Abstract
Background
Rheumatoid arthritis is associated with both abnormal bone metabolism and atherogenesis but mechanistic links were missing.
Aim
This study aimed to investigate the role of osteocalcin (OCN)-expressing circulating endothelial progenitor cells (EPC)s in the severity and dissemination of systemic arterial calcifications in rheumatoid arthritis.
Methods
We performed flow cytometry studies in 145 consecutive patients with rheumatoid arthritis to determine osteogenic circulating levels of OCN-positive (OCN+) CD34+KDR+ and OCN+CD34+, versus conventional early EPC CD34+CD133+KDR+. Total calcium load of the thoracic aorta (ascending plus descending) and the carotid arteries were assessed by non-contrast computed tomography (CT) and contrast CT angiography.
Results
Osteogenic EPCs OCN+CD34+KDR+ (P=0.002) and OCN+CD34+ were strikingly associated with the clustered presence of aortic and carotid calcification (P=0.002 and 0.001 respectively, Figure). Multivariable analyses revealed that circulating OCN+CD34+KDR+ (B=14.4 [95% CI 4.0 to 24.8], P=0.007) and OCN+CD34+ (B=9.6 [95% CI 4.9 to 14.3], P<0.001) remained independently associated with increased aortic calcium load. OCN+CD34+ EPC (B=0.8 [95% CI 0.1 to 1.5], P=0.023), but not OCN+CD34+KDR+ EPC (B=1.2 [95% CI −0.2 to 2.6], P=0.09) was further independently associated with carotid calcium load. In comparison, conventional early EPC CD34+CD133+KDR+ had no significant association with aortic or carotid calcium load (P=0.46 and 0.88, respectively).
Conclusions
Circulating level of osteogenic EPC is associated with promulgated aortic and carotid calcification in patients with rheumatoid arthritis, suggesting a potential mechanistic role of the bone-vascular axis in pro-atherogenicity of rheumatic diseases.
Acknowledgement/Funding
General Research Fund, Hong Kong Research Grants Council