Thrombo-inflammatory biomarkers and D-dimer in a biracial cohort study

Debora Kamin Mukaz, Mansour Gergi, Insu Koh, Neil A Zakai, Suzanne E Judd, Michelle Sholzberg, Lisa Baumann Kreuziger, Kalev Freeman, Christos Colovos, Nels C Olson, Mary Cushman, Debora Kamin Mukaz, Mansour Gergi, Insu Koh, Neil A Zakai, Suzanne E Judd, Michelle Sholzberg, Lisa Baumann Kreuziger, Kalev Freeman, Christos Colovos, Nels C Olson, Mary Cushman

Abstract

Background: Higher D-dimer is a risk factor for cardiovascular diseases and venous thromboembolism. In the general population, D-dimer and other thrombo-inflammatory biomarkers are higher among Black individuals, who also have higher risk of these conditions compared to White people.

Objective: To assess whether Black individuals have an exaggerated correlation between D-dimer and thrombo-inflammatory biomarkers characteristic of cardiovascular diseases.

Methods: Linear regression was used to assess correlations of 11 thrombo-inflammatory biomarkers with D-dimer in a cross-sectional study of 1068 participants of the biracial Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.

Results: Adverse levels of most biomarkers, especially fibrinogen, factor VIII, C-reactive protein, N-terminal pro-B-type natriuretic peptide, and interleukin (IL)-6, were associated with higher D-dimer. Several associations with D-dimer differed significantly by race. For example, the association of factor VIII with D-dimer was more than twice as large in Black compared to White participants. Specifically, D-dimer was 26% higher per standard deviation (SD) higher factor VIII in Black adults and was only 11% higher per SD higher factor VIII in White adults. In Black but not White adults, higher IL-10 and soluble CD14 were associated with higher D-dimer.

Conclusions: Findings suggest that D-dimer might relate to Black/White differences in cardiovascular diseases and venous thromboembolism because it is a marker of amplified thrombo-inflammatory response in Black people. Better understanding of contributors to higher D-dimer in the general population is needed.

Keywords: D‐dimer; biomarkers; cardiovascular diseases; race; thrombo‐inflammation.

© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).

Figures

FIGURE 1
FIGURE 1
Difference in associations of biomarkers with D‐dimer. The difference in association of each biomarker with D‐dimer is shown by race, including biomarkers with interaction P value <.05 for race difference. Values shown are percent difference in D‐dimer per SD increment of each biomarker, thus results may be compared across biomarkers as to their magnitude. Error bars indicate 95% confidence intervals. Models are adjusted for age and sex. IL, interleukin; sCD14, soluble CD14
FIGURE 2
FIGURE 2
Partial regression plots showing the association of thrombo‐inflammatory biomarkers with log D‐dimer, after adjustment for age and sex, in Black and White participants. FVIII, factor VIII; IL, interleukin; sCD14, soluble CD14

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