Thromb Haemost 2019; 119(05): 834-843
DOI: 10.1055/s-0039-1678737
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Plasma Concentrations of High Molecular Weight Kininogen and Prekallikrein and Venous Thromboembolism Incidence in the General Population

Aaron R. Folsom
1  Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States
,
Weihong Tang
1  Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States
,
Saonli Basu
2  Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States
,
1  Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States
,
David Couper
3  Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
,
Susan R. Heckbert
4  Department of Epidemiology, University of Washington, Seattle, Washington, United States
,
Mary Cushman
5  Department of Medicine, University of Vermont, Burlington, Vermont, United States
6  Department of Pathology, University of Vermont, Burlington, Vermont, United States
› Author Affiliations
Funding The National Heart, Lung, and Blood Institute provided support for venous thromboembolism identification via R01 HL059367 and for the Atherosclerosis Risk in Communities Study via contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I and HHSN268201700005I.
Further Information

Publication History

22 August 2018

04 January 2019

Publication Date:
19 February 2019 (eFirst)

Abstract

The kallikrein/kinin system, an intravascular biochemical pathway that includes several proteins involved in the contact activation system of coagulation, renin–angiotensin activation and inflammation, may or may not play a role in venous thromboembolism (VTE) occurrence. Within a large prospective population-based study in the United States, we conducted a nested case–cohort study to test the hypothesis that higher plasma levels of high molecular weight kininogen (HK) or prekallikrein are associated with greater VTE incidence. We related baseline enzyme-linked immunosorbent assay measures of HK and prekallikrein in 1993 to 1995 to incidence VTE of the lower extremity (n = 612) through 2015 (mean follow-up = 18 years). We found no evidence that plasma HK or prekallikrein was associated positively with incident VTE. HK, in fact, was associated inversely and significantly with VTE in most proportional hazards regression models. For example, the hazard ratio of VTE per standard deviation higher HK concentration was 0.88 (95% confidence interval = 0.81, 0.97), after adjustment for several VTE risk factors. Our findings suggest that plasma levels of these factors do not determine the risk of VTE in the general population.

Authors' Contributions

Aaron R. Folsom had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The contributions of the authors are as follows:


A. R. Folsom: Study conception and design, analysed the data, acquisition of data, drafted the manuscript and final approval of the manuscript.


W. Tang: Provided critical revisions to the manuscript, and final approval of the manuscript.


S. Basu: Study conception and design, provided critical revisions to the manuscript and final approval of the manuscript.


J. R. Misialek: Analysed the data, provided critical revisions to the manuscript and final approval of the manuscript.


D. Couper: Analysed the data, provided critical revisions to the manuscript and final approval of the manuscript.


S. R. Heckbert: Provided critical revisions to the manuscript, and final approval of the manuscript.


M. Cushman: Study conception and design, acquisition of data, provided critical revisions to the manuscript and final approval of the manuscript.