The prevention of recurrent venous thrombosis (VT) is paramount among the clinical challenges currently facing practitioners treating VT. Identifying patients at risk is made difficult by the fact that risk factors for VT recurrence are poorly characterized. Only recently has there been insight into the acquired and inherited characteristics that influence subsequent risk of a new thrombotic event in adults with a confirmed first event. As a result, there is little evidence to inform and guide treatment and prophylaxis decisions. In addition, treatment options to prevent recurrent VT are limited. Pharmaceutical anti-coagulation interventions are most effective but advantages need to be weighed against the risk of life-threatening bleeding. Using a population- based inception cohort of 2,100 incident VT patients with longitudinal data on clinical characteristics and pharmaceutical treatments, we propose a set of pharmacoepidemiologic hypotheses related to recurrent VT. Of primary interest are HMG co-enzyme A reductase inhibitors (statins) and beta-adrenergic receptor blockers (beta- blockers), commonly used medications in middle-aged and elderly adults. There is accumulating evidence that statins and beta-blockers reduce pro-inflammatory cytokines and pro-coagulation hemostatic factors, leading to improved endothelial function and lower thrombotic risk. Epidemiologic evidence suggests that statins are associated with a decreased risk of incident VT but there are no data on statins or beta-blockers and VT recurrence. Our primary hypotheses are that beta-blocker therapy and statin therapy lower the risk of recurrent VT after a first event. We are also proposing several secondary aims addressing biomarkers and genetics and recurrent VT. The setting for the study is Group Health, a large integrated healthcare organization in Western Washington State where the average length of enrollment among person with incident VT has been 20.8 years. This study builds upon our previous work of VT in women to produce a cohort of 2,100 incident VT events that occurred between 2002 and 2010. Using the detailed clinical and pharmacy information collected prospectively in Group Health medical records and pharmacy files, the 2,100 male and female subjects 30-89 years of age will be followed for an average of 7 years to identify pharmacoepidemiologic risks for the development of a subsequent DVT and PE. The identification of new drugs with a demonstrated safety record that also lower the risk of recurrent VT may have clinical utility. Existing clinical trial data on statin and beta- blocker treatments are not likely to answer the question of VT recurrence and few population-based observational studies of VT have complete and unbiased assessment of statin and beta-blocker use to prospectively evaluate risk. Public Health Relevance: Little is know about factors that are associated with the recurrence of venous thrombosis. Using a population-based inception cohort of 2,100 incident venous thrombosis patients on whom we will have complete baseline and longitudinal follow-up of clinical characteristics and pharmaceutical treatments, we propose a series of pharmacoepidemiologic hypotheses related to recurrent venous thrombosis in an adult population as primary aims.

Public Health Relevance

Summary Little is know about factors that are associated with the recurrence of venous thrombosis. Using a population-based inception cohort of 2,100 incident venous thrombosis patients on whom we will have complete baseline and longitudinal follow-up of clinical characteristics and pharmaceutical treatments, we propose a series of pharmacoepidemiologic hypotheses related to recurrent venous thrombosis in an adult population as primary aims.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL095080-05
Application #
8307828
Study Section
Special Emphasis Panel (ZHL1-CSR-W (S1))
Program Officer
Link, Rebecca P
Project Start
2008-09-26
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$613,161
Indirect Cost
$106,206
Name
University of Washington
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Harrington, Laura B; Wiggins, Kerri L; Sitlani, Colleen M et al. (2016) The association of F11 genetic variants with the risk of incident venous thrombosis among women, by statin use. Thromb Haemost 115:682-4
Harrington, Laura B; Marck, Brett T; Wiggins, Kerri L et al. (2016) Cross-sectional association of endogenous steroid hormone, sex hormone-binding globulin, and precursor steroid levels with hemostatic factor levels in postmenopausal women. J Thromb Haemost :
Harrington, Laura B; Weiss, Noel S; Wiggins, Kerri L et al. (2016) Prior hysterectomy and oophorectomy and incident venous thrombosis risk among postmenopausal women: a population-based, case-control study. Menopause 23:143-9
Smith, N L; Harrington, L B; Blondon, M et al. (2016) The association of statin therapy with the risk of recurrent venous thrombosis. J Thromb Haemost 14:1384-92
Germain, Marine; Chasman, Daniel I; de Haan, Hugoline et al. (2015) Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism. Am J Hum Genet 96:532-42
Blondon, M; van Hylckama Vlieg, A; Wiggins, K L et al. (2014) Differential associations of oral estradiol and conjugated equine estrogen with hemostatic biomarkers. J Thromb Haemost 12:879-86
Smith, Nicholas L; Blondon, Marc; Wiggins, Kerri L et al. (2014) Lower risk of cardiovascular events in postmenopausal women taking oral estradiol compared with oral conjugated equine estrogens. JAMA Intern Med 174:25-31
Blondon, M; Wiggins, K L; Harrington, L B et al. (2013) Lack of strong effect modification by NFE2L2/CYP3A5/ABO of the risk of venous thrombosis associated with oral hormone therapy. J Thromb Haemost 11:1617-9
Blondon, Marc; Wiggins, Kerri L; Van Hylckama Vlieg, Astrid et al. (2013) Smoking, postmenopausal hormone therapy and the risk of venous thrombosis: a population-based, case-control study. Br J Haematol 163:418-20
Tang, Weihong; Teichert, Martina; Chasman, Daniel I et al. (2013) A genome-wide association study for venous thromboembolism: the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium. Genet Epidemiol 37:512-21

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