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Total tissue factor pathway inhibitor and venous thrombosis. The Longitudinal Investigation of Thromboembolism Etiology.

TitleTotal tissue factor pathway inhibitor and venous thrombosis. The Longitudinal Investigation of Thromboembolism Etiology.
Publication TypeJournal Article
Year of Publication2010
AuthorsZakai NA, Lutsey PL, Folsom AR, Heckbert SR, Cushman M
JournalThromb Haemost
Volume104
Issue2
Pagination207-12
Date Published2010 Aug
ISSN2567-689X
KeywordsBiomarkers, Blood Coagulation, Case-Control Studies, Chi-Square Distribution, Down-Regulation, Female, Humans, Lipoproteins, Logistic Models, Longitudinal Studies, Male, Middle Aged, Odds Ratio, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States, Venous Thromboembolism, Venous Thrombosis
Abstract

Tissue factor pathway inhibitor (TFPI) inhibits tissue factor, a potent coagulation initiator. Limited evidence suggests that low TFPI levels are associated with increased risk of venous thromboembolism (VTE). We measured total TFPI in a nested case-control study in the Longitudinal Investigation of Thromboembolism Etiology. Control subjects were frequency matched 2:1 to cases on age, sex, race, and cohort. Odds ratios (ORs) for VTE by TFPI levels were computed using logistic regression models adjusting for age, race, sex, coagulation factors (factors VII, VIII, IX, XI, D-dimer), and body mass index (BMI). To evaluate for greater than additive interactions, we calculated the percent relative excess risk due to interaction between TFPI and other VTE risk factors. A total of 534 cases of VTE occurred and matched to 1,091 controls. Mean baseline TFPI in ng/ml (standard deviation) in those who developed VTE and controls was 36.4 (12.8) and 35.0 (11.1), respectively. Higher TFPI was associated with male sex, age, BMI, factors VII, VIII, IX, XI, and D-dimer. TFPI level did not differ by ethnicity, factor V Leiden, or prothrombin G20210A. Compared with those in the upper 95%, the bottom 5% of TFPI had an age-, sex-, race-, and study-adjusted OR (95% CI) of 1.35 (0.86, 2.12) for VTE. Adjusting for factors VII, VIII, IX, and XI the OR was 1.93 (1.05, 3.53). Further addition of D-dimer and BMI to this model decreased the OR to 1.70 (0.98, 2.93). Low TFPI did not demonstrate greater than additive interaction with other VTE risk factors.

DOI10.1160/TH09-10-0693
Alternate JournalThromb Haemost
PubMed ID20431849
PubMed Central IDPMC2943145
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
N01 HC055022 / HC / NHLBI NIH HHS / United States
N01 HC085086 / HC / NHLBI NIH HHS / United States
R01 HL059367-02 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
N01 HC085081 / HC / NHLBI NIH HHS / United States
R01HL054711 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01 HC085083 / HC / NHLBI NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
R01 HL59367 / HL / NHLBI NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01-HC55019 / HC / NHLBI NIH HHS / United States
N01 HC085082 / HC / NHLBI NIH HHS / United States
R01-HL-59367 / HL / NHLBI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
N01 HC085080 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01 HC055015 / HC / NHLBI NIH HHS / United States
N01 HC055021 / HC / NHLBI NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
N01 HC055020 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 HL054711-03 / HL / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
N01 HC055016 / HC / NHLBI NIH HHS / United States