Inflammation and Thrombosis Biomarkers and Incident Frailty in Postmenopausal Women
published online 14 August 2009.
Abstract
Background
The immune and blood coagulation systems have been implicated in the pathophysiology of the geriatric syndrome of frailty, but limited prospective data examining the relationship of clotting/inflammation biomarkers to risk of incident frailty exist.
Methods
This prospective analysis was derived from a nested case-control study within the Women's Health Initiative. Among women 65 to 79 years free of frailty at enrollment, we randomly selected 900 incident cases from those developing frailty within 3 years; 900 non-frail controls were individually matched on age, ethnicity, and blood collection date. Biomarkers assessed for risk of incident frailty included fibrinogen, factor VIII, D-dimer, C-reactive protein, interleukin-6, and tissue plasminogen activator (t-PA).
Results
When examined by quartiles in multivariable adjusted models, higher D-dimer and t-PA levels were each associated with increased risk of frailty (P trend = .04). Relative to the lowest quartile, the odds ratios for frailty compared with the upper quartile were 1.52 (95% confidence interval, 1.05-2.22) for t-PA and 1.57 (95% confidence interval, 1.11-2.22) for D-dimer. For women having high t-PA and high D-dimer compared with women having lower levels of both biomarkers, the odds of frailty was 2.20 (1.29-3.75). There was little evidence for association between coagulation factor VIII, fibrinogen, C-reactive protein, or interleukin-6 levels and incident frailty.
Conclusion
This prospective analysis supports the role of markers of fibrin turnover and fibrinolysis as independent predictors of incident frailty in postmenopausal women.
aWomen's Health Initiative Clinical Coordinating Center, Fred Hutchinson Cancer Research Center, Seattle, Wash
bDepartment of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Wash
cDepartment of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, Wash
dGeriatric Pharmacy Program, School of Pharmacy, University of Washington, Seattle, Wash
eSchool of Nursing, University of Washington, Seattle, Wash
fDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, Penn
gDepartment of Social and Preventive Medicine, University at Buffalo, Buffalo, NY
Reprint requests should be addressed to Alexander P. Reiner, MD, Department of Epidemiology, Box 357236, University of Washington, Seattle, WA 98195
Funding: The Women's Health Initiative program is funded by the National Heart, Lung, and Blood Institute, US Department of Health and Human Services. A full listing of Women's Health Initiative investigators can be found at http://www.whiscience.org/publications/WHI_investigators_shortlist.pdf. This article was supported by grant R01 AG025441 to Dr LaCroix from the National Institute of Aging.
Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript.
Authorship: All authors had access to the data and played a role in writing this manuscript.
ABSTRACT
