Plasma homocysteine and the risk of venous thromboembolism: insights from the FIELD study

Markus Herrmann, Malcolm Whiting, Anne-Sophie Veillard, Christian Ehnholm, David Sullivan, Anthony Keech

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    22 Citations (Scopus)

    Abstract

    Background: The lipid-lowering effect of fenofibrate is accompanied by a rise in plasma homocysteine (HCY), a potential risk factor for venous thromboembolism (VTE). This study investigated the relationship between HCY and the risk of VTE in patients treated with fenofibrate. Methods: The relationship between HCY and deep-vein thrombosis or pulmonary embolism was investigated in 9522 participants of the 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. All subjects received fenofibrate during a 6-week active run-in phase before randomization. A Cox proportional-hazards model was used to assess the effect of HCY on risk of venous thromboembolic events. Results: During active-drug run-in, HCY rose on average by 6.5 μmol/L, accompanied by a substantial rise in plasma creatinine (+ 12%). Fenofibrate-induced changes in HCY and creatinine were fully reversible in the placebo group but persisted in the treatment group until reversing at the end of therapy. During follow-up, 1.8% had at least one episode of deep-vein thrombosis or pulmonary embolism: 103 on fenofibrate and 68 on placebo (log-rank p=0.006). In multivariate analysis, every 5 μmol/L higher baseline HCY was associated with 19% higher risk of VTE. Fenofibrate treatment was associated with 52% higher risk, but the change in HCY with fenofibrate was not significantly associated with VTE after adjustment for baseline HCY. Conclusions: Hyperhomocysteinemia is prospectively associated with VTE. Fenofibrate may predispose individuals with high pretreatment HCY towards VTE. The fenofibrateinduced increase in HCY did not, however, explain the risk associated with fenofibrate therapy.

    Original languageEnglish
    Pages (from-to)2213-2219
    Number of pages7
    JournalClinical Chemistry and Laboratory Medicine
    Volume50
    Issue number12
    DOIs
    Publication statusPublished - Dec 2012

    Keywords

    • Diabetes mellitus
    • Fenofibrate
    • Homocysteine
    • Pulmonary embolism
    • Thrombosis

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