with high cross-validated ROC-AUCs (AUC: 0.83 ± 0.15, and AUC: 0.86 ± 0.09, 0.001) for prolonged CRP-positivity among SSc patients.
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.
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http://dx.doi.org/10.3389/fmed.2024.1446268 | DOI Listing |
Front Immunol
December 2024
Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Introduction: The critical role played by vascular dysfunction and ineffective angiogenesis in the pathophysiology of systemic sclerosis (SSc) suggests that circulating biomarkers reflecting these alterations may be useful in the clinical evaluation of this patient group. We sought to address this issue by conducting a systematic review and meta-analysis of studies investigating a such candidate biomarker, endostatin, an endogenous glycoprotein exerting anti-angiogenic effects, in SSc patients and healthy controls.
Methods: A literature search was conducted in the electronic databases Web of Science, PubMed, and Scopus from inception to 27 May 2024.
Cureus
December 2024
Department of Rheumatology, Mayo Clinic, Jacksonville, USA.
The term Raynaud's phenomenon (RP) is used to describe complex symptoms related to vascular compromise, which are typically exacerbated by cold-induced vasoconstriction, emotional stress, or other sympathomimetic factors. In almost all patients with limited cutaneous systemic sclerosis (SSc), the first symptom is RP, often two to five years before any other symptom of scleroderma. The clinical course and severity of this disease are variable and highly fatal in some individuals, which has led to the development of strategies for timely diagnosis; hence, criteria for the very early diagnosis of systemic sclerosis have been established.
View Article and Find Full Text PDFBMC Anesthesiol
January 2025
Department of Anesthesia, Surgical Intensive Care and Pain Medicine, Faculty of Medicine, Tanta University Hospitals, Tanta, Gharbya, Egypt.
Background: Although surviving sepsis campaign (SSC) guidelines are the standard for sepsis and septic shock management, outcomes are still unfavourable. Given that perfusion pressure in sepsis is heterogeneous among patients and within the same patient; we evaluated the impact of individualized hemodynamic management via the transcranial Doppler (TCD) pulsatility index (PI) on mortality and outcomes among sepsis-induced encephalopathy (SIE) patients.
Methods: In this prospective, single-center randomized controlled study, 112 patients with SIE were randomly assigned.
BMJ Open Gastroenterol
January 2025
Department of Gastroenterology, Hepatology and Transplant Medicine, University of Duisburg-Essen, Essen, Germany
Objective: Secondary sclerosing cholangitis (SSC) represents a disease with a poor prognosis increasingly diagnosed in clinical settings. Notably, SSC in critically ill patients (SSC-CIP) is the most frequent cause. Variables associated with worse prognosis remain unclear.
View Article and Find Full Text PDFCurr Cardiol Rep
January 2025
Johns Hopkins University Division of Cardiology, Baltimore, MD, USA.
Purpose Of Review: The present review aims to address systemic sclerosis (SSc)-associated myocardial disease, a significant cause of morbidity and mortality, by examining the mechanisms of inflammation, microvascular dysfunction, and fibrosis that drive cardiac involvement. The objective is to elucidate critical risk factors and explore advanced diagnostic tools for early detection, enhancing patient outcomes by identifying those at highest risk.
Recent Findings: Recent studies underscore the importance of specific autoantibody profiles, disease duration, and cardiovascular comorbidities as key risk factors for severe cardiac manifestations in SSc.
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