Subclinical fluid overload is significantly associated with coronary artery calcification in patients with chronic kidney disease

Abstract

Background: Cardiovascular (CV) disease is prevalent and most common cause of mortality in dialysis patients. Extracellular fluid (ECF) excess is frequently observed and an independent predictor of CV morbidity in patients with advanced chronic kidney disease (CKD). However, there are few studies about the relationship between fluid excess and CV risks even in patients with early stage CKD. The aim of present study is to investigate the association between extracellular fluid (ECF) status measured using bioelectrical impedance analysis and coronary artery calcification score (CACS) as a surrogate for CV disease in CKD patients with relatively preserved renal function. Method: Data were retrieved from the prospective observational cohort of Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (NCT02003781). Extracellular water (ECW) and total body water (TBW) were assessed by bioelectrical impedance analysis and CACS was measured by multidetector computed tomography. After exclusion of patients with significant volume overload (ECW/TBW >0.4) and substantially impaired renal function (eGFR <45.0 mLmin-11.73 m-2), patients were divided into four groups according to the quartiles of their ECW-to-TBW ratio (ECW/TBW). Coronary artery calcification (CAC) was defined as CACS more than 400 agatston units. Result: A total of 1481 patients was analyzed and the mean was 59.8 ± 11.3 years; 759 (51.2%) were men; and the mean eGFR was 85.0 ± 16.9 mLmin-11.73 m-2. The patients in the increasing quartiles of the ECW/TBW showed older, higher blood pressure, and much prevalent co-morbid conditions such as diabetes compared to those in lower quartiles. CACS [1st to 4th quartile; 0.0 (0.0 – 73.9), 9.95 (0.0 – 133.3), 12.3 (0.0 – 144.6), vs. 59.6 (0.0 – 307.3), P for trend <0.001] and CAC [1st to 4th quartile; 23 (6.2%), 36 (9.7%), 44 (12.0%), vs. 76 (20.5%), P for trend <0.001] significantly increased in accordance with increasing ECW/TBW quartiles. ECW/TBW showed an independent association with CAC after adjustment for multiple confounders (per 0.01 increase in ECW/TBW; odds ratio 2.890, 95% confidence interval 1.787 – 4.674, P <0.001). In receiver operating characteristic (ROC) analyses, the area under the ROC curve (AUC) for CAC risk prediction was significantly increased by adding ECW/TBW to a model consisting of traditional (AUC; 0.784 vs. 0.736, P = 0.013) or non-traditional factors (AUC; 0.784 vs. 0.749, P = 0.038). Conclusion: In conclusion, subclinical fluid excess in CKD patients with preserved renal function was associated with the increasing risk of CAC. This result suggests that the assessment of ECF can help to determine CV risk in patients with early stage CKD.