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Exploration of Association of 1,25-OH2D3 with Augmentation Index, a Composite Measure of Arterial Stiffness

Jason Andrade^*,, Lee Er^,, Andrew Ignaszewski^*,, and Adeera Levin^*,,||

^* Department of Medicine, Division of Cardiology, Centre for Health Evaluation and Outcome Sciences, BC Provincial Renal Agency, and ^|| Division of Nephrology, University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia, Canada

Correspondence: Dr. A. Levin, University of British Columbia, Division of Nephrology, Saint Paul's Hospital, 1081 Burrard Street, Room 6010A, Vancouver, BC, Canada V6Z 1Y8. Phone: 604 6822344, ext. 62232; Fax: 604 8068120; E-mail: alevin{at}providencehealth.bc.ca

Background and objectives: Abnormalities in mineral metabolism [calcium, phosphate, and immunoreactive parathyroid hormone (PTH)] and vitamin D have been linked to increases in central arterial stiffness. Central arterial stiffness can be measured using noninvasive technologies, including augmentation index (AIx), a composite measure of arterial stiffness.

Design, setting, participants, and measurements: In 131 outpatients identified from individual cardiac or kidney disease clinics, we examined conventional demographic and laboratory risk factors, vitamin D levels (1,25-OH2D3 and 25-OHD3), and markers of inflammation or endothelial function [C-reactive peptide (hsCRP), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), and IL-6] in relationship to AIx.

Results: The median eGFR was significantly different between clinics (range 25–81 ml/min). Subjects with higher phosphate or MMP-9 levels were found to have a higher AIx (P = 0.02 and 0.07, respectively). Lower 1,25-OH2D3 levels or reduced eGFR were associated with higher AIx (P = 0.002 and 0.005, respectively). The associations between 1,25-OH2D3 and phosphate levels and AIx were observed for values within the normal range. No association was noted for calcium, iPTH, 25-OHD3, or hsCRP and AIx. Adjusting for potential confounders [eGFR, calcium, phosphate, and (log) iPTH] the association of lower 1,25-OH2D3 with AIx remained statistically significant.

Conclusion: This exploratory study demonstrates a significant association between AIx and 1,25-OH2D3 in a diverse group with cardiac, kidney disease, or both. These increasing understanding of the role of vitamin D in vascular health lends a context to these findings and raises questions as to additional modifiable risk factors in complex patients. Further studies are required.