Inflammation markers and incident venous thromboembolism: the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort

• Published in: Journal of thrombosis and haemostasis Vol. 12; no. 12; pp. 1993 - 2001
• Main Authors: Olson, N. C., Cushman, M., Lutsey, P. L., McClure, L. A., Judd, S., Tracy, R. P., Folsom, A. R., Zakai, N. A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Limited 01-12-2014
• Subjects: Aged; biomarkers; Biomarkers - metabolism; Body Mass Index; C-Reactive Protein - metabolism; Cohort Studies; C‐reactive protein; Female; Humans; inflammation; Inflammation - blood; Longitudinal Studies; Male; Middle Aged; Obesity - blood; Proportional Hazards Models; Prospective Studies; Risk Factors; serum albumin; Serum Albumin - metabolism; Stroke - blood; Stroke - ethnology; Stroke - physiopathology; venous thromboembolism; Venous Thromboembolism - blood; Venous Thromboembolism - ethnology; Venous Thromboembolism - physiopathology; C-reactive protein; serum albumin; inflammation; biomarkers; venous thromboembolism
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.12742

Summary
Background
Inflammation biomarkers are associated with the venous thromboembolism (VTE) risk factors obesity and age; however, the relationships of inflammation with VTE risk remain controversial.
Objectives
To examine associations of four inflammation biomarkers, i.e. C‐reactive protein (CRP), serum albumin, white blood cell (WBC) count, and platelet count (PLTC), with incident VTE, and to determine whether they mediate the association of age or obesity with VTE.
Patients/Methods
Hazards models adjusted for VTE risk factors were used to calculate the prospective association of each biomarker with incident VTE in 30 239 participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Mediation of the associations of obesity and age with VTE were examined by bootstrapping. Over a period of 4.6 years, there were 268 incident VTE events. After adjustment for VTE risk factors, the hazard ratios (HRs) were 1.25 (95% confidence interval [CI] 1.09–1.43) per standard deviation (SD) higher log‐CRP and 1.25 (95% CI 1.06–1.48) per SD lower albumin; there were no associations for WBC count or PLTC. The association of body mass index (BMI), but not age, with VTE was partially mediated by CRP and albumin. In risk factor‐adjusted models, the percentage attenuations of the BMI HR for VTE after introduction of CRP or albumin into the models were 15.4% (95% CI 7.7–33.3%) and 41.0% (95% CI 12.8–79.5%), respectively.
Conclusion
Higher CRP levels and lower serum albumin levels were associated with increased VTE risk, and statistically mediated part of the association of BMI with VTE. These data suggest that inflammation may be a potential mechanism underlying the relationship between obesity and VTE risk.