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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Plasma Complement Protein C3a Level Was Associated with Abdominal Aortic Calcification in Patients on Hemodialysis
Yaqin Wang1,2,3,4, Yuanyi Miao1,2,3,4, Kunjing Gong1,2,3,4
1Renal Division, Department of internal Medicine, Peking University First Hospital, Beijing, 100034, China.
Insights
Complement system activation is linked to cardiovascular disease in hemodialysis patients. Higher C3a levels are independently associated with severe abdominal aortic calcification (AAC), suggesting C3a may help diagnose this condition.
Area of Science:
- Nephrology
- Immunology
- Cardiovascular Medicine
Background:
- Cardiovascular disease (CVD) is a major complication in hemodialysis (HD) patients.
- Vascular calcification, particularly abdominal aortic calcification (AAC), significantly contributes to CVD morbidity and mortality in this population.
- The role of the complement system in the pathogenesis of vascular calcification in HD patients requires further elucidation.
Purpose of the Study:
- To investigate the relationship between complement activation markers and the presence and severity of abdominal aortic calcification (AAC) in patients undergoing hemodialysis.
- To determine if specific complement components are associated with vascular calcification in this cohort.
- To explore the potential diagnostic value of complement activation products for severe AAC.
Main Methods:
- Prospective study involving 108 hemodialysis patients and 65 healthy controls.
- Measurement of plasma complement components including C3a, C5a, mannose-binding lectin (MBL), membrane attack complex (MAC), C3c, factor B (fB), factor H (fH), C1q, and C4.
- Quantification of abdominal aortic calcification (AAC) using plain abdominal radiography and calculation of AAC scores.
- Statistical analyses including correlation, logistic regression, and ROC curve analysis to assess associations between complement levels and AAC severity.
Main Results:
- Hemodialysis patients exhibited increased levels of MBL and C5a, and decreased levels of C3c and fB compared to controls.
- Plasma C3a levels were significantly correlated with AAC scores (r=0.461, p=0.002).
- Higher C3a levels were independently associated with severe AAC (OR, 6.28; p=0.03) after adjusting for age, sex, and calcium levels. The AUC for C3a in diagnosing severe AAC was 0.75.
Conclusions:
- The complement system is activated in patients undergoing hemodialysis.
- Elevated plasma C3a levels are a significant independent predictor of severe abdominal aortic calcification in HD patients.
- Plasma C3a may serve as a valuable biomarker for diagnosing severe AAC in hemodialysis patients.
Abstract:
The complement system plays an important role in cardiovascular disease in patients on hemodialysis. Vascular calcification is also one of the major causes of cardiovascular disease. We want to investigate the relationship between complement activation and vascular calcification in dialyzed patients. One hundred eight hemodialysis patients and 65 heathy controls were enrolled prospectively. Plasma C3a, C5a, mannose-binding lectin (MBL), and membrane attack complex (MAC or C5b-9) levels were detected using ELISA. Plasma C3c, fB, fH, C1q, and C4 levels were measured by immunity transmission turbidity. Abdominal aortic calcification (AAC) was measured by abdomen lateral plain radiograph, and the AAC score was calculated. We identified increased level of MBL and decreased level of C3c and complement factor B compared with normal control. However, C1q, complement factor H, and C4 levels remained at a similar level compared with individuals with normal renal function. The C3a and C5a levels increased, without change of MAC. Forty two of 108 HD patients had the AAC score. C3a levels were correlated with AAC score (r = 0.461, p = 0.002). The median C3a concentration was 238.72 (196.96, 323.41) ng/mL. When evaluated as AAC categories (≤ 4, > 5) with ordinal logistic regression, univariate analyses revealed that higher C3a levels were associated with severe AAC, while multivariate analyses adjusted for age, sex, and calcium level showed that higher C3a levels (OR, 6.28 (1.25-31.69); p = 0.03) were associated with severe AAC. The areas under the curve (AUC) for C3a to diagnose severe abdominal aortic calcification were 0.75(0.58-0.92, 0.01). The complement system was activated in patients on hemodialysis. Higher C3a levels are independently associated with severe AAC. Plasma C3a might have a diagnostic value for the severe AAC in HD patients.
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