Dataset Information

Cumulative Rheumatic Inflammation Modulates the Bone-Vascular Axis and Risk of Coronary Calcification.

ABSTRACT: Background Rheumatic diseases are related to both abnormal bone turnover and atherogenesis, but a mechanistic link was missing. Methods and Results We investigated the effect of cumulative rheumatic inflammation ( CRI ) on risk of coronary calcification in a retrospective cohort of 145 rheumatoid arthritis patients. A time-adjusted aggregate CRI score was derived by conglomerating all quarterly biomarker encounters of serum C-reactive protein over 60 months immediately preceding computed tomography coronary angiography. Flow cytometry was performed to measure the osteocalcin-positive ( OCN ⁺) CD 34⁺ KDR ⁺ and OCN ⁺ CD 34⁺ circulating endothelial progenitor cells ( EPCs ). Conventional early circulating EPCs CD 34⁺ CD 133⁺ KDR ⁺ was determined. Coronary calcification was defined as any Agatston score >0. 50% of patients (n=72/145) had coronary calcification. CRI score was associated with presence of coronary calcification ( P=0.004) (multivariable-adjusted: highest versus lowest quartile: odds ratio=5.6 [95% CI 1.1-28.9], P=0.041). Receiver operating characteristics curve revealed divergent behavior of OCN -expressing circulating EPCs ( OCN ⁺ CD 34⁺ EPCs : area under the curve=0.60, P=0.034; OCN ⁺ CD 34⁺ KDR ⁺ EPCs : area under the curve=0.59, P=0.053, positive predictors) versus conventional early EPCs ( CD 34⁺ CD 133⁺ KDR ⁺: area under the curve=0.60, P=0.034, negative predictor) for coronary calcification, which persisted after multivariable adjustments ( OCN ⁺ CD 34⁺ KDR ⁺ [>75th percentile]: odds ratio=7.2 [95% CI 1.8-27.9], P=0.005; OCN ⁺ CD 34⁺ EPCs [>75th percentile]: odds ratio=6.0 [95% CI 1.5-23.3], P=0.010; CD 34⁺ CD 133⁺ KDR ⁺ [>75th percentile: odds ratio=0.3 [95% CI 0.1-1.0], P=0.053). Intriguingly, the CRI score was associated with increased OCN ⁺ CD 34⁺ EPCs (highest versus lowest quartile: B=+25.6 [95% CI 0.8-50.5] [×10³/mL peripheral blood], P=0.043), but reduced CD 34⁺ CD 133⁺ KDR ⁺ EPCs (highest versus lowest quartile: B=-16.2 [95% CI -31.5 to -0.9], P=0.038). Conclusions Preceding 60 months of CRI is associated with increased risk of coronary calcification and altered OCN expression in circulating EPCs .

SUBMITTER: Chan YH

PROVIDER: S-EPMC6585350 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cumulative Rheumatic Inflammation Modulates the Bone-Vascular Axis and Risk of Coronary Calcification.

Chan Yap-Hang YH Ngai Michael Cheong MC Chen Yan Y Wu Mei-Zhen MZ Yu Yu-Juan YJ Zhen Zhe Z Lai Kevin K Cheung Tommy T Ho Lai-Ming LM Chung Ho-Yin HY Lau Chak-Sing CS Tse Hung-Fat HF Yiu Kai-Hang KH

Journal of the American Heart Association 20190601 11

Background Rheumatic diseases are related to both abnormal bone turnover and atherogenesis, but a mechanistic link was missing. Methods and Results We investigated the effect of cumulative rheumatic inflammation ( CRI ) on risk of coronary calcification in a retrospective cohort of 145 rheumatoid arthritis patients. A time-adjusted aggregate CRI score was derived by conglomerating all quarterly biomarker encounters of serum C-reactive protein over 60 months immediately preceding computed tomogra ...[more]

PMID: 31130038

Similar Datasets

Project description:An association between lower bone mineral density (BMD) and presence of vascular calcification (VC) has been reported in several studies. Chronic kidney disease (CKD) causes detrimental disturbances in the mineral balance, bone turnover, and development of severe VC. Our group has previously demonstrated expression of Wnt inhibitors in calcified arteries of CKD rats. Therefore, we hypothesized that the CKD-induced VC via this pathway signals to bone and induces bone loss. To address this novel hypothesis, we developed a new animal model using isogenic aorta transplantation (ATx). Severely calcified aortas from uremic rats were transplanted into healthy rats (uremic ATx). Transplantation of normal aortas into healthy rats (normal ATx) and age-matched rats (control) served as control groups. Trabecular tissue mineral density, as measured by μCT, was significantly lower in uremic ATx rats compared with both control groups. Uremic ATx rats showed a significant upregulation of the mineralization inhibitors osteopontin and progressive ankylosis protein homolog in bone. In addition, we found significant changes in bone mRNA levels of several genes related to extracellular matrix, bone turnover, and Wnt signaling in uremic ATx rats, with no difference between normal ATx and control. The bone histomorphometry analysis showed significant lower osteoid area in uremic ATx compared with normal ATx along with a trend toward fewer osteoblasts as well as more osteoclasts in the erosion lacunae. Uremic ATx and normal ATx had similar trabecular number and thickness. The bone formation rate did not differ between the three groups. Plasma biochemistry, including sclerostin, kidney, and mineral parameters, were similar between all three groups. ex vivo cultures of aorta from uremic rats showed high secretion of the Wnt inhibitor sclerostin. In conclusion, the presence of VC lowers BMD, impairs bone metabolism, and affects several pathways in bone. The present results prove the existence of a vasculature to bone tissue cross-talk. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Dataset Information

Cumulative Rheumatic Inflammation Modulates the Bone-Vascular Axis and Risk of Coronary Calcification.

Publications

Cumulative Rheumatic Inflammation Modulates the Bone-Vascular Axis and Risk of Coronary Calcification.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets