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Impaired kidney function is associated with intraplaque hemorrhage in patients undergoing carotid endarterectomy
Marian Wesseling1, Ian D van Koeverden1, Guus W van Lammeren2
1Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Insights
Reduced kidney function in patients undergoing carotid endarterectomy is linked to plaque hemorrhage and fibrous-atheromatous plaques, not inflammation. This suggests non-inflammatory pathways contribute to plaque vulnerability in kidney disease.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Pathology
Background:
- Moderate to poor kidney function increases atherosclerotic event risk.
- Vascular inflammation is implicated in chronic kidney disease (CKD) atherogenesis.
- The link between kidney function and atherosclerotic plaque composition is underexplored.
Purpose of the Study:
- To investigate the association between kidney function and atherosclerotic plaque composition in patients undergoing carotid endarterectomy.
Main Methods:
- Immunohistochemical analysis of 1796 carotid endarterectomy plaques for macrophages, smooth muscle cells, calcifications, collagen, microvessels, lipid core, and hemorrhage.
- Measurement of intraplaque and plasma cytokines.
- Quantitative proteomics on 40 carotid plaques.
Main Results:
- Decreased kidney function correlated with increased odds of intraplaque hemorrhage (OR 1.15) and fibrous-atheromatous plaques (OR 1.21) per 20-point eGFR decrease.
- Proteomics indicated decreased kidney function was associated with upregulated complement and coagulation pathways.
Conclusions:
- Decreased kidney function is associated with carotid plaque hemorrhage but not inflammatory markers.
- Non-inflammatory pathways, such as complement and coagulation, may drive plaque vulnerability in patients with reduced kidney function.
Background And Aims:
Previously, we showed that patients undergoing carotid endarterectomy have an increased risk for major atherosclerotic events in the presence of moderate or poor kidney function. Acceleration of vascular inflammatory responses is considered to be causally involved in progression of atherogenesis and poor outcome in chronic kidney disease patients. The association between kidney function and plaque composition has not been thoroughly investigated yet. The aim of this study was to investigate the association between kidney function and atherosclerotic plaque composition in patients undergoing carotid endarterectomy.
Methods:
Atherosclerotic plaques, harvested from 1796 patients who underwent carotid endarterectomy, were immunohistochemically stained for macrophages, smooth muscle cells, calcifications, collagen, microvessels, lipid core size and intraplaque hemorrhage. Cytokines were measured in plaque and plasma and associated with kidney function. Quantitative proteomics were performed on 40 carotid plaques and associated with kidney function.
Results:
Decreased kidney function was associated with increased odds ratio of intraplaque hemorrhage, OR 1.15 (95% CI; 1.02-1.29 (p = 0.024)) and increased odds ratio of fibrous-atheromatous plaques (plaques with lipid core presenting more than 10% of total plaque surface) OR 1.21 (95% CI; 1.07-1.38 (p = 0.003)) per decrease of 20 points in eGFR. Proteomics revealed that decreased kidney function was associated with upregulation of the classical pathway of the complement system and the intrinsic pathway of the coagulation system.
Conclusions:
Decreased kidney function was associated with plaque hemorrhage but not with inflammatory plaque characteristics. Our data suggests that other pathways than the inflammation-pathway are involved in plaque vulnerability and poor outcome in patients with decreased kidney function.