Chronic kidney disease, atherosclerotic plaque characteristics on carotid magnetic resonance imaging, and cardiovascular outcomes

Srinivasan Beddhu, Robert E Boucher, Jie Sun, Niranjan Balu, Michel Chonchol, Sankar Navaneethan, Glenn M Chertow, Raymond Townsend, William Haley, Alfred K Cheung, Molly B Conroy, Dominic S Raj, Dongxiang Xu, Thomas George, Reem Yunis, Guo Wei, Gador Canton, Jeffrey Bates, Jing Chen, Vasilios Papademetriou, Henry Punzi, Alan Wiggers, Jackson T Wright, Tom Greene, Chun Yuan, Srinivasan Beddhu, Robert E Boucher, Jie Sun, Niranjan Balu, Michel Chonchol, Sankar Navaneethan, Glenn M Chertow, Raymond Townsend, William Haley, Alfred K Cheung, Molly B Conroy, Dominic S Raj, Dongxiang Xu, Thomas George, Reem Yunis, Guo Wei, Gador Canton, Jeffrey Bates, Jing Chen, Vasilios Papademetriou, Henry Punzi, Alan Wiggers, Jackson T Wright, Tom Greene, Chun Yuan

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.

Keywords: Atherosclerosis; Carotid plaque; Chronic kidney disease.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1 — Fig. 1
Magnetic resonance (T1 weighted, time of flight, T2 weighted and proton-density-weighted) images of carotid plaques with a necrotic core (panel a) and calcification (panel b). * represents lumen and arrows point to lesions in common carotid artery before carotid bifurcation

Fig. 2 — Fig. 2
Baseline and longitudinal associations of CKD status with carotid plaque occurrence and plaque morphology. Panel a. Results of separate logistic regression models relating CKD status with MWT > 1.5 mm, NC+ plaque or Ca + plaque adjusted for age, gender, race, CVD history, statin use, and Framingham risk score group in all 465 participants. Panel b: Results of separate ordinal logistic regression models relating CKD status with categories of <− 20, − 20% to 20, > 20% longitudinal change in the given plaque type adjusted for age, gender, race, CVD history, statin use, Framingham risk score group and BP intervention arm, stratified by MRI site. Model 1 included all 323 participants with data, model 2 included 96 participants with NC+ plaque at baseline and model 3 included 147 participants with Ca + plaque at baseline. All models included only participants with non-missing quantitative follow-up MRI

Fig. 3 — Fig. 3
Forest plots of associations of carotid plaque and plaque morphology and CKD status with CVD outcome. Results of separate Cox regression models relating any, NC+ or Ca + plaque and CKD status with the cardiovascular composite outcome. Models were adjusted for age, gender, race, CVD history, statin use, Framingham risk score group and BP intervention arm and stratified by MRI site

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