Hemostasis biomarkers and incident cognitive impairment: the REGARDS study

S. R. Gillett, L. A. McClure, P. W. Callas, E. L. Thacker, Frederick Unverzagt, V. G. Wadley, A. J. Letter, M. Cushman

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1259-1267
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume16
Issue number7
DOIs
StatePublished - Jul 1 2018

Fingerprint

Hemostasis
Biomarkers
Stroke
Fibrinogen
Factor VIII
Protein C
Cognitive Dysfunction
Odds Ratio
Social Adjustment
Health Behavior
Vascular Diseases
Blood Vessels
Longitudinal Studies
Case-Control Studies
Cohort Studies
Public Health
Demography

Keywords

  • cognitive impairment
  • epidemiology
  • hemostasis
  • risk factor
  • thrombosis
  • vascular cognitive impairment

ASJC Scopus subject areas

  • Hematology

Cite this

Gillett, S. R., McClure, L. A., Callas, P. W., Thacker, E. L., Unverzagt, F., Wadley, V. G., ... Cushman, M. (2018). Hemostasis biomarkers and incident cognitive impairment: the REGARDS study. Journal of Thrombosis and Haemostasis, 16(7), 1259-1267. https://doi.org/10.1111/jth.14138

Hemostasis biomarkers and incident cognitive impairment : the REGARDS study. / Gillett, S. R.; McClure, L. A.; Callas, P. W.; Thacker, E. L.; Unverzagt, Frederick; Wadley, V. G.; Letter, A. J.; Cushman, M.

In: Journal of Thrombosis and Haemostasis, Vol. 16, No. 7, 01.07.2018, p. 1259-1267.

Research output: Contribution to journalArticle

Gillett, SR, McClure, LA, Callas, PW, Thacker, EL, Unverzagt, F, Wadley, VG, Letter, AJ & Cushman, M 2018, 'Hemostasis biomarkers and incident cognitive impairment: the REGARDS study', Journal of Thrombosis and Haemostasis, vol. 16, no. 7, pp. 1259-1267. https://doi.org/10.1111/jth.14138
Gillett, S. R. ; McClure, L. A. ; Callas, P. W. ; Thacker, E. L. ; Unverzagt, Frederick ; Wadley, V. G. ; Letter, A. J. ; Cushman, M. / Hemostasis biomarkers and incident cognitive impairment : the REGARDS study. In: Journal of Thrombosis and Haemostasis. 2018 ; Vol. 16, No. 7. pp. 1259-1267.
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abstract = "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.",
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N2 - 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.

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