TY - JOUR
T1 - Circulating Adipokines and Associations With Incident Cardiovascular Disease in Rheumatoid Arthritis
AU - Federico, Lydia E.
AU - Johnson, Tate M.
AU - England, Bryant R.
AU - Wysham, Katherine D.
AU - George, Michael D.
AU - Sauer, Brian
AU - Hamilton, Bartlett C.
AU - Hunter, Carlos D.
AU - Duryee, Michael J.
AU - Thiele, Geoffrey M.
AU - Mikuls, Ted R.
AU - Baker, Joshua F.
N1 - Funding Information:
Supported by the Center of Excellence for Suicide Prevention, Joint Department of Veterans Affairs and Department of Defense Mortality Data Repository, National Death Index. Dr. England's work was supported by the Veterans Affairs Career Development Award (grant IK2CX002203). Dr. Wysham's work was supported by the Department of Veterans Affairs and the Rheumatology Research Foundation. Dr. George's work was supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K23‐AR‐073931). Dr. Mikuls' work was supported by the Department of Veterans Affairs (Merit Award grant I01BX0046000), the Department of Defense (grant PR200793), and the NIH (National Institute on Alcohol Abuse and Alcoholism grant R25‐AA‐020818, National Institute of General Medical Sciences grant U54‐GM‐115458, and National Institute of Arthritis and Musculoskeletal and Skin Diseases grant P50‐AR‐60772). Dr. Baker's work was supported by the Department of Veterans Affairs (Clinical Science Research and Development Career Merit Award grant I01CX001703 and Rehabilitation Research and Development grants I21CX003157 and I01CX003644).
Publisher Copyright:
© 2022 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
PY - 2022
Y1 - 2022
N2 - Objective: To assess whether circulating levels of adiponectin, leptin, and fibroblast growth factor 21 (FGF-21) are associated with incident cardiovascular disease (CVD) in rheumatoid arthritis (RA). Methods: Adipokines were measured using banked enrollment serum from patients with RA and dichotomized above/below the median value. Incident CVD events (coronary artery disease [CAD], stroke, heart failure [HF] hospitalization, venous thromboembolism, CVD-related deaths) were identified using administrative data and the National Death Index. Covariates were derived from medical record, biorepository, and registry databases. Multivariable Cox models were generated to quantify associations between adipokine concentrations and CVD incidence. Five-year incidence rates were predicted. Results: Among 2,598 participants, 639 (25%) had at least 1 CVD event over 19,585 patient-years of follow-up. High adiponectin levels were independently associated with HF hospitalization (hazard ratio [HR] 1.39 [95% confidence interval (95% CI) 1.07–1.79], P = 0.01) and CVD-related death (HR 1.49 [95% CI 1.16–1.92], P = 0.002) but not with other CVD events. High leptin was independently associated with CVD-related death (HR 1.44 [95% CI 1.05–1.97], P = 0.02). High FGF-21 levels were independently associated with lower rates of CAD (HR 0.75 [95% CI 0.58–0.97], P = 0.03). In subgroup analyses, associations between high adiponectin and leptin levels with CVD-related death were driven by strong associations in nonobese patients. Conclusion: Adipokines are associated with HF hospitalization and CVD-related death in patients with RA, with stronger associations in nonobese participants. These findings suggest that adipokines effectively predict clinically important outcomes in RA perhaps through an association with body composition and metabolic health. Further study is needed to determine whether adipokine measures might augment existing tools to identify RA patients at increased risk of CVD.
AB - Objective: To assess whether circulating levels of adiponectin, leptin, and fibroblast growth factor 21 (FGF-21) are associated with incident cardiovascular disease (CVD) in rheumatoid arthritis (RA). Methods: Adipokines were measured using banked enrollment serum from patients with RA and dichotomized above/below the median value. Incident CVD events (coronary artery disease [CAD], stroke, heart failure [HF] hospitalization, venous thromboembolism, CVD-related deaths) were identified using administrative data and the National Death Index. Covariates were derived from medical record, biorepository, and registry databases. Multivariable Cox models were generated to quantify associations between adipokine concentrations and CVD incidence. Five-year incidence rates were predicted. Results: Among 2,598 participants, 639 (25%) had at least 1 CVD event over 19,585 patient-years of follow-up. High adiponectin levels were independently associated with HF hospitalization (hazard ratio [HR] 1.39 [95% confidence interval (95% CI) 1.07–1.79], P = 0.01) and CVD-related death (HR 1.49 [95% CI 1.16–1.92], P = 0.002) but not with other CVD events. High leptin was independently associated with CVD-related death (HR 1.44 [95% CI 1.05–1.97], P = 0.02). High FGF-21 levels were independently associated with lower rates of CAD (HR 0.75 [95% CI 0.58–0.97], P = 0.03). In subgroup analyses, associations between high adiponectin and leptin levels with CVD-related death were driven by strong associations in nonobese patients. Conclusion: Adipokines are associated with HF hospitalization and CVD-related death in patients with RA, with stronger associations in nonobese participants. These findings suggest that adipokines effectively predict clinically important outcomes in RA perhaps through an association with body composition and metabolic health. Further study is needed to determine whether adipokine measures might augment existing tools to identify RA patients at increased risk of CVD.
UR - http://www.scopus.com/inward/record.url?scp=85142315614&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85142315614&partnerID=8YFLogxK
U2 - 10.1002/acr.24885
DO - 10.1002/acr.24885
M3 - Article
C2 - 35313088
AN - SCOPUS:85142315614
SN - 2151-4658
JO - Arthritis care & research
JF - Arthritis care & research
ER -