Carotid plaque thickness predicts cardiovascular events and death in patients with chronic kidney disease

Abstract Background and Aims Classical risk scoring systems highly underestimate the elevated risk of cardiovascular (CV) disease in chronic kidney disease (CKD) (1). Coronary artery calcification score (CACS) has improved prediction of CV events in patients with CKD (2). Recently, ultrasound examination of the carotid arteries with measurement of maximal carotid plaque thickness (cPTmax) has demonstrated similar predictive value as CACS in the general population (3). This is the first study to investigate whether cPTmax can predict CV events in patients with CKD. We also compared the predictive value of cPTmax and CACS. Method Two hundred patients with CKD stage 3 from the Copenhagen CKD Cohort underwent ultrasound scanning of the carotid arteries in 2016 to 2017. The assessment consisted of finding areas with plaque, if there were any, and measuring the thickest part of the plaque, cPTmax, defined as the radial distance from the media–adventitia interface to the intima–lumen interface towards the center of the arterial lumen. For the statistical analysis only the anatomical side with the highest cPTmax was used. The intra-observer coefficient of variation was 9%. Based on the distribution of cPTmax, the subjects were divided into 3 groups: No plaques, cPTmax 1.0-1.9 mm and cPTmax > 1.9 mm (the median cPTmax in the group was 1.9 mm). One hundred and seventy-five of the patients underwent a non-contrast CT scan of the coronary arteries, which was used to measure CACS. The patients were divided into the following categories: no calcification, CACS = 1-100, CACS = 101-400 and CACS > 400. The follow-up time was time elapsed from the ultrasound scan and until a predefined end-date or the time of first event, which was defined as a composite of major CV events or death of any cause (MACE). CV events included: myocardial infarction, percutaneous coronary intervention, coronary bypass surgery, ischemic stroke, carotid endarterectomy or stenting, non-traumatic lower limb amputation, lower limb artery bypass graft, percutaneous transluminal angioplasty of a lower limb. Results The average follow-up time was 5.4 years. Twenty patients (10%) experienced a CV event and 28 patients died (14%). In a crude absolute risk plot (Figure), patients with no plaque at baseline showed the lowest risk of MACE, whereas patients with cPTmax 1.0-1.9 mm showed an intermediate risk, and patients with cPTmax >1.9 mm the highest risk (log rank test, p<0.0001). When using the group of patients with no plaque as the reference in an unadjusted Cox-regression analysis, the hazard ratio (HR) of MACE was significantly increased in patients with cPTmax = 1.0-1.9 mm (HR = 3.8 (CI: 1.5 - 9.9), p<0.01) and in patients with cPTmax >1.9 mm (HR = 8.4 (CI: 3.4 – 20.8), p<0.0001). After adjustment for age, sex, diabetes, smoking, hypertension, and hypercholesterolemia, only patients with cPTmax >1.9 mm showed a significantly increased HR of MACE (HR 3.2, CI 1.1-9.3), p<0.05. We applied C-statistics to assess which imaging technique had the best predictive value of MACE in this cohort. The differences in C-statistics were similar for the two imaging methods: cPTmax (0.21, p < 0.0001) and CACS (0.21, p < 0.0001). Conclusion Our results indicate that measurement of cPTmax may be a useful method for prediction of MACE in CKD. In the present small study, cPTmax and CACS showed equal potential for predicting MACE Ultrasound imaging is more convenient, more widely available, and without radiation exposure. To further assess the value of cPTmax in predicting CV risk in CKD, a larger study of patients with all CKD stages is needed.