E Blair Solow1, Fang Yu2, Geoffrey M Thiele3, Jeremy Sokolove4, William H Robinson4, Zachary M Pruhs3, Kaleb D Michaud5, Alan R Erickson3, Harlan Sayles3, Gail S Kerr6, Angelo L Gaffo7, Liron Caplan8, Lisa A Davis8, Grant W Cannon9, Andreas M Reimold10, Joshua Baker11, Pascale Schwab12, Daniel R Anderson13, Ted R Mikuls14. 1. Division of Rheumatic Diseases, UT Southwestern, Dallas, TX. 2. Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha. 3. Division of Rheumatology and Immunology, Omaha Veterans Affairs Medical Center, Omaha, NE. 4. Division of Rheumatology, VA Palo Alto Health Care System, Palo Alto, CA. 5. Division of Rheumatology and Immunology, Omaha Veterans Affairs Medical Center, Omaha, NE, National Data Bank for Rheumatic Diseases, Wichita, KS. 6. Department of Medicine, Veterans Affairs Medical Center, Washington, DC. 7. Department of Medicine, Birmingham Veterans Affairs Medical Center, Birmingham, AL. 8. Division of Rheumatology, Denver Veterans Affairs Medical Center, Denver, CO. 9. Division of Rheumatology, George Wahlen Veterans Affairs Medical Center, Salt Lake City, UT. 10. Division of Rheumatic Diseases, UT Southwestern, Dallas, TX, Division of Rheumatology, Dallas Veterans Affairs Medical Center, Dallas, TX. 11. Division of Rheumatology, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA. 12. Division of Rheumatology, Portland Veterans Affairs Medical Center, Portland, OR and. 13. Division of Cardiology, University of Nebraska Medical Center, Omaha, NE. 14. Division of Rheumatology and Immunology, Omaha Veterans Affairs Medical Center, Omaha, NE, tmikuls@unmc.edu.
Abstract
OBJECTIVE: To examine whether vascular calcifications on hand films in RA might aid in determining mortality risk. METHODS: Hand radiographs from 906 RA patients were scored as positive or negative for vascular calcifications. Patient characteristics associated with vascular calcifications were assessed using multivariable logistic regression, and associations with mortality were examined using Cox proportional hazards regression. Cytokines and multiplex ACPA were measured in both groups. RESULTS: A total of 99 patients (11%) demonstrated radiographic vascular calcifications. Factors independently associated with vascular calcifications included diabetes [odds ratio (OR) 2.85; 95% CI 1.43, 5.66], cardiovascular disease at enrolment (OR 2.48; 95% CI 1.01, 6.09), prednisone use (OR 1.90; 95% CI 1.25, 2.91), current smoking (OR 0.06; 95% CI 0.01, 0.23) and former smoking (OR 0.36; 95% CI 0.27, 0.48) vs never smoking. In cytokine and ACPA subtype analysis, IL-4 and anti-citrullinated apolipoprotein E were significantly increased in patients with vascular calcifications in fully adjusted multivariable models. After multivariable adjustment, vascular calcifications were associated with an increase in all-cause mortality (hazard ratio 1.41; 95% CI 1.12, 1.78; P = 0.004). CONCLUSION: Vascular calcifications on hand radiographs were independently associated with increased all-cause mortality in RA. Mechanisms underpinning the associations of IL-4 and select ACPA with vascular calcifications and their utility as biomarkers predictive of cardiovascular disease risk in RA merit further study. Published by Oxford University Press on behalf of the British Society for Rheumatology 2015. This work is written by US Government employees and is in the public domain in the US.
OBJECTIVE: To examine whether vascular calcifications on hand films in RA might aid in determining mortality risk. METHODS: Hand radiographs from 906 RApatients were scored as positive or negative for vascular calcifications. Patient characteristics associated with vascular calcifications were assessed using multivariable logistic regression, and associations with mortality were examined using Cox proportional hazards regression. Cytokines and multiplex ACPA were measured in both groups. RESULTS: A total of 99 patients (11%) demonstrated radiographic vascular calcifications. Factors independently associated with vascular calcifications included diabetes [odds ratio (OR) 2.85; 95% CI 1.43, 5.66], cardiovascular disease at enrolment (OR 2.48; 95% CI 1.01, 6.09), prednisone use (OR 1.90; 95% CI 1.25, 2.91), current smoking (OR 0.06; 95% CI 0.01, 0.23) and former smoking (OR 0.36; 95% CI 0.27, 0.48) vs never smoking. In cytokine and ACPA subtype analysis, IL-4 and anti-citrullinated apolipoprotein E were significantly increased in patients with vascular calcifications in fully adjusted multivariable models. After multivariable adjustment, vascular calcifications were associated with an increase in all-cause mortality (hazard ratio 1.41; 95% CI 1.12, 1.78; P = 0.004). CONCLUSION:Vascular calcifications on hand radiographs were independently associated with increased all-cause mortality in RA. Mechanisms underpinning the associations of IL-4 and select ACPA with vascular calcifications and their utility as biomarkers predictive of cardiovascular disease risk in RA merit further study. Published by Oxford University Press on behalf of the British Society for Rheumatology 2015. This work is written by US Government employees and is in the public domain in the US.
Entities:
Keywords:
anti-citrullinated protein autoantibodies; hand radiographs; mortality; rheumatoid arthritis; vascular calcifications
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