Srinivasan Beddhu1,2, Robert E Boucher3, Jie Sun4, Niranjan Balu4, Michel Chonchol5, Sankar Navaneethan6,7, Glenn M Chertow8, Raymond Townsend9, William Haley10, Alfred K Cheung11,3, Molly B Conroy12, Dominic S Raj13, Dongxiang Xu4, Thomas George14, Reem Yunis8, Guo Wei3, Gador Canton4, Jeffrey Bates15,16, Jing Chen17, Vasilios Papademetriou18, Henry Punzi19, Alan Wiggers20, Jackson T Wright20, Tom Greene21, Chun Yuan4. 1. Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, USA. Srinivasan.beddhu@hsc.utah.edu. 2. Division of Nephrology & Hypertension, University of Utah School of Medicine, 85 North Medical Drive East, Room 201, Salt Lake City, UT, 84112, USA. Srinivasan.beddhu@hsc.utah.edu. 3. Division of Nephrology & Hypertension, University of Utah School of Medicine, 85 North Medical Drive East, Room 201, Salt Lake City, UT, 84112, USA. 4. Department of Radiology, Vascular Imaging Lab, University of Washington, Seattle, WA, USA. 5. Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 6. Section of Nephrology, Baylor College of Medicine, Houston, TX, USA. 7. Section of Nephrology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA. 8. Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA, USA. 9. Division of Nephrology, University of Pennsylvania, Philadelphia, PA, USA. 10. Division of Nephrology, Mayo Clinic, Jacksonville, FL, USA. 11. Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, USA. 12. Division of General Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. 13. Division of Nephrology, George Washington University, Washington, DC, USA. 14. Division of Nephrology, Cleveland Clinic, Cleveland, OH, USA. 15. Medical Care Line, Michael E. DeBakey VA Medical Center, Houston, TX, USA. 16. Department of Medicine, Baylor College of Medicine, Houston, TX, USA. 17. Tulane University School of Medicine, New Orleans, LA, USA. 18. Veterans Affairs Medical Center, Washington, DC, USA. 19. Department of Medicine & Clinical Research, Punzi Medical Center, Carrollton, TX, USA. 20. Division of Nephrology and Hypertension, Case Western Reserve University, Cleveland, OH, USA. 21. Division of Biostatistics, University of Utah School of Medicine, Salt Lake City, UT, USA.
Abstract
BACKGROUND: It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in CKD. The objectives of this study were to 1. Characterize the associations of CKD with presence and morphology of atherosclerotic plaques on carotid magnetic resonance imaging (MRI) and 2. Examine the associations of baseline CKD and carotid atherosclerotic plaques with subsequent cardiovascular events. METHODS: In a subgroup (N = 465) of Systolic Blood Pressure Intervention Trial. (SPRINT) participants, we measured carotid plaque presence and morphology at baseline and after 30-months with MRI. We examined the associations of CKD (baseline eGFR < 60 ml/min/1.73m2) with progression of carotid plaques and the SPRINT cardiovascular endpoint. RESULTS: One hundred and ninety six (42%) participants had CKD. Baseline eGFR in the non-CKD and CKD subgroups were 77 ± 14 and 49 ± 8 ml/min/1.73 m2, respectively. Lipid rich necrotic-core plaque was present in 137 (29.5%) participants. In 323 participants with both baseline and follow-up MRI measurements of maximum wall thickness, CKD was not associated with progression of maximum wall thickness (OR 0.62, 95% CI 0.36 to 1.07, p = 0.082). In 96 participants with necrotic core plaque at baseline and with a valid follow-up MRI, CKD was associated with lower odds of progression of necrotic core plaque (OR 0.41, 95% CI 0.17 to 0.95, p = 0.039). There were 28 cardiovascular events over 1764 person-years of follow-up. In separate Cox models, necrotic core plaque (HR 2.59, 95% CI 1.15 to 5.85) but not plaque defined by maximum wall thickness or presence of a plaque component (HR 1.79, 95% CI 0.73 to 4.43) was associated with cardiovascular events. Independent of necrotic core plaque, CKD (HR 3.35, 95% CI 1.40 to 7.99) was associated with cardiovascular events. CONCLUSIONS: Presence of necrotic core in carotid plaque rather than the presence of plaque per se was associated with increased risk of cardiovascular events. We did not find CKD to be associated with faster progression of necrotic core plaques, although both were independently associated with cardiovascular events. Thus, CKD may contribute to cardiovascular disease principally via mechanisms other than atherosclerosis such as arterial media calcification or stiffening. TRIAL REGISTRATION: NCT01475747 , registered on November 21, 2011.
BACKGROUND: It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in CKD. The objectives of this study were to 1. Characterize the associations of CKD with presence and morphology of atherosclerotic plaques on carotid magnetic resonance imaging (MRI) and 2. Examine the associations of baseline CKD and carotid atherosclerotic plaques with subsequent cardiovascular events. METHODS: In a subgroup (N = 465) of Systolic Blood Pressure Intervention Trial. (SPRINT) participants, we measured carotid plaque presence and morphology at baseline and after 30-months with MRI. We examined the associations of CKD (baseline eGFR < 60 ml/min/1.73m2) with progression of carotid plaques and the SPRINT cardiovascular endpoint. RESULTS: One hundred and ninety six (42%) participants had CKD. Baseline eGFR in the non-CKD and CKD subgroups were 77 ± 14 and 49 ± 8 ml/min/1.73 m2, respectively. Lipid rich necrotic-core plaque was present in 137 (29.5%) participants. In 323 participants with both baseline and follow-up MRI measurements of maximum wall thickness, CKD was not associated with progression of maximum wall thickness (OR 0.62, 95% CI 0.36 to 1.07, p = 0.082). In 96 participants with necrotic core plaque at baseline and with a valid follow-up MRI, CKD was associated with lower odds of progression of necrotic core plaque (OR 0.41, 95% CI 0.17 to 0.95, p = 0.039). There were 28 cardiovascular events over 1764 person-years of follow-up. In separate Cox models, necrotic core plaque (HR 2.59, 95% CI 1.15 to 5.85) but not plaque defined by maximum wall thickness or presence of a plaque component (HR 1.79, 95% CI 0.73 to 4.43) was associated with cardiovascular events. Independent of necrotic core plaque, CKD (HR 3.35, 95% CI 1.40 to 7.99) was associated with cardiovascular events. CONCLUSIONS: Presence of necrotic core in carotid plaque rather than the presence of plaque per se was associated with increased risk of cardiovascular events. We did not find CKD to be associated with faster progression of necrotic core plaques, although both were independently associated with cardiovascular events. Thus, CKD may contribute to cardiovascular disease principally via mechanisms other than atherosclerosis such as arterial media calcification or stiffening. TRIAL REGISTRATION: NCT01475747 , registered on November 21, 2011.
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