Inflammation and thrombosis biomarkers and incident frailty in postmenopausal women.
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.


CONCLUSIONS
This prospective analysis supports the role of markers of fibrin turnover and fibrinolysis as independent predictors of incident frailty in postmenopausal women.
Reiner
Alexander P
AP
Women's Health Initiative Clinical Coordinating Center, Fred Hutchinson Cancer Research Center, Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA. apreiner@u.washington.edu
Aragaki
Aaron K
AK
Gray
Shelly L
SL
Wactawski-Wende
Jean
J
Cauley
Jane A
JA
Cochrane
Barbara B
BB
Kooperberg
Charles L
CL
Woods
Nancy F
NF
LaCroix
Andrea Z
AZ
D000368:Aged; D000375:Aging / Q000097:blood / Q000502:physiology; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D016001:Confidence Intervals; D005169:Factor VIII / Q000032:analysis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005500:Follow-Up Studies; D016330:Frail Elderly; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D015999:Multivariate Analysis; D017698:Postmenopause / Q000097:blood* / Q000502:physiology; D011336:Probability; D011446:Prospective Studies; D018570:Risk Assessment; D013927:Thrombosis / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D010959:Tissue Plasminogen Activator / Q000097:blood; D016387:Women's Health
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D005169:Factor VIII; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator
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