Coronary Calcifications in End-Stage Renal Disease Patients: A New Link between Osteoprotegerin, Diabetes and Body Mass Index?

Abstract

The aim of the study was to assess the factors potentially involved in coronary artery calcifications (CAC) in end-stage renal disease patients. 253 hemodialysis (HD) patients (92 females, 161 males), aged 62.5 ± 13.5, who had been on HD treatment for at least 6 months, were enrolled in a cross-sectional study. Calcium-phosphate product (Ca × P), body mass index (BMI), fetuin-A, osteoprotegerin (OPG), osteopontin, transforming growth factor-β1 (TGF-β1), fibroblast growth factor-23 (FGF-23) and matrix Gla protein (MGP) were considered. CAC was assessed using multislice spiral computed tomography and calcium score was quantified by means of the Agatston score. The median calcium score was 364 Agatston (range 0–7,336). CAC was detected in 228/253 patients (90.1%). Multivariate regression analysis, adjusted for age and for dialysis vintage, showed that TGF-β1, OPG and days with Ca × P >55 mg/dl are independent predictors of CAC, while MGP was shown to be a protective factor. Surprisingly, results showed that BMI was a protective factor too: the interpolation with cubic spline function revealed a significant reduction in calcium score in patients with a high BMI (>28). However, when diabetes was considered in the regression analysis, only OPG emerged as a predictor of a high CAC score. The interpolation with spline function continued to show a significant reduction in CAC score in nondiabetic and in diabetic patients with the highest BMI quartile. The protective effect of a high BMI on CAC might represent another example of inverse biology in dialysis patients but it needs to be further addressed in larger longitudinal studies.

Dephosphorylated-uncarboxylated Matrix Gla protein concentration is predictive of vitamin K status and is correlated with vascular calcification in a cohort of hemodialysis patients

“…Because MGP is a potent inhibitor of vascular calcifications [1, 2, 4], some authors have suggested that the protein may be useful in the monitoring or even the detection of vascular calcifications in CKD or HD subjects [25, 35]. In the present study, we confirmed a significant correlation between dp-ucMGP levels and the calcification score in the univariate analysis and this association was confirmed in the multivariate model.…”

“…This positive correlation between dp-ucMGP levels and the calcification score supports however the theoretical role of MGP in the development of vascular calcifications. It also advocates the need for additional studies, particularly with other active isoforms of MGP [7, 22, 32, 35–39]. For instance, total uncarboxylated MGP (which may be partially bioactive) has been negatively associated with coronary calcification in dialysis patients [36].…”

Relationship of Fibroblast Growth Factor 23 with Left Ventricle Mass Index and Coronary Calcificaton in Chronic Renal Disease

“…In contrast, calcium score was inversely correlated with FGF-23 and BMI. FGF-23 showed a signi�icant inverse correlation with CAC in univariate analysis but it was not an independent predictive factor of CAC in multivariate analysis [30]. Conversely, Roos et al [31] reported no association between CAC and FGF-23 levels in patients with normal kidney function.…”

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

“…Since calcium and phosphorus are each raised above adult normal values, fetal blood has a high calcium x phosphorus product (Ca x P) that may facilitate spontaneous calcium-phosphate crystals to form and cause soft tissue calcifications. In adults, a Ca x P value Ͼ5.6 mmol 2 /l 2 or 70 mg 2 /dl 2 is associated with calciphylaxis, coronary artery calcifications, and increased mortality (58,115,126,724). However, this level may be needed to mineralize the fetal skeleton and may be nonhazardous in utero due to its relatively short duration.…”