Hemostasis biomarkers and incident cognitive impairment: the REGARDS study

• Published in: Journal of thrombosis and haemostasis Vol. 16; no. 7; pp. 1259 - 1267
• Main Authors: Gillett, S. R., McClure, L. A., Callas, P. W., Thacker, E. L., Unverzagt, F. W., Wadley, V. G., Letter, A. J., Cushman, M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Limited 01-07-2018
• Subjects: Biomarkers; Biomarkers - blood; Black or African American - psychology; Case-Control Studies; Coagulation factors; Cognition; Cognition Disorders - blood; Cognition Disorders - diagnosis; Cognition Disorders - ethnology; Cognitive ability; cognitive impairment; epidemiology; Factor VIII - analysis; Female; Fibrin Fibrinogen Degradation Products - analysis; Fibrinogen; Fibrinogen - analysis; Health Status Disparities; Hemostasis; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Prognosis; Prospective Studies; Protein C; Public health; Risk Assessment; risk factor; Risk Factors; thrombosis; Time Factors; United States - epidemiology; Up-Regulation; vascular cognitive impairment; Vascular diseases; White People - psychology; United States; vascular cognitive impairment; epidemiology; cognitive impairment; thrombosis; hemostasis; risk factor
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.14138

Essentials
Cognitive disorders are increasing and vascular risk factors play a role in this.
We performed a nested case control study of hemostasis biomarkers and cognitive impairment (CI).
Higher baseline fibrinogen, factor VIII and D‐dimer were related to incident CI over 3.5 years.
Adjusted for other risk factors, 2+ abnormal markers (but not single ones) led to higher risk.
Summary
Background
Vascular risk factors are associated with cognitive impairment, a condition that imposes a substantial public health burden. We hypothesized that hemostasis biomarkers related to vascular disease would be associated with the risk of incident cognitive impairment.
Methods
We performed a nested case–control study including 1082 participants with 3.5 years of follow‐up in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a longitudinal cohort study of 30 239 black and white Americans aged ≥ 45 years. Participants were free of stroke or cognitive impairment at baseline. Baseline D‐dimer, fibrinogen, factor VIII and protein C levels were measured in 495 cases who developed cognitive impairment during follow‐up (based on abnormal scores on two or more of three cognitive tests) and 587 controls.
Results
Unadjusted odds ratios (ORs) for incident cognitive impairment were 1.32 (95% confidence interval [CI] 1.02–1.70) for D‐dimer > 0.50 μg mL−1, 1.83 (95% CI 1.24–2.71) for fibrinogen > 90th percentile, 1.63 (95% CI 1.11–2.38) for FVIII > 90th percentile, and 1.10 (95% CI 0.73–1.65) for protein C < 10th percentile. There were no differences in associations by race or region. Adjustment for demographic, vascular and health behavior risk factors attenuated these associations. However, having at least two elevated biomarkers was associated with incident cognitive impairment, with an adjusted OR of 1.73 (95% CI 1.10–2.69).
Conclusion
Elevated D‐dimer, fibrinogen and FVIII levels were not associated with the occurrence of cognitive impairment after multivariable adjustment; however, having at least two abnormal biomarkers was associated with the occurrence of cognitive impairment, suggesting that the burden of these biomarkers is relevant.