Risk Stratification in Dialysis Patients: Coronary Artery Calcification Score Combined with High Sensitive C-Reactive Protein and Framingham Score for Cardiovascular Risk Prediction in Asymptomatic Subjects

Abstract

Introduction: Vascular calcification independently predicts cardiovascular disease, the major cause of death in Chronic Kidney Disease (CKD) patients. Coronary Artery Calcium Score (CACS) is a marker for atherosclerotic plaque burden, vascular calcification and has been shown to be a predictor of incidence of myocardial infarction and death from Cardiovascular (CV) disease. Objectives: The aim of the study was to evaluate factors influencing CV mortality in a group of Peritoneal Dialysis (PD) patients during a six year observation period. Patients and methods: The study included 53 patients with no symptoms of CV disease (25 women, 28 men; mean age of 52 ± 12 years) treated with PD for a median period of 24 months. Baseline Framingham Risk Score (FRS) was assessed and CACS was measured using Multi-Row Spiral Computed Tomography (MSCT). Laboratory measurements included high sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG), fibroblast growth factor 23 (FGF23), osteopontin (OPN), osteocalcin (OC), intact parathyroid hormone (iPTH), total calcium (Ca) and phosphates (Pi). The data concerning mortality was collected over a 6 year period. Results: During the six year observation period, 24 (45%) patients died, including 19 due to CV causes. Median overall survival was 72 months (lower quartile, 17 months). CACS was a significant predictor of all-cause and CV mortality both in simple analysis (HR=1.03 per 100 Agatston units, p=0.02 and HR=1.05, p=0.003), as well as in a multiple model adjusted for age of patients, dialysis duration, weekly creatinine clearance, Ca x Pi, iPTH, OPG, hsCRP and FRS (HR=1.04, p=0.02 and HR=1.05, p=0.01). The value of 800 Agatston units significantly differentiated the group into those with higher and lower risk for CV death (p=0.04). Age and FGF23 concentration were independent predictors of CACS. Also, hsCRP and FRS significantly predicted all-cause and CV mortality in simple Cox regression (HR=1.04, p=0.002 and HR=1.04, p=0.003; HR=1.14, p=0.047 and HR=1.23, p=0.01) as well as in a multiple model (HR=1.05, p=0.002 and HR=1.05, p=0.01; HR=1.23, p=0.01 and HR=1.33, p=0.004). Adding CACS to FRS and hsCRP significantly improved the prediction of cardiovascular mortality (p=0.02). Conclusions: Coronary calcium imaging is a non-invasive method of CV risk stratification that can accurately identify high-risk asymptomatic dialysis patients at the start of dialysis. The assessment of CACS together with inflammatory markers and conventional CV risk factors (FRS) may contribute to early diagnosis, prevention and reduction of deaths from CV disease in dialysis patients. Among the markers of bone disease, FGF-23 (a regulator of phosphorus metabolism) may be an early predictor of vascular calcification among dialysis patients.