Plasma homocysteine and the risk of venous thromboembolism: insights from the FIELD study
- 15 July 2012
- journal article
- research article
- Published by Walter de Gruyter GmbH in cclm
- Vol. 50 (12), 2213-2219
- https://doi.org/10.1515/cclm-2012-0078
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 fenofibrate-induced increase in HCY did not, however, explain the risk associated with fenofibrate therapy.Keywords
This publication has 38 references indexed in Scilit:
- A genome-wide association study of inflammatory biomarker changes in response to fenofibrate treatment in the Genetics of Lipid Lowering Drug and Diet NetworkPharmacogenetics and Genomics, 2012
- The effect of fenofibrate on lymphocyte cytokine release in patients with impaired fasting glucose and impaired glucose tolerance: A preliminary reportAtherosclerosis, 2010
- Homocysteine-mediated thrombosis and angiostasis in vascular pathobiologyJCI Insight, 2009
- How Can We Improve the Management of Vascular Risk in Type 2 Diabetes: Insights from FIELDCardiovascular Drugs and Therapy, 2009
- Mild hyperhomocysteinemia is associated with increased TAFI levels and reduced plasma fibrinolytic potentialJournal of Thrombosis and Haemostasis, 2008
- Fenofibrate activates the biochemical pathways and the de novo expression of genes related to lipid handling and uncoupling protein-3 functions in liver of normal ratsBiochimica et Biophysica Acta (BBA) - Bioenergetics, 2006
- Common C677T Polymorphism of the Methylenetetrahydrofolate Reductase Gene and the Risk of Venous Thromboembolism: Meta-Analysis of 31 StudiesPathophysiology of Haemostasis and Thrombosis, 2002
- Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)JAMA, 2001
- Interaction between Hyperhomocysteinemia and Inherited Thrombophilic Factors in Venous ThromboembolismSeminars in Thrombosis and Hemostasis, 2000
- Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitusKidney International, 1999