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

TitlePlasma Concentrations of High Molecular Weight Kininogen and Prekallikrein and Venous Thromboembolism Incidence in the General Population.
Publication TypeJournal Article
Year of Publication2019
AuthorsFolsom AR, Tang W, Basu S, Misialek JR, Couper DJ, Heckbert SR
Secondary AuthorsCushman M
JournalThromb Haemost
Volume119
Issue5
Pagination834-843
Date Published2019 May
ISSN2567-689X
KeywordsBlood Coagulation, Case-Control Studies, Cohort Studies, Female, Follow-Up Studies, Humans, Incidence, Kallikrein-Kinin System, Kininogen, High-Molecular-Weight, Male, Middle Aged, Plasma, Population Groups, Prekallikrein, Prospective Studies, Risk, United States, Venous Thromboembolism
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 ( = 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.

DOI10.1055/s-0039-1678737
Alternate JournalThromb Haemost
PubMed ID30780167
PubMed Central IDPMC6499653
Grant ListR01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201700002C / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
HHSN268201700005C / HL / NHLBI NIH HHS / United States
HHSN268201700001C / HL / NHLBI NIH HHS / United States
HHSN268201700003C / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States