Association of mineral metabolism with an increase in cellular adhesion molecules: Another link to cardiovascular risk in maintenance haemodialysis?

Background. Abnormal mineral metabolism is associated with increased cardiovascular morbidity and mortality. The exact pathogenesis linking mineral metabolism to cardiovascular risk is unknown. This study was undertaken to investigate the association between serum phosphate an/or Ca × PO₄ product with serum levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 and the degree of carotid artery atherosclerosis in patients on haemodialysis. Methods. Seventy-three patients (46 male, 27 female; mean age 48±13 years, on haemodialysis for 82±80 months) were included in the study. All patients were stable, had no evidence of vascular disease and/or active infection. Consecutive 6 months clinical and laboratory data were obtained for each patient from their medical records and mean values were used for analysis. Serum levels of soluble adhesion molecules were assayed by ELISA. All subjects underwent a detailed evaluation of the carotid arteries. Results. The percentage of patients who met all three targets of NKF-K/ DOQI for phosphate, calcium and Ca × PO₄ product was 27.1%, whereas those who did not achieve the target in one, two or three parameters was 28.1, 17.7 and 14.6%, respectively. The sICAM-1 levels were significantly higher in patients who had hyperphosphataemia (serum phosphate >5.5 mg/dl; P = 0.044 and hypercalcaemia (serum calcium >9.5 mg/dl; P-0.014) both sE-selectin and sICAM-1 levels were significantly higher in patients with Ca × PO₄ product levels above 55 mg²/dl² (P = 0.002 and P = 0.000, respectively). Soluble E-selectin and sICAM levels demonstrated a near-linear increase in parallel to the degree of deviation from mineral metabolism targets. Soluble E-selectin and sICAM levels were correlated with serum phosphate and Ca × PO₄ product, but there were no correlations between adhesion molecules and carotid measurements. Conclusion. These findings suggest that in stable haemodialysis patients abnormal bone mineral metabolism was associated with increased soluble adhesion molecules. These alterations in adhesion molecules may favour the development of cardiovascular changes and contribute to high cardiovascular morbidity and mortality in patients with abnormal mineral metabolism.