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.
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.
|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|
|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|
|Blondon, M; Wiggins, K L; McKnight, B et al. (2013) The association of smoking with venous thrombosis in women. A population-based, case-control study. Thromb Haemost 109:891-6|
|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|
|Smith, N L; Heit, J A; Tang, W et al. (2012) Genetic variation in F3 (tissue factor) and the risk of incident venous thrombosis: meta-analysis of eight studies. J Thromb Haemost 10:719-22|
|Smith, Nicholas L; Huffman, Jennifer E; Strachan, David P et al. (2011) Genetic predictors of fibrin D-dimer levels in healthy adults. Circulation 123:1864-72|
|Wassel, Christina L; Lange, Leslie A; Keating, Brendan J et al. (2011) Association of genomic loci from a cardiovascular gene SNP array with fibrinogen levels in European Americans and African-Americans from six cohort studies: the Candidate Gene Association Resource (CARe). Blood 117:268-75|
|Smith, Nicholas L; Rice, Kenneth M; Bovill, Edwin G et al. (2011) Genetic variation associated with plasma von Willebrand factor levels and the risk of incident venous thrombosis. Blood 117:6007-11|
|Smith, Nicholas L; Chen, Ming-Huei; Dehghan, Abbas et al. (2010) Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium. Circulation 121:1382-92|
Showing the most recent 10 out of 11 publications