Associations of epicardial fat with coronary calcification, insulin resistance, inflammation, and fibroblast growth factor-23 in stage 3-5 chronic kidney disease

Abstract

BackgroundEpicardial fat, quantified in a single multi-slice computed tomography (MSCT) slice, is a reliable estimate of total epicardial fat volume (EFV). We sought to determine risk factors for EFV detected in a single-slice MSCT measurement (ssEFV) in pre-dialysis chronic kidney disease (CKD) patients. Our primary objective was to determine the association between ssEFV and coronary artery calcification (CAC).Methods94 pre-dialysis stage 3–5 CKD patients underwent MSCT to measure ssEFV and CAC. ssEFV was quantified at the level of the left main coronary artery. Measures of inflammation, traditional and kidney-related cardiovascular disease risk factors were collected.ResultsMean age: 63.7 ± 14 years, 56% male, 39% had diabetes, and mean eGFR: 25.1 ± 11.9 mL/min/1.73 m2. Mean ssEFV was 5.03 ± 2.4 cm3. By univariate analysis, body mass index (BMI) (r = 0.53; P = <0.0001), abdominal obesity (r = 0.51; P < 0.0001), high density lipoprotein (HDL) cholesterol (r = − 0.39; P = <0.0001), insulin resistance (log homeostasis model assessment of insulin resistance (log HOMA-IR)) (r = 0.38, P = 0.001), log interleukin-6 (IL-6) (r = 0.34; P = 0.001), and log urinary albumin to creatinine ratio (UACR) (r = 0.30, P = 0.004) demonstrated the strongest associations with ssEFV. Log coronary artery calcification (log CAC score) (r = 0.28, P = 0.006), and log fibroblast growth factor-23 (log FGF-23) (r = 0.23, P = 0.03) were also correlated with ssEFV. By linear regression, log CAC score (beta =0.40; 95% confidence interval (CI), 0.01-0.80; P = 0.045), increasing levels of IL-6 (beta = 0.99; 95% CI, 0.38 – 1.61; P = 0.002), abdominal obesity (beta = 1.86; 95% CI, 0.94 - 2.8; P < 0.0001), lower HDL cholesterol (beta = −2.30; 95% CI, – 3.68 to −0.83; P = 0.002) and albuminuria (log UACR, beta = 0.81; 95% CI, 0.2 to 1.4; P = 0.01) were risk factors for increased ssEFV.ConclusionsIn stage 3–5 CKD, coronary calcification and IL-6 and were predictors of ssEFV. Further studies are needed to clarify the mechanism by which epicardial fat may contribute to the pathogenesis of coronary disease, particularly in the CKD population.

Epicardial Adipose Tissue Accumulation Is Associated With Renal Dysfunction and Coronary Plaque Morphology on Multidetector Computed Tomography

“…25, 26 Kerr et al found a positive correlation between urinary albumin to creatinine ratio and single-slice EAT volume in stage 3-5 CKD patients. 25 Cordeiro et al demonstrated that increased EAT volume was a predictor for future CAD events …”

Energy Excess, Glucose Utilization, and Skeletal Remodeling: New Insights

“…Recent studies showed that the C-terminal portion of FGF-23 is positively associated with increased BMI and insulin resistance as measured by Homeostasis Model Assessment (HOMA), but negatively associated with ferritin and serum iron. (31)(32)(33)(34) Weight loss has been shown to reduce the serum levels of Another study showed that the response of FGF-23 and PTH to a phosphate load is impaired in T2D. (36) This is a new area of investigation, and more studies are needed to define the potential impact of skeletal factors besides osteocalcin on glucose tolerance in both animals and humans.…”

“…Recent studies showed that the C-terminal portion of FGF-23 is positively associated with increased BMI and insulin resistance as measured by Homeostasis Model Assessment (HOMA), but negatively associated with ferritin and serum iron. (31)(32)(33)(34) Weight loss has been shown to reduce the serum levels of FGF-23. (35) Another study showed that the response of FGF-23 and PTH to a phosphate load is impaired in T2D.…”

Epicardial adipose tissue in patients with end-stage renal disease on haemodialysis

“…Both inflammation and oxidative stress play central roles in the development of atherosclerosis in patients with CKD, and in functional CVD related outcomes, including pathogenesis of LVH, arterial stiffness and global cardiac function [12,13]. Recently the associations between increased EAT thickness, Il-6 and coronary artery calcification (CAC) in patients with CKD stage 3-5 [14] have been demonstrated. Additionally, increasing volumes of EAT in this patient population are associated with an increasing risk of cardiovascular events, independent of general adiposity, and are a better predictor of risk than abdominal visceral adipose tissue [15*].…”