Abstract

BackgroundIt 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.MethodsIn 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.ResultsOne 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.ConclusionsPresence 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 RegistrationNCT01475747, registered on November 21, 2011.

Highlights

  • It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in chronic kidney disease (CKD)

  • We did not find CKD to be associated with faster progression of necrotic core plaques, both were independently associated with cardiovascular events

  • CKD may contribute to cardiovascular disease principally via mechanisms other than atherosclerosis such as arterial media calcification or stiffening

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Summary

Introduction

It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in CKD. Some studies suggest greater prevalence of atherosclerotic burden as assessed by carotid and/or femoral ultrasound, in persons on chronic maintenance hemodialysis [6, 7] and to a lesser extent in non-dialysis dependent CKD [8,9,10]. Some longitudinal studies have not shown faster progression of atheroma defined by intima-media thickness measured with ultrasound in persons with CKD [11,12,13]. This issue raises the possibility that CKD might not be associated with progression of intima-media thickness on ultrasound but still associated with altered plaque characteristics predictive of increased CV risk

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